Sacrosidase for use in the treatment of carbohydrate maldigestion

Abstract

The invention generally relates to methods of treating a human patient with carbohydrate maldigestion (e.g., fructan intolerance) comprising administering to the human patient, in need thereof, sacrosidase (β,D-fructofuranoside fructohydrolase).

Description

SACROSIDASE FOR USE IN THE TREATMENT OF CARBOHYDRATE MALDIGESTIONCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 612,209, filed December 19, 2023, which is hereby incorporated entirely by reference.FIELD OF THE INVENTION

[0002] The invention generally relates to methods of treating a human patient with carbohydrate maldigestion (e.g., fructan intolerance) comprising administering to the human patient, in need thereof, sacrosidase (B,D-fructofuranoside fructohydrolase).BACKGROUND OF THE INVENTION

[0003] Carbohydrate maldigestion can manifest as irritable bowel syndrome (“IBS”). Carbohydrate maldigestion can be caused by fructan intolerance that can stem from a subject’s digestive microbiome’s inability to digest complex sugars, e.g., fructans. IBS symptoms include, but are not limited to, abdominal pain, bloating, reflux, nausea, flatulence, diarrhea and / or constipation. An effective treatment for irritable bowel syndrome, such as that caused by carbohydrate maldigestion caused by fructan intolerance is still required.BRIEF SUMMARY OF THE INVENTION

[0004] Because IBS can be a manifestation of fructan intolerance, a form of carbohydrate maldigestion, methods of treating fructan intolerance and carbohydrate maldigestion are contemplated herein. In some aspects, the subject with IBS, fructan intolerance, and / or carbohydrate maldigestion was previously diagnosed with non-celiac gluten sensitivity (NCGS).

[0005] In some aspects, methods of administering sacrosidase to a subject in need thereof a single dose of about 5,000 IU to about 50,000 IU are described herein. In some aspects, the sacrosidase is administered to the subject in a total daily dosage of about 10,000 IU toabout 120,000 IU . In some aspects, the subject weighs >15 kg. In some aspects, the subject weighs <15 kg.

[0006] In some aspects, the sacrosidase is administered to the subject one or more times per day. In some aspects, the sacrosidase is administered to the subject with every meal and / or snack. In some aspects, half of dosage of the sacrosidase is administered to the subject before every meal or snack and the other half of the dosage of the sacrosidase is administered to the subject halfway through each meal or snack. In some aspects, the sacrosidase is administered orally as a solution. In some aspects, the oral solution comprising sacrosidase is diluted with a liquid prior to administration to the subject in need thereof. In further aspects, the liquid is water, milk, or infant formula. In some aspects, the liquid is cold or room temperature.

[0007] In some aspects, the subject exhibits reduced incidence and severity of gastrointestinal symptoms after administration of the sacrosidase as compared with the symptoms without administration of the sacrosidase. In some aspects, the reduced incidence and severity of gastrointestinal symptoms is determined using a Total Symptom Score. In some aspects, the reduced incidence and severity of gastrointestinal symptoms is based on a decreased incidence and severity of abdominal bloating experienced by the subject over a 24 hour period during a 7 day period in which the sacrosidase is administered.BRIEF DESCRIPTION OF THE FIGURES

[0008] Figure 1 provides results from in vitro experiments on the enzymatic ability of sacrosidase to hydrolyse glucosidic linkages within various substrates. Figure 1A provides results from an assay measuring the % hydrolysis of the a-l,P-2 glucose-fructose linkage in sucrose at after exposure to 30 or 60 lU / ml sacrosidase following 30 or 60 minutes at 50°C. Figure IB describes results from an assay measuring the % glucose observed after exposing inulin (Orafti P95) to 30, 60, 120, or 180 lU / ml sacrosidase following 30, 60, 120, or 180 minutes at 37°C. Figure 1C provides results from an assay measuring the %fructose observed after exposing inulin (Orafti P95) to 30, 60, 120, or 180 lU / ml sacrosidase following 30, 60, 120, or 180 minutes at 37°C. Figure ID provides results from an assay measuring the % hydrolysis after exposing inulin to 30, 60, 120, or 180 lU / ml sacrosidase following 30, 60, 120, or 180 minutes at 37 °C. Figure IE provides results from an assaymeasuring the % hydrolysis after exposing inulin to 30, 60, 120, or 180 lU / ml sacrosidase following 30, 60, 120, or 180 minutes at 50 °C.DETAILED DESCRIPTION OF THE INVENTIONDefinitions

[0009] So that the present disclosure can be more readily understood, certain terms are first defined. As used in this application, except as otherwise expressly provided herein, each of the following terms shall have the meaning set forth below. Additional definitions are set forth throughout the application.

[0010] Sacrosidase, also known as P,D-fructofuranoside fructohydrolase, is a glycosylated monomeric enzyme consisting of 513 amino acids, with a total molecular weight of 100,000 Da, and is commonly derived from baker’s yeast (Saccharomyces cerevisiae). The substrates for sacrosidases include carbohydrates such as sucrose or fructooligosaccharides (FOS) which comprise single glucose molecules linked to 1 or more fructose molecules by glycosidic bonds.

[0011] The term “fructans” refers to polymers that are comprised of 1 molecule of glucose linked to 2 or more molecules of fructose by glycosidic bonds. These glycosidic bonds typically occur at one of two hydroxyl linkage sites of the fructose molecules (a-l,P-2 or a-6,P-2). For the purposes of this application, fructans will concentrate on the a-l,P-2 linkage site.

[0012] The term “fructo-oligosaccharides (FOS)” refers to fructans that are comprised of 1 molecule of glucose linked to 2-9 molecules of fructose by glycosidic bonds. A general chemical structure for FOS molecules is the following formula,wherein the value for n is an integer between 0 and 7.

[0013] “Carbohydrate maldigestion” refers to various disorders due to reduced ability to cleave complex sugars.

[0014] “Fructan intolerance” is a form of carbohydrate maldigestion caused by the reduced ability to digest fructans.Methods of Treatment

[0015] Methods of treating subjects having irritable bowel syndrome, a form of carbohydrate maldigestion that can be caused by fructan intolerance, comprising administering sacrosidase to the subject in need thereof are provided herein. Also disclosed herein are methods of treating subjects having carbohydrate maldigestion, as well as methods of treating subjects having fructan intolerance. In some aspects, the subject treated in each of the methods described herein was previously diagnosed with NGCS. In some aspects, the subject with irritable bowel syndrome has irritable bowel syndrome with constipation (IBS-C), irritable bowel syndrome with diarrhea (IBS-D), or irritable bowel syndrome with mixed constipation and diarrhea (IBS-M).

[0016] In some aspects, the methods described herein comprise administering sacrosidase to the subject in need thereof a single dose of about 5,000 IU to about 50,000. In some aspects, the methods comprise administering sacrosidase to the subject in need thereof a single dose of about 5,000 IU to about 45,000 IU, about 5,000 IU to about 40,000 IU, about 5,000 IU to about 35,000 IU, about 5,000 IU to about 30,000 IU, about 5,000 IU to about 25,000 IU, about 5,000 IU to about 20,000 IU, about 5,000 IU to about 15,000 IU, about 5,000 IU to about 10,000 IU, about 10,000 IU to about 50,000 IU, about 10,000 IU to about 45,000 IU, about 10,000 IU to about 40,000 IU, about 10,000 IU to about 35,000 IU, about 10,000 IU to about 30,000 IU, about 10,000 IU to about 25,000 IU, about 10,000 IU to about 20,000 IU, about 10,000 IU to about 15,000 IU, about 15,000 IU to about 50,000 IU, about 15,000 IU to about 45,000 IU, about 15,000 IU to about 40,000 IU, about 15,000 IU to about 35,000 IU, about 15,000 IU to about 30,000 IU, about 15,000 IU to about 25,000 IU, about 15,000 IU to about 20,000 IU, about 20,000 IU to about 50,000 IU, about 20,000 IU to about 45,000 IU, about 20,000 IU to about 40,000 IU, about 20,000 IU to about 35,000 IU, about 20,000 IU to about 30,000 IU, about 20,000 IU to about 25,000 IU, about 25,000 IU to about 50,000 IU, about 25,000 IU to about 45,000 IU, about 25,000 IU to about 40,000 IU, about 25,000 IU to about 35,000 IU, about 25,000 IU to about 30,000 IU,about 30,000 IU to about 50,000 IU, about 30,000 IU to about 45,000 IU, about 30,000 IU to about 40,000 IU, about 30,000 IU to about 35,000 IU, about 35,000 IU to about 50,000 IU, about 35,000 IU to about 45,000 IU, about 35,000 IU to about 40,000 IU, about 40,000 IU to about 50,000 IU, about 40,000 IU to about 45,000 IU, or about 45,000 IU to about 50,000 IU. In some aspects, the methods comprise administering sacrosidase to the subject in a dose of about 5,000 IU, about 5,500 IU, about 6,000 IU, about 6,500 IU, about 7,000 IU, about 7,500 IU, about 8,000 IU, about 8,500 IU, about 9,000 IU, about 9,500 IU, 10,000 IU, about 10,500 IU, about 11,000 IU, about 11,500 IU, about 12,000 IU, about 12,500 IU, about 13,000 IU, about 13,500 IU, about 14,000 IU, about 14,500 IU, about 15,000 IU, about 15,500 IU, about 16,000 IU, about 16,500 IU, about 17,000 IU, about 17,500 IU, about 18,000 IU, about 18,500 IU, about 19,000 IU, about 19,500 IU, about 20,000 IU, about 20,500 IU, about 21,000 IU, about 21,500 IU, about 22,000 IU, about 22,500 IU, about 23,000 IU, about 23,500 IU, about 24,000 IU, about 24,500 IU, about 25,000 IU, about 25,500 IU, about 26,000 IU, about 26,500 IU, about 27,000 IU, about 27,500 IU, about 28,000 IU, about 28,500 IU, about 29,000 IU, about 29,500 IU, about 30,000 IU, about 30,500 IU, about 31,000 IU, about 31,500 IU, about 32,000 IU, about 32,500 IU, about 33,000 IU, about 33,500 IU, about 34,000 IU, about 34,500 IU, about 35,000 IU, about 35,500 IU, about 36,000 IU, about 36,500 IU, about 37,000 IU, about 37,500 IU, about 38,000 IU, about 38,500 IU, about 39,000 IU, about 39,500 IU, about 40,000 IU, about 40,500 IU, about 41,000 IU, about 41,500 IU, about 42,000 IU, about 42,500 IU, about 43,000 IU, about 43,500 IU, about 44,000 IU, about 44,500 IU, about 45,000 IU, about 45,500 IU, about 46,000 IU, about 46,500 IU, about 47,000 IU, about 47,500 IU, about 48,000 IU, about 48,500 IU, about 49,000 IU, about 49,500, IU or about 50,000 IU.

[0017] In some aspects, the methods described herein comprise administering sacrosidase to the subject in need thereof a single dose of about 5,000 IU to about 10,000 IU. In some aspects, the methods described herein comprise administering sacrosidase to the subject in need thereof a single dose of about 8,750 IU.

[0018] In some aspects, the methods described herein comprise administering sacrosidase to the subject in need thereof a single dose of about 10,000 IU to about 50,000 IU. In some aspects, the methods described herein comprise administering sacrosidase to the subject in need thereof a single dose about 17,000 IU or about 34,000 IU. In some aspects, the methods described herein comprise administering sacrosidase to the subject in need thereofa single dose of about 17,000 IU. In another aspect, the methods described herein comprise administering sacrosidase to the subject in need thereof a single dose of about 25,500 IU. In still another aspect, the methods described herein comprise administering sacrosidase to the subject in need thereof a single dose of about 34,000 IU.

[0019] In some aspects, the methods described herein comprise administering a single dose of sacrosidase to the subject in need thereof one or more times per day. In some aspects, the methods described herein comprise administering a single dose of sacrosidase to the subject in need thereof one, two, three, four, or more times per day. In some aspects, the methods described herein comprise administering a single dose of sacrosidase to the subject in need thereof with each meal. In some aspects, the methods described herein comprise administering a single dose of sacrosidase to the subject in need thereof with each snack. In some aspects, the methods described herein comprise administering a single dose of sacrosidase to the subject in need thereof with every meal or snack. In some aspects, the methods described herein comprise administering a single dose of sacrosidase to the subject in need thereof with every meal and snack.

[0020] In some aspects, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 10,000 IU to about 50,000 IU one or more times per day. In some aspects, the methods comprise administering the sacrosidase to the subject in need thereof a single dose of about 11,000 IU to about 49,000 IU, about 12,000 IU to about 48,000 IU, about 13,000 IU to about 47,000 IU, about 14,000 IU to about 46,000 IU, about 15,000 IU to about 45,000 IU, about 16,000 IU to about 44,000 IU, about 17,000 IU to about 43,000 IU, about 17,000 IU to about 42,000 IU, about 17,000 IU to about 41,000 IU, about 19,000 IU to about 40,000 IU, about 17,000 IU to about 39,000 IU, or about 17,000 IU to about 38,000 IU one or more times per day. In certain aspects, the methods comprise administering the sacrosidase to the subject as a single dose of about 10,000 IU, about 10,500 IU, about 11,000 IU, about 11,500 IU, about 12,000 IU, about 12,500 IU, about 13,000 IU, about 13,500 IU, about 14,000 IU, about14.500 IU, about 15,000 IU, about 15,500 IU, about 16,000 IU, about 16,500 IU, about17,000 IU, about 17,500 IU, about 18,000 IU, about 18,500 IU, about 19,000 IU, about19.500 IU, about 20,000 IU, about 20,500 IU, about 21,000 IU, about 21,500 IU, about22,000 IU, about 22,500 IU, about 23,000 IU, about 23,500 IU, about 24,000 IU, about24.500 IU, about 25,000 IU, about 25,500 IU, about 26,000 IU, about 26,500 IU, about27,000 IU, about 27,500 IU, about 28,000 IU, about 28,500 IU, about 29,000 IU, about29.500 IU, about 30,000 IU, about 30,500 IU, about 31,000 IU, about 31,500 IU, about32,000 IU, about 32,500 IU, about 33,000 IU, about 33,500 IU, about 34,000 IU, about34.500 IU, about 35,000 IU, about 35,500 IU, about 36,000 IU, about 36,500 IU, about37,000 IU, about 37,500 IU, about 38,000 IU, about 38,500 IU, about 39,000 IU, about39.500 IU, about 40,000 IU, about 40,500 IU, about 41,000 IU, about 41,500 IU, about42,000 IU, about 42,500 IU, about 43,000 IU, about 43,500 IU, about 44,000 IU, about44.500 IU, about 45,000 IU, about 45,500 IU, about 46,000 IU, about 46,500 IU, about47,000 IU, about 47,500 IU, about 48,000 IU, about 48,500 IU, about 49,000 IU, about49,500, IU or about 50,000 IU one or more times per day. In one aspect, the methods comprise administering the sacrosidase to the subject in need thereof a single dose of about 17,000 IU or about 34,000 IU one or more times per day. In one aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 17,000 IU one or more times per day. In another aspect, the methods described herein comprise administering sacrosidase to the subject in need thereof a single dose of about 25,500 IU one or more times per day. In yet another aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 34,000 IU one or more times per day.

[0021] In some aspects, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 10,000 IU to about 50,000 IU one, two, three, four, or more times per day. In some aspects, the methods comprise administering the sacrosidase to the subject in need thereof a single dose of about 11,000 IU to about 49,000 IU, about 12,000 IU to about 48,000 IU, about 13,000 IU to about 47,000 IU, about 14,000 IU to about 46,000 IU, about 15,000 IU to about 45,000 IU, about 16,000 IU to about 44,000 IU, about 17,000 IU to about 43,000 IU, about 17,000 IU to about 42,000 IU, about 17,000 IU to about 41,000 IU, about 19,000 IU to about 40,000 IU, about 17,000 IU to about 39,000 IU, or about 17,000 IU to about 38,000 IU one, two, three, four, or more times per day. In certain aspects, the methods comprise administering the sacrosidase to the subject as a single dose of about 10,000 IU, about 10,500 IU, about11,000 IU, about 11,500 IU, about 12,000 IU, about 12,500 IU, about 13,000 IU, about13.500 IU, about 14,000 IU, about 14,500 IU, about 15,000 IU, about 15,500 IU, about16,000 IU, about 16,500 IU, about 17,000 IU, about 17,500 IU, about 18,000 IU, about18.500 IU, about 19,000 IU, about 19,500 IU, about 20,000 IU, about 20,500 IU, about21,000 IU, about 21,500 IU, about 22,000 IU, about 22,500 IU, about 23,000 IU, about23.500 IU, about 24,000 IU, about 24,500 IU, about 25,000 IU, about 25,500 IU, about26,000 IU, about 26,500 IU, about 27,000 IU, about 27,500 IU, about 28,000 IU, about28.500 IU, about 29,000 IU, about 29,500 IU, about 30,000 IU, about 30,500 IU, about31,000 IU, about 31,500 IU, about 32,000 IU, about 32,500 IU, about 33,000 IU, about33.500 IU, about 34,000 IU, about 34,500 IU, about 35,000 IU, about 35,500 IU, about36,000 IU, about 36,500 IU, about 37,000 IU, about 37,500 IU, about 38,000 IU, about38.500 IU, about 39,000 IU, about 39,500 IU, about 40,000 IU, about 40,500 IU, about41,000 IU, about 41,500 IU, about 42,000 IU, about 42,500 IU, about 43,000 IU, about43.500 IU, about 44,000 IU, about 44,500 IU, about 45,000 IU, about 45,500 IU, about46,000 IU, about 46,500 IU, about 47,000 IU, about 47,500 IU, about 48,000 IU, about48.500 IU, about 49,000 IU, about 49,500, IU or about 50,000 IU one, two, three, four, or more times per day. In one aspect, the methods comprise administering the sacrosidase to the subject in need thereof a single dose of about 17,000 IU or about 34,000 IU one, two, three, four, or more times per day. In one aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 17,000 IU one, two, three, four, or more times per day. In another aspect, the methods described herein comprise administering sacrosidase to the subject in need thereof a single dose of about 25,500 IU one, two, three, four, or more times per day. In yet another aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 34,000 IU one, two, three, four, or more times per day.

[0022] In some aspects, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 10,000 IU to about 50,000 IU with each meal. In some aspects, the methods comprise administering the sacrosidase to the subject in need thereof a single dose of about 11,000 IU to about 49,000 IU, about 12,000 IU to about 48,000 IU, about 13,000 IU to about 47,000 IU, about 14,000 IU to about 46,000 IU, about 15,000 IU to about 45,000 IU, about 16,000 IU to about 44,000 IU, about 17,000 IU to about 43,000 IU, about 17,000 IU to about 42,000 IU, about 17,000 IU to about 41,000 IU, about 19,000 IU to about 40,000 IU, about 17,000 IU to about 39,000 IU, or about 17,000 IU to about 38,000 IU with each meal. In certain aspects, the methods comprise administering the sacrosidase to the subject as a single dose of about 10,000 IU,about 10,500 IU, about 11,000 IU, about 11,500 IU, about 12,000 IU, about 12,500 IU, about 13,000 IU, about 13,500 IU, about 14,000 IU, about 14,500 IU, about 15,000 IU, about 15,500 IU, about 16,000 IU, about 16,500 IU, about 17,000 IU, about 17,500 IU, about 18,000 IU, about 18,500 IU, about 19,000 IU, about 19,500 IU, about 20,000 IU, about 20,500 IU, about 21,000 IU, about 21,500 IU, about 22,000 IU, about 22,500 IU, about 23,000 IU, about 23,500 IU, about 24,000 IU, about 24,500 IU, about 25,000 IU, about 25,500 IU, about 26,000 IU, about 26,500 IU, about 27,000 IU, about 27,500 IU, about 28,000 IU, about 28,500 IU, about 29,000 IU, about 29,500 IU, about 30,000 IU, about 30,500 IU, about 31,000 IU, about 31,500 IU, about 32,000 IU, about 32,500 IU, about 33,000 IU, about 33,500 IU, about 34,000 IU, about 34,500 IU, about 35,000 IU, about 35,500 IU, about 36,000 IU, about 36,500 IU, about 37,000 IU, about 37,500 IU, about 38,000 IU, about 38,500 IU, about 39,000 IU, about 39,500 IU, about 40,000 IU, about 40,500 IU, about 41,000 IU, about 41,500 IU, about 42,000 IU, about 42,500 IU, about 43,000 IU, about 43,500 IU, about 44,000 IU, about 44,500 IU, about 45,000 IU, about 45,500 IU, about 46,000 IU, about 46,500 IU, about 47,000 IU, about 47,500 IU, about 48,000 IU, about 48,500 IU, about 49,000 IU, about 49,500, IU or about 50,000 IU with each meal. In one aspect, the methods comprise administering the sacrosidase to the subject in need thereof a single dose of about 17,000 IU or about 34,000 IU with each meal. In one aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 17,000 IU with each meal. In another aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 25,500 IU with each meal. In yet another aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 34,000 IU with each meal.

[0023] In some aspects, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 10,000 IU to about 50,000 IU with each snack. In some aspects, the methods comprise administering the sacrosidase to the subject in need thereof a single dose of about 11,000 IU to about 49,000 IU, about 12,000 IU to about 48,000 IU, about 13,000 IU to about 47,000 IU, about 14,000 IU to about 46,000 IU, about 15,000 IU to about 45,000 IU, about 16,000 IU to about 44,000 IU, about 17,000 IU to about 43,000 IU, about 17,000 IU to about 42,000 IU, about 17,000 IU to about 41,000 IU, about 19,000 IU to about 40,000 IU, about 17,000 IU to about 39,000IU, or about 17,000 IU to about 38,000 IU with each snack. In certain aspects, the methods comprise administering the sacrosidase to the subject as a single dose of about 10,000 IU, about 10,500 IU, about 11,000 IU, about 11,500 IU, about 12,000 IU, about 12,500 IU, about 13,000 IU, about 13,500 IU, about 14,000 IU, about 14,500 IU, about 15,000 IU, about 15,500 IU, about 16,000 IU, about 16,500 IU, about 17,000 IU, about 17,500 IU, about 18,000 IU, about 18,500 IU, about 19,000 IU, about 19,500 IU, about 20,000 IU, about 20,500 IU, about 21,000 IU, about 21,500 IU, about 22,000 IU, about 22,500 IU, about 23,000 IU, about 23,500 IU, about 24,000 IU, about 24,500 IU, about 25,000 IU, about 25,500 IU, about 26,000 IU, about 26,500 IU, about 27,000 IU, about 27,500 IU, about 28,000 IU, about 28,500 IU, about 29,000 IU, about 29,500 IU, about 30,000 IU, about 30,500 IU, about 31,000 IU, about 31,500 IU, about 32,000 IU, about 32,500 IU, about 33,000 IU, about 33,500 IU, about 34,000 IU, about 34,500 IU, about 35,000 IU, about 35,500 IU, about 36,000 IU, about 36,500 IU, about 37,000 IU, about 37,500 IU, about 38,000 IU, about 38,500 IU, about 39,000 IU, about 39,500 IU, about 40,000 IU, about 40,500 IU, about 41,000 IU, about 41,500 IU, about 42,000 IU, about 42,500 IU, about 43,000 IU, about 43,500 IU, about 44,000 IU, about 44,500 IU, about 45,000 IU, about 45,500 IU, about 46,000 IU, about 46,500 IU, about 47,000 IU, about 47,500 IU, about 48,000 IU, about 48,500 IU, about 49,000 IU, about 49,500 IU or about 50,000 IU with each snack. In one aspect, the methods comprise administering the sacrosidase to the subject in need thereof a single dose of about 17,000 IU or about 34,000 IU with each snack. In one aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 17,000 IU with each snack. In another aspect, the methods described herein comprise administering sacrosidase to the subject in need thereof a single dose of about 25,500 IU with each snack. In yet another aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 34,000 IU with each snack.

[0024] In some aspects, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 10,000 IU to about 50,000 IU with each meal or snack. In some aspects, the methods comprise administering the sacrosidase to the subject in need thereof a single dose of about 11,000 IU to about 49,000 IU, about 12,000 IU to about 48,000 IU, about 13,000 IU to about 47,000 IU, about 14,000 IU to about 46,000 IU, about 15,000 IU to about 45,000 IU, about 16,000 IU to about44,000 IU, about 17,000 IU to about 43,000 IU, about 17,000 IU to about 42,000 IU, about 17,000 IU to about 41,000 IU, about 19,000 IU to about 40,000 IU, about 17,000 IU to about 39,000 IU, or about 17,000 IU to about 38,000 IU with each meal or snack. In certain aspects, the methods comprise administering the sacrosidase to the subject as a single dose of about 10,000 IU, about 10,500 IU, about 11,000 IU, about 11,500 IU, about 12,000 IU, about 12,500 IU, about 13,000 IU, about 13,500 IU, about 14,000 IU, about 14,500 IU, about 15,000 IU, about 15,500 IU, about 16,000 IU, about 16,500 IU, about 17,000 IU, about 17,500 IU, about 18,000 IU, about 18,500 IU, about 19,000 IU, about 19,500 IU, about 20,000 IU, about 20,500 IU, about 21,000 IU, about 21,500 IU, about 22,000 IU, about 22,500 IU, about 23,000 IU, about 23,500 IU, about 24,000 IU, about 24,500 IU, about 25,000 IU, about 25,500 IU, about 26,000 IU, about 26,500 IU, about 27,000 IU, about 27,500 IU, about 28,000 IU, about 28,500 IU, about 29,000 IU, about 29,500 IU, about 30,000 IU, about 30,500 IU, about 31,000 IU, about 31,500 IU, about 32,000 IU, about 32,500 IU, about 33,000 IU, about 33,500 IU, about 34,000 IU, about 34,500 IU, about 35,000 IU, about 35,500 IU, about 36,000 IU, about 36,500 IU, about 37,000 IU, about 37,500 IU, about 38,000 IU, about 38,500 IU, about 39,000 IU, about 39,500 IU, about 40,000 IU, about 40,500 IU, about 41,000 IU, about 41,500 IU, about 42,000 IU, about 42,500 IU, about 43,000 IU, about 43,500 IU, about 44,000 IU, about 44,500 IU, about 45,000 IU, about 45,500 IU, about 46,000 IU, about 46,500 IU, about 47,000 IU, about 47,500 IU, about 48,000 IU, about 48,500 IU, about 49,000 IU, about 49,500 IU or about 50,000 IU with each snack. In one aspect, the methods comprise administering the sacrosidase to the subject in need thereof a single dose of about 17,000 IU or about 34,000 IU with each meal or snack. In one aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 17,000 IU with each meal or snack. In another aspect, the methods described herein comprise administering sacrosidase to the subject in need thereof a single dose of about 25,500 IU with each meal or snack. In yet another aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 34,000 IU with each meal or snack.

[0025] In some aspects, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 10,000 IU to about 50,000 IU with each meal and snack. In some aspects, the methods comprise administering thesacrosidase to the subject in need thereof a single dose of about 11,000 IU to about 49,000 IU, about 12,000 IU to about 48,000 IU, about 13,000 IU to about 47,000 IU, about 14,000 IU to about 46,000 IU, about 15,000 IU to about 45,000 IU, about 16,000 IU to about 44,000 IU, about 17,000 IU to about 43,000 IU, about 17,000 IU to about 42,000 IU, about 17,000 IU to about 41,000 IU, about 19,000 IU to about 40,000 IU, about 17,000 IU to about 39,000 IU, or about 17,000 IU to about 38,000 IU with each meal or snack. In certain aspects, the methods comprise administering the sacrosidase to the subject as a single dose of about 10,000 IU, about 10,500 IU, about 11,000 IU, about 11,500 IU, about 12,000 IU, about 12,500 IU, about 13,000 IU, about 13,500 IU, about 14,000 IU, about 14,500 IU, about 15,000 IU, about 15,500 IU, about 16,000 IU, about 16,500 IU, about 17,000 IU, about 17,500 IU, about 18,000 IU, about 18,500 IU, about 19,000 IU, about 19,500 IU, about 20,000 IU, about 20,500 IU, about 21,000 IU, about 21,500 IU, about 22,000 IU, about 22,500 IU, about 23,000 IU, about 23,500 IU, about 24,000 IU, about 24,500 IU, about 25,000 IU, about 25,500 IU, about 26,000 IU, about 26,500 IU, about 27,000 IU, about 27,500 IU, about 28,000 IU, about 28,500 IU, about 29,000 IU, about 29,500 IU, about 30,000 IU, about 30,500 IU, about 31,000 IU, about 31,500 IU, about 32,000 IU, about 32,500 IU, about 33,000 IU, about 33,500 IU, about 34,000 IU, about 34,500 IU, about 35,000 IU, about 35,500 IU, about 36,000 IU, about 36,500 IU, about 37,000 IU, about 37,500 IU, about 38,000 IU, about 38,500 IU, about 39,000 IU, about 39,500 IU, about 40,000 IU, about 40,500 IU, about 41,000 IU, about 41,500 IU, about 42,000 IU, about 42,500 IU, about 43,000 IU, about 43,500 IU, about 44,000 IU, about 44,500 IU, about 45,000 IU, about 45,500 IU, about 46,000 IU, about 46,500 IU, about 47,000 IU, about 47,500 IU, about 48,000 IU, about 48,500 IU, about 49,000 IU, about 49,500 IU or about 50,000 IU with each snack. In one aspect, the methods comprise administering the sacrosidase to the subject in need thereof a single dose of about 17,000 IU or about 34,000 IU with each meal and snack. In one aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 17,000 IU with each meal and snack. In another aspect, the methods described herein comprise administering sacrosidase to the subject in need thereof a single dose of about 25,500 IU with each meal and snack. In yet another aspect, the methods described herein comprise administering the sacrosidase to the subject in need thereof a single dose of about 34,000 IU with each meal and snack.

[0026] In some aspects, half of the dosage of the sacrosidase is administered at the beginning of each meal and the other half of the dosage of the sacrosidase is administered during each meal. In some aspects, half of the dosage of the sacrosidase is administered at the beginning of each meal and the other half of the dosage of the sacrosidase is administered after each meal. In some aspects, half of the dosage of the sacrosidase is administered at the beginning of each snack and the other half of the dosage of the sacrosidase is administered during each snack. In some aspects, half of the dosage of the sacrosidase is administered at the beginning of each snack and the other half of the dosage of the sacrosidase is administered after each snack. In some aspects, half of the dosage of the sacrosidase is administered at the beginning of each meal or snack and the other half of the dosage of the sacrosidase is administered during each meal or snack. In some aspects, half of the dosage of the sacrosidase is administered at the beginning of each meal or snack and the other half of the dosage of the sacrosidase is administered after each meal or snack. In some aspects, half of the dosage of the sacrosidase is administered at the beginning of each meal and snack and the other half of the dosage of the sacrosidase is administered during each meal and snack. In some aspects, half of the dosage of the sacrosidase is administered at the beginning of each meal and snack and the other half of the dosage of the sacrosidase is administered after each meal and snack.

[0027] In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each meal and about 8,500 IU of the sacrosidase is administered during each meal. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each meal and about 8,500 IU of the sacrosidase is administered after each meal. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each snack and about 8,500 IU of the sacrosidase is administered during each snack. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each snack and about 8,500 IU of the sacrosidase is administered after each snack. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each meal or snack and about 8,500 IU of the sacrosidase is administered during each meal or snack. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each meal or snack and about 8,500 IU of the sacrosidase is administered after each meal or snack. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each meal and snack and about 8,500 IU of the sacrosidase is administered during each meal and snack. In some aspects,about 8,500 IU of the sacrosidase is administered at the beginning of each meal and snack and about 8,500 IU of the sacrosidase is administered after each meal and snack.

[0028] In some aspects, two-thirds of the dosage of the sacrosidase is administered at the beginning of each meal and one-third of the dosage of the sacrosidase is administered during each meal. In some aspects, two-thirds of the dosage of the sacrosidase is administered at the beginning of each meal and one-third of the dosage of the sacrosidase is administered after each meal. In some aspects, two-thirds of the dosage of the sacrosidase is administered at the beginning of each snack and one-third of the dosage of the sacrosidase is administered during each snack. In some aspects, two-thirds the dosage of the sacrosidase is administered at the beginning of each snack and one-third of the dosage of the sacrosidase is administered after each snack. In some aspects, two-thirds of the dosage of the sacrosidase is administered at the beginning of each meal or snack and one-third of the dosage of the sacrosidase is administered during each meal or snack. In some aspects, two- thirds of the dosage of the sacrosidase is administered at the beginning of each meal or snack and one-third of the dosage of the sacrosidase is administered after each meal or snack. In some aspects, two-thirds of the dosage of the sacrosidase is administered at the beginning of each meal and snack and one-third of the dosage of the sacrosidase is administered during each meal and snack. In some aspects, two-thirds of the dosage of the sacrosidase is administered at the beginning of each meal and snack and one-third of the dosage of the sacrosidase is administered after each meal and snack.

[0029] In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each meal and two-thirds of the dosage of the sacrosidase is administered during each meal. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each meal and two-thirds of the dosage of the sacrosidase is administered after each meal. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each snack and two-thirds of the dosage of the sacrosidase is administered during each snack. In some aspects, one-third the dosage of the sacrosidase is administered at the beginning of each snack and two-thirds of the dosage of the sacrosidase is administered after each snack. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each meal or snack and two-thirds of the dosage of the sacrosidase is administered during each meal or snack. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each meal orsnack and two-thirds of the dosage of the sacrosidase is administered after each meal or snack. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each meal and snack and two-thirds of the dosage of the sacrosidase is administered during each meal and snack. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each meal and snack and two-thirds of the dosage of the sacrosidase is administered after each meal and snack.

[0030] In some aspects, about 17,000 IU of the sacrosidase is administered at the beginning of each meal and about 8,500 IU of the sacrosidase is administered during each meal. In some aspects, about 17,000 IU of the sacrosidase is administered at the beginning of each meal and about 8,500 IU of the sacrosidase is administered after each meal. In some aspects, about 17,000 IU of the sacrosidase is administered at the beginning of each snack and about 8,500 IU of the sacrosidase is administered during each snack. In some aspects, about 17,000 IU of the sacrosidase is administered at the beginning of each snack and about 8,500 IU of the sacrosidase is administered after each snack. In some aspects, about 17,000 IU of the sacrosidase is administered at the beginning of each meal or snack and about 8,500 IU of the sacrosidase is administered during each meal or snack. In some aspects, about 17,000 IU of the sacrosidase is administered at the beginning of each meal or snack and about 8,500 IU of the sacrosidase is administered after each meal or snack. In some aspects, about 17,000 IU of the sacrosidase is administered at the beginning of each meal and snack and about 8,500 IU of the sacrosidase is administered during each meal and snack. In some aspects, about 17,000 IU of the sacrosidase is administered at the beginning of each meal and snack and about 8,500 IU of the sacrosidase is administered after each meal and snack.

[0031] In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each meal and two-thirds of the dosage of the sacrosidase is administered during each meal. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each meal and two-thirds of the dosage of the sacrosidase is administered after each meal. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each snack and two-thirds of the dosage of the sacrosidase is administered during each snack. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each snack and two-thirds of the dosage of the sacrosidase is administered after each snack. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each meal or snack and two-thirds ofthe dosage of the sacrosidase is administered during each meal or snack. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each meal or snack and two-thirds of the dosage of the sacrosidase is administered after each meal or snack. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each meal and snack and two-thirds of the dosage of the sacrosidase is administered during each meal and snack. In some aspects, one-third of the dosage of the sacrosidase is administered at the beginning of each meal and snack and two-thirds of the dosage of the sacrosidase is administered after each meal and snack.

[0032] In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each meal and about 17,000 IU of the sacrosidase is administered during each meal. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each meal and about 17,000 IU of the sacrosidase is administered after each meal. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each snack and about 17,000 IU of the sacrosidase is administered during each snack. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each snack and about 17,000 IU of the sacrosidase is administered after each snack. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each meal or snack and about 17,000 IU of the sacrosidase is administered during each meal or snack. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each meal or snack and about 17,000 IU of the sacrosidase is administered after each meal or snack. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each meal and snack and about 17,000 IU of the sacrosidase is administered during each meal and snack. In some aspects, about 8,500 IU of the sacrosidase is administered at the beginning of each meal and snack and about 17,000 IU of the sacrosidase is administered after each meal and snack.

[0033] In some aspects, the methods described herein comprise administering the sacrosidase to the subject in a total daily dosage of about 10,000 IU to about 120,000 IU. In some aspects, the methods described herein comprise administering the sacrosidase to the subject in a total daily dosage of about 10,000 IU to about 110,000 IU, about 10,000 IU to about 100,000 IU, about 10,000 IU to about 90,000 IU, about 10,000 IU to about 85,000 IU, about 10,000 IU to about 80,000 IU, about 10,000 IU to about 75,000 IU, about 10,000 IU to about 70,000 IU, about 10,000 IU to about 65,000 IU, about 10,000 IU to about60,000 IU, about 10,000 IU to about 55,000 IU, about 10,000 IU to about 50,000 IU, about 10,000 IU to about 45,000 IU, about 10,000 IU to about 40,000 IU, about 10,000 IU to about 35,000 IU, about 10,000 IU to about 30,000 IU, about 10,000 IU to about 25,000 IU, about 10,000 IU to about 20,000 IU, about 10,000 IU to about 15,000 IU, about 15,000 IU to about 120,000 IU, about 15,000 IU to about 110,000 IU, about 15,000 IU to about 100,000 IU, about 15,000 IU to about 90,000 IU, about 15,000 IU to about 85,000 IU, about 15,000 IU to about 80,000 IU, about 15,000 IU to about 75,000 IU, about 15,000 IU to about 70,000 IU, about 15,000 IU to about 65,000 IU, about 15,000 IU to about 60,000 IU, about 15,000 IU to about 55,000 IU, about 15,000 IU to about 50,000 IU, about 15,000 IU to about 45,000 IU, about 15,000 IU to about 40,000 IU, about 15,000 IU to about 35,000 IU, about 15,000 IU to about 30,000 IU, about 15,000 IU to about 25,000 IU, about 15,000 IU to about 20,000 IU, about 20,000 IU to about 120,000 IU, about 20,000 IU to about 110,000 IU, about 20,000 IU to about 100,000 IU, about 20,000 IU to about 90,000 IU, about 20,000 IU to about 85,000 IU, about 20,000 IU to about 80,000 IU, about 20,000 IU to about 75,000 IU, about 20,000 IU to about 70,000 IU, about 20,000 IU to about 65,000 IU, about 20,000 IU to about 60,000 IU, about 20,000 IU to about 55,000 IU, about 20,000 IU to about 50,000 IU, about 20,000 IU to about 45,000 IU, about 20,000 IU to about 40,000 IU, about 20,000 IU to about 35,000 IU, about 20,000 IU to about 30,000 IU, about 20,000 IU to about 25,000 IU, about 25,000 IU to about 120,000 IU, about 25,000 IU to about 110,000 IU, about 25,000 IU to about 100,000 IU, about 25,000 IU to about 90,000 IU, about 25,000 IU to about 85,000 IU, about 25,000 IU to about 80,000 IU, about 25,000 IU to about 75,000 IU, about 25,000 IU to about 70,000 IU, about 25,000 IU to about 65,000 IU, about 25,000 IU to about 60,000 IU, about 25,000 IU to about 55,000 IU, about 25,000 IU to about 50,000 IU, about 25,000 IU to about 45,000 IU, about 25,000 IU to about 40,000 IU, about 25,000 IU to about 35,000 IU, about 25,000 IU to about 30,000 IU, about 30,000 IU to about 120,000 IU, about 30,000 IU to about 110,000 IU, about 30,000 IU to about 100,000 IU, about 30,000 IU to about 90,000 IU, about 30,000 IU to about 85,000 IU, about 30,000 IU to about 80,000 IU, about 30,000 IU to about 75,000 IU, about 30,000 IU to about 70,000 IU, about 30,000 IU to about 65,000 IU, about 30,000 IU to about 60,000 IU, about 30,000 IU to about 55,000 IU, about 30,000 IU to about 50,000 IU, about 30,000 IU to about 45,000 IU, about 30,000 IU to about 40,000 IU, about 30,000 IU to about 35,000 IU, about 35,000 IU to about 120,000 IU, about 35,000 IU to about 110,000IU, about 35,000 IU to about 100,000 IU, about 35,000 IU to about 90,000 IU, about 35,000 IU to about 85,000 IU, about 35,000 IU to about 80,000 IU, about 35,000 IU to about 75,000 IU, about 35,000 IU to about 70,000 IU, about 35,000 IU to about 65,000 IU, about 35,000 IU to about 60,000 IU, about 35,000 IU to about 55,000 IU, about 35,000 IU to about 50,000 IU, about 35,000 IU to about 45,000 IU, about 35,000 IU to about 40,000 IU, about 40,000 IU to about 120,000 IU, about 40,000 IU to about 110,000 IU, about 40,000 IU to about 100,000 IU, about 40,000 IU to about 90,000 IU, about 40,000 IU to about 85,000 IU, about 40,000 IU to about 80,000 IU, about 40,000 IU to about 75,000 IU, about 40,000 IU to about 70,000 IU, about 40,000 IU to about 65,000 IU, about 40,000 IU to about 60,000 IU, about 40,000 IU to about 55,000 IU, about 40,000 IU to about 50,000 IU, about 40,000 IU to about 45,000 IU, about 45,000 IU to about 120,000 IU, about 45,000 IU to about 110,000 IU, about 45,000 IU to about 100,000 IU, about 45,000 IU to about 90,000 IU, about 45,000 IU to about 85,000 IU, about 45,000 IU to about 80,000 IU, about 45,000 IU to about 75,000 IU, about 45,000 IU to about 70,000 IU, about 45,000 IU to about 65,000 IU, about 45,000 IU to about 60,000 IU, about 45,000 IU to about 55,000 IU, about 45,000 IU to about 50,000 IU, about 50,000 IU to about 120,000 IU, about 50,000 IU to about 110,000 IU, about 50,000 IU to about 100,000 IU, about 50,000 IU to about 90,000 IU, about 50,000 IU to about 85,000 IU, about 50,000 IU to about 80,000 IU, about 50,000 IU to about 75,000 IU, about 50,000 IU to about 70,000 IU, about 50,000 IU to about 65,000 IU, about 50,000 IU to about 60,000 IU, about 50,000 IU to about 55,000 IU, about 55,000 IU to about 120,000 IU, about 55,000 IU to about 110,000 IU, about 55,000 IU to about 100,000 IU, about 55,000 IU to about 90,000 IU, about 55,000 IU to about 85,000 IU, about 55,000 IU to about 80,000 IU, about 55,000 IU to about 75,000 IU, about 55,000 IU to about 70,000 IU, about 55,000 IU to about 65,000 IU, about 55,000 IU to about 60,000 IU, about 60,000 IU to about 120,000 IU, about 60,000 IU to about 110,000 IU, about 60,000 IU to about 100,000 IU, about 60,000 IU to about 90,000 IU, about 60,000 IU to about 85,000 IU, about 60,000 IU to about 80,000 IU, about 60,000 IU to about 75,000 IU, about 60,000 IU to about 70,000 IU, about 60,000 IU to about 65,000 IU, about 65,000 IU to about 120,000 IU, about 65,000 IU to about 110,000 IU, about 65,000 IU to about 100,000 IU, about 65,000 IU to about 90,000 IU, about 65,000 IU to about 85,000 IU, about 65,000 IU to about 80,000 IU, about 65,000 IU to about 75,000 IU, about 65,000 IU to about 70,000 IU, about 70,000 IU to about 120,000 IU, about 70,000 IU to about110,000 IU, about 70,000 IU to about 100,000 IU, about 70,000 IU to about 90,000 IU, about 70,000 IU to about 85,000 IU, about 70,000 IU to about 80,000 IU, about 70,000 IU to about 75,000 IU, about 75,000 IU to about 120,000 IU, about 75,000 IU to about 110,000 IU, about 75,000 IU to about 100,000 IU, about 75,000 IU to about 90,000 IU, about 75,000 IU to about 85,000 IU, about 75,000 IU to about 80,000 IU, about 80,000 IU to about 120,000 IU, about 80,000 IU to about 110,000 IU, about 80,000 IU to about 100,000 IU, about 80,000 IU to about 90,000 IU, about 80,000 IU to about 85,000 IU, about 85,000 IU to about 120,000 IU, about 85,000 IU to about 110,000 IU, about 85,000 IU to about 100,000 IU, about 85,000 IU to about 90,000 IU, about 90,000 IU to about 120,000 IU, about 90,000 IU to about 110,000 IU, about 90,000 IU to about 100,000 IU, about 100,000 IU to about 120,000 IU, about 110,000 IU to about 120,000 IU.

[0034] In some aspects, the methods described herein comprise administering the sacrosidase to a subject in need thereof, wherein the subject weighs <15 kg or less. In some aspects, the subject in need thereof weighs about 14 kg, about 13 kg, about 12 kg, about 11 kg, about 10 kg, about 9 kg, about 8 kg, about 7 kg, about 6 kg, about 5 kg, about 4 kg, about 3 kg, or about 2 kg. In some aspects, the methods described herein comprise administering a single dose of sacrosidase of about 5,000 IU to about 10,000 IU to a subject in need thereof that weighs <15 kg or less. In some aspects, the methods described herein comprise administering a single dose of sacrosidase of about 5,000 IU to about 10,000 IU to a subject in need thereof that weighs <15 kg or less with each meal and / or snack.

[0035] In some aspects, the methods described herein comprise administering the sacrosidase to a subject in need thereof, wherein the subject weighs >15 kg. In some aspects, the subject in need thereof weighs between 15 kg and about 150 kg, 15 kg and about 140 kg, 15 kg and about 130 kg, 15 kg and about 120 kg, 15 kg and about 110 kg, 15 kg and about 100 kg, 15 kg and about 90 kg, 15 kg and about 80 kg, 15 kg and about 75 kg, 15 kg and about 70 kg, 15 kg and about 60 kg, 15 kg and about 50 kg, 15 kg and about 40 kg, 15 kg and about 30 kg, about 20 kg and about 150 kg, about 20 kg and about 140 kg, about 20 kg and about 130 kg, about 20 kg and about 120 kg, about 20 kg and about 110 kg, about 20 kg and about 100 kg, about 20 kg and about 100 kg, about 20 kg and about 90 kg, about 20 kg and about 80 kg, about 20 kg and about 70 kg, about 20 kg and about 60 kg, about 20 kg and about 50 kg, about 20 kg and about 40 kg, about 20 kg and about 30 kg, about 30 kg and about 150 kg, about 30 kg and about 140 kg, about 30 kg and about130 kg, about 30 kg and about 120 kg, about 30 kg and about 110 kg, about 30 kg and about 100 kg, about 30 kg and about 90 kg, about 30 kg and about 80 kg, about 30 kg and about 60 kg, about 30 kg and about 50 kg, about 30 kg and about 40 kg, about 40 kg and about 150 kg, about 40 kg and about 140 kg, about 40 kg and about 130 kg, about 40 kg and about 120 kg, about 40 kg and about 110 kg, about 40 kg and about 100 kg, about 40 kg and about 90 kg, about 40 kg and about 80 kg, about 40 kg and about 50 kg, about 50 kg and about 150 kg, about 50 kg and about 140 kg, about 50 kg and about 130 kg, about 50 kg and about 120 kg, about 50 kg and about 110 kg, about 50 kg and about 100 kg, about 50 kg and about 100 kg, about 50 kg and about 90 kg, about 50 kg and about 80 kg, about 50 kg and about 70 kg, about 50 kg and about 60 kg, about 60 kg and about 150 kg, about 60 kg and about 140 kg, about 60 kg and about 130 kg, about 60 kg and about 120 kg, about 60 kg and about 110 kg, about 60 kg and about 100 kg, about 60 kg and about 90 kg, about 60 kg and about 80 kg, about 60 kg and about 70 kg, about 70 kg and about 150 kg, about 70 kg and about 140 kg, about 70 kg and about 130 kg, about 70 kg and about 120 kg, about 70 kg and about 110 kg, about 70 kg and about 100 kg, about 70 kg and about 100 kg, about 70 kg and about 90 kg, about 70 kg and about 80 kg, about 80 kg and about 150 kg, about 80 kg and about 140 kg, about 80 kg and about 130 kg, about 80 kg and about 120 kg, about 80 kg and about 110 kg, about 80 kg and about 100 kg, about 80 kg and about 90 kg, about 90 kg and about 150 kg, about 90 kg and about 140 kg, about 90 kg and about 130 kg, about 90 kg and about 120 kg, about 90 kg and about 110 kg, about 90 kg and about 100 kg, about 100 kg and about 150 kg, about 100 kg and about 140 kg, about 100 kg and about 130 kg, about 100 kg and about 120 kg, about 100 kg and about 110 kg, about 110 kg and about 150 kg, about 110 kg and about 140 kg, about 110 and about 130 kg, about 110 kg and about 120 kg, about 120 kg and about 150 kg, about 120 kg and about 140 kg, about 140 kg and about 130 kg, about 130 kg and about 150 kg, about 130 kg and about 140 kg, or about 140 kg and about 150 kg. In some aspects, the methods described herein comprise administering the sacrosidase to a subject in need thereof, wherein the subject weighs 15 kg, about 20 kg, about 25 kg, about 30 kg, about 35 kg, about 40 kg, about 45 kg, about 50 kg, about 55 kg, about 60 kg, about 65 kg, about 70 kg, about 75 kg, about 80 kg, about 85 kg, about 90 kg, about 95 kg, about 100 kg, about 105 kg, about 110 kg, about 115 kg, about 120 kg, about 125 kg, about 130 kg, about 135 kg, about 140 kg, about 145 kg, or about 150 kg. In some aspects, the methods described herein comprise administering a single dose of sacrosidaseof about 10,000 IU to about 50,000 IU to a subject in need thereof that weighs >15 kg. In some aspects, the methods described herein comprise administering a single dose of sacrosidase of about 17,000 IU or about 34,000 IU to a subject in need thereof that weighs >15 kg, In some aspects, the methods described herein comprise administering a single dose of sacrosidase of about 10,000 IU to about 50,000 IU to a subject in need thereof that weighs >15 kg with each meal and / or snack. In some aspects, the methods described herein comprise administering a single dose of sacrosidase of about 17,000 IU or about 34,000 IU to a subject in need thereof that weighs >15 kg with each meal and / or snack.

[0036] In some aspects, the methods disclosed herein comprise administering the sacrosidase to a subject in need thereof having a body mass index (BMI) of < 30 kg / m2. In certain aspects, the subject has a BMI of about 10 kg / m2to about 30 kg / m2, about 15 kg / m2to about 30 kg / m2, or about 25 kg / m2to about 30 kg / m2. In some aspects, the subject has a BMI or about 10 kg / m2, about 11 kg / m2, about 12 kg / m2, about 13 kg / m2, about 14 kg / m2, about 15 kg / m2, about 16 kg / m2, about 17 kg / m2, about 18 kg / m2, about 19 kg / m2, about 20 kg / m2, about 21 kg / m2, about 22 kg / m2, about 23 kg / m2, about 24 kg / m2, about 25 kg / m2, about 26 kg / m2, about 27 kg / m2, about 28 kg / m2, about 29 kg / m2, or about 30 kg / m2.

[0037] In some aspects, the methods described herein comprise administering the sacrosidase orally, intradermally, subcutaneously, intravenously, or by inhalation to the subject in need thereof. In some aspects, the sacrosidase is administered orally to the subject in need thereof. In some aspects, the sacrosidase is orally administered to the subject in need thereof as an oral solution. In some aspects, the oral solution administered to the subject in need thereof comprises sacrosidase and one or more pharmaceutically acceptable excipients. In some aspects, the pharmaceutically acceptable excipient in the oral solution comprising the sacrosidase is glycerol. In some aspects, the oral solution comprising the sacrosidase is a glycerol-water solution. In certain aspects, the oral solution comprising the sacrosidase is a 1 : 1 w / w solution.

[0038] In certain aspects, the oral solution comprises sacrosidase in a concentration of about 5,000 IU to about 11,000 IU per milliliter (mL). In some aspects, the oral solution comprises sacrosidase in a concentration of about 6,000 IU to about 10,000 IU or about 7,000 IU to about 9000 IU per mL. In some aspects, the oral solution comprises sacrosidase in a concentration of about 5,000 IU, about 5,500 IU, about 6,000 IU, about 6,500 IU, about 7,000 IU, about 7,500 IU, about 8,000 IU, about 8,500 IU, about 9,000 IU, about 9,500 IU,about 10,000 IU, about 10,500 IU, or about 11,000 IU per mL. In certain aspects, the oral solution comprises about 8,500 IU per mL.

[0039] In certain aspects, the methods described herein comprise administering about 50 pL to about 5 mL of the oral solution comprising the sacrosidase to the subject in need thereof at a single time. In some aspects, the methods described herein comprise administering about 100 pL to about 4.5 mL, about 500 pL to about 4 mL, about 750 pL to about 3.5 mL, about 1 mL to about 3 mL, about 1.5 mL to about 2.5 mL at a single time. In some aspects, the methods described herein comprise administering about 50 pL, about 75 pL, about 100 pL, about 125 pL, about 150 pL, about 175 pL, about 200 pL, about 225 pL, about 250 pL, about 257 pL, about 300 pL, about 325 pL, about 350 pL, about 375 pL, about 400 pL, about 425 pL, about 450 pL, about 475 pL, about 500 pL, about 525 pL, about 550 pL, about 575 pL, about 600 pL, about 625 pL, about 650 pL, about 675 pL, about 700 pL, about 725 pL, about 750 pL, about 775 pL, about 800 pL, about 825 pL, about 850 pL, about 875 pL, about 900 pL, about 925 pL, about 950 pL, about 975 pL, about 1 mL, about 1.25 mL, about 1.5 mL, about 1.75 mL, about 2 mL about 2.25 mL, about 2.50 mL, about 2.75 mL, about 3 mL, about 3.25 mL, about 3.5 mL, about 3.75 mL, about 4 mL, about 4.25 mL, about 4.5 mL, about 4.75 mL, or about 5 mL.

[0040] In certain aspects, the methods described herein comprise diluting the oral solution comprising the sacrosidase is diluted prior to administration to the subject in need thereof. In certain aspects, the oral solution comprising the sacrosidase is diluted in milk, water, or infant formula prior to administration to the subject in need thereof. In some aspects, the oral solution comprising the sacrosidase is diluted in milk, water, or infant formula to total amount of about 25 mL to about 200 mL prior to administration to the subject in need thereof. In some aspects, the oral solution comprising the sacrosidase is diluted in milk, water, or infant formula to a total amount of about 30 mL to about 175 mL, about 30 mL to about 150 mL, about 30 mL to about 125 mL, about 30 mL to about 100 mL, about 30 mL to about 75 mL, about 30 mL to about 50 mL, about 40 mL to about 150 mL, about 40 mL to about 125 mL, about 40 mL to about 100 mL, about 40 mL to about 75 mL, about 40 mL to about 50 mL, about 50 mL to about 175 mL about 50 mL to about 150 mL, about 50 mL to about 125 mL, about 50 mL to about 100 mL, 50 mL to about 75 mL, about 60 mL to about 175 mL, about 60 mL to about 150 mL, about 60 mL to about 125 mL, about 60 mL to about 100 mL, about 60 mL to about 75 mL, about 75 mL to about 175 mL, about75 mL to about 150 mL, to about 75 mL to about 125 mL, about 75 mL to about 100 mL, about 100 mL to about 150 mL, about 100 mL to about 125 mL, or about 125 mL to about 150 mL prior to administration to the subject in need thereof. In some aspects, the oral solution comprising the sacrosidase is diluted in milk, water, or infant formula to a total amount of about 25 mL, about 30 mL, about 35 mL, about 40 mL, about 45 mL, about 50 mL, about 55 mL, about 60 mL, about 65 mL, about 70 mL, about 75 mL, about 80 mL, about 85 mL, about 90 mL, about 95 mL, about 100 mL, about 105 mL, about 110 mL, about 115 mL, about 120 mL, about 125 mL, about 130 mL, about 135 mL, about 140 mL, about 145 mL, about 150 mL, about 155 mL, about 160 mL, about 165 mL, about 170 mL, about 175 mL, about 180 mL, about 185 mL, about 190 mL, about 195 mL, or about 200 mL prior to administration to the subject in need thereof.

[0041] In some aspects, the methods described herein comprises administering the sacrosidase with one or more additional active ingredients. In some aspects, the one or more additional active ingredient is an enzyme, a bile acid, a bile acid conjugate, or conjugates thereof. In some aspects, the one or more additional active ingredient is one or more enzymes selected from the group consisting of a sucrose, a lipase (e.g., a pancreatic lipase, gastric lipase), a protease, peptidase (e.g., carboxypeptidase, aminopeptidase, exopeptidase)), amylase, alpha-d-galactosidase, pancreatin, maltase, lactase, trypsin, pepsin, cellulase, chymotrypsin, papain, chitinase, carbohydrase, and bromelain. In some aspects, the one or more bile acids, bile acid conjugates, or conjugates thereof, is selected from the group consisting of cholic acid, chenodeoxycholic acid, and ursodeoxycholic acid.

[0042] In some aspects, the methods described herein results in one or more subjects exhibiting reduced incidence and severity of gastrointestinal symptoms after administrations of the sacrosidase as compared with the one or more subjects' symptoms without administration of the sacrosidase. In some aspects, the one or more of subjects administered sacrosidase exhibit a reduced incidence and severity of gastrointestinal symptoms as determined using a Total Symptom Score as compared with the gastrointestinal symptoms without administration of the sacrosidase.

[0043] In some aspects, the methods described herein achieve at least 50% reduction of constipation in at least 50% of patients with IBS-C after 4, 8, or 12 weeks of treatment compared to baseline (i.e., immediately prior to treatment). In some aspects, the methods described herein achieve at least 50% reduction of diarrhea in at least 50% of patients withIBS-D after 4, 8, or 12 weeks of treatment compared to baseline (i.e., immediately prior to treatment).

[0044] In some aspects, the methods described herein achieve a remission or cure rate of IBS of at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, or 99%. In some aspects, the methods described herein achieve a remission or cure rate of IBS of between about 10% to about 99%, about 10% to about 95%, about 10% to about 90%, about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 20%, about 20% to about 99%, about 20% to about 95%, about 20% to about 90%, about 20% to about 80%, about 20% to about 70%, about 20% to about 60%, about 20% to about 50%, about 20% to about 40%, about 20% to about 30%, about 30% to about 99%, about 30% to about 95%, about 30% to about 90%, about 30% to about 80%, about 30% to about 70%, about 30% to about 60%, about 30% to about 50%, about 30% to about 40%, about 40% to about 99%, about 40% to about 95%, about 40% to about 90%, about 40% to about 80%, about 40% to about 70%, about 40% to about 60%, about 40% to about 50%, about 50% to about 99%, about 50% to about 95%, about 50% to about 90%, about 50% to about 80%, about 50% to about 70%, about 50% to about 60%, about 60% to about 99%, about 60% to about 95%, about 60% to about 90%, about 60% to about 80%, about 60% to about 70%, about 70% to about 99%, about 70% to about 95%, about 70% to about 90%, about 70% to about 80%, about 80% to about 99%, about 80% to about 95%, about 80% to about 90%, about 90% to about 99%, about 90% to about 99%, or about 95% to about 99% as compared with baseline (i.e., immediately prior to treatment).

[0045] In some aspects, a subject of the methods described herein is assessed using the Subject's Global Assessment of Relief (“SGA”) as described in Muller-Lissner, et al., “Subject's global assessment of relief: an appropriate method to assess the impact of treatment on irritable bowel syndrome-related symptoms in clinical trials,” J. Clin. Epidemiology 56: 310-16 (2003) In some aspects, the subjects of the methods described herein achieve a reduction of IBS after 4, 8, or 12 weeks of treatment in at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% subjects in a population as evaluated by SGA as compared with baseline (i.e., immediately prior to treatment). In some aspects, the subjects of the methods described herein achieve a reduction of IBS after 4, 8, or 12 weeks of treatment between about 10 to about 99%, about 10% to about 95%, about 10% to about90%, about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 20% to about 99%, about 20% to about 95%, about 20% to about 90%, about 20% to about 80%, about 20% to about 70%, about 20% to about 60%, about 20% to about 50%, about 20% to about 40%, about 20% to about 30%, about 30% to about 99%, about 30% to about 95%, about 30% to about 90%, about 30% to about 80%, about 30% to about 70%, about 30% to about 60%, about 30% to about 50%, about 30% to about 40%, about 40% to about 99%, about 40% to about 95%, about 40% to about 90%, about 40% to about 80%, about 40% to about 70%, about 40% to about 60%, about 40% to about 50%, about 50% to about 99%, about 50% to about 95%, about 50% to about 95%, about 50% to about 90%, about 50% to about 80%, about 50% to about 70%, about 50% to about 60%, about 60% to about 99%, about 60% to about 95%, about 60% to about 90%, about 60% to about 80%, about 60% to about 70%, about 70% to about 99%, about 70% to about 95%, about 70% to about 90%, about 70% to about 80%, about 80% to about 99%, about 80% to about 95%, about 80% to about 90%, about 90% to about 99%, about 90% to about 99%, about 90% to about 95%, about 95% to about 99% of subjects in a population as compared to baseline (i.e., immediately prior to treatment).

[0046] In some aspects, the subjects to the methods described herein are assessed using the irritable bowel syndrome symptom severity scoring system (IBS SSS) as described in Francis, et aL “The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress.” Aliment Par macol Ther.. 11 :395-402 (1997). In some aspects, the methods described herein achieve at least 10% reduction in IBS SSS after 4, 8, or 12 weeks of treatment compared to baseline (i.e., immediately prior to treatment). In some aspects, the methods described herein achieve about 10% to about 99%, about 10% to about 90%, about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 20% to about 99%, about 20% to about 90%, about 20% to about 80%, about 20% to about 70%, about 20% to about 60%, about 20% to about 50%, about 20% to about 40%, about 20% to about 30%, about 30% to about 99%, about 30% to about 90%, about 30% to about 80%, about 30% to about 70%, about 30% to about 60%, about 30% to about 50%, about 30% to about 40%, about 40% to about 99%, about 40% to about 90%, about 40% to about 80%, about 40% to about 70% about 40% to about 60%,about 40% to about 50%, about 50% to about 99%, about 50% to about 90%, about 50% to about 80%, about 50% to about 70%, about 50% to about 60%, about 60% to about 99%, about 60% to about 90%, about 60% to about 80%, about 60% to about 70%, about 70% to about 99%, about 70% to about 90%, about 70% to about 80%, about 80% to about 99%, or about 80% to about 90% reduction of IBS SSS after 4, 8, or 12 weeks of treatment compared to baseline (i.e., immediately prior to treatment). In some aspects, the methods described herein achieve a reduction of IBS SSS after 4, 8, or 12 weeks of treatment compared to baseline (i.e., immediately prior to treatment) by more than 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11. In some aspects, the methods described herein achieve a reduction of IBS SSS after 4, 8, or 12 weeks of treatment compared to baseline (i.e., immediately prior to treatment) by more than 10, 20, 30, 40, 50, 60, 80, 90, or 100. In some aspects, the methods described herein achieve a reduction of IBS SSS after 4, 8, or 12 weeks of treatment compared to baseline (i.e., immediately prior to treatment) by more than 100, 200, 300, or 425. In some aspects, the methods described herein achieve a reduction of IBS SSS after 4, 8, or 12 weeks of treatment compared to baseline (i.e., immediately prior to treatment) by between about 70 to about 500. In some aspects, the methods described herein achieve a reduction of IBS SSS after 4, 8, or 12 weeks of treatment compared to baseline (e.g., immediately prior to treatment) by between about 70 to about 500 in at least 10%, 20%, 30%, 50%, 60%, 70%, 80%, or 90% subjects in a population.EXAMPLESEXAMPLE 1 : ANALYSIS OF SACROSIDASE ENZYMATIC ACTIVITY WITH SUCROSE AND FRUCTOOLIGOSACCHARIDE

[0047] The hydrolysis activity of sacrosidase solutions was tested by measuring their ability to hydrolyze solutions of sucrose and the FOS Orafti P95 (from BENEO-Orafiti S.A.). Various solutions of sacrosidase ranging in concentration from 1 lU / ml to 100 lU / ml were incubated for up to 180 minutes at 37°C or 50°C. The amount of hydrolysis was measured by adding a 0.10 ml of a solution containing NADP+, ATP and polyvinylpyrrolidone (PVP), and 0.02 ml of a solution containing enzymes hexokinase (HK) and glucose-6-phosphate dehydrogenase (G6P-DH) to a 2-ml sample of the sacrosidase solution. D-Glucose and D-fructose are phosphorylated by HK and adenosines’ -triphosphate (ATP) to glucose-6-phosphate (G-6-P) and fructose-6-phosphate (F-6-P)with the simultaneous formation of adenosine-5’ -diphosphate (ADP). In the presence of G6P-DH, G-6-P is oxidised by nicotinamide-adenine dinucleotide phosphate (NADP+) to gluconate-6-phosphate with the formation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH).

[0048] The amount of NADPH formed in this reaction is stoichiometric with the amount of D-glucose and measured by an increase in absorbance at 340 nm as compared to a blank. The absorbance was measured at 30, 60, 120, and 180 minutes after the addition of the sucrose or Orafti P95 to the sacrosidase solution. Experiments were also conducted to test the temperature dependency of the hydrolysis, with the hydrolysis of Orafti P95 samples being tested after incubation at 37 °C and 50 °C. The results of these experiments are summarized in Figures 1A-1E.

[0049] These results show that sacrosidase hydrolyzes al— P2 fructose-glucose bonds in sucrose and Orafti P95 in a time- and dose-dependent manner (see Figures 1A-1B). Sacrosidase also hydrolyzes (P2— >1) fructose-fructose glycosidic bonds in Orafti P95 in a time- and dose-dependent manner (see Figure 1C-1E). In all cases, sacrosidase showed significant hydrolysis activity, with total or near-total hydrolysis of glucosidic bonds observed in doses of 50 lU / ml or above after 60 min. The experiments on temperature dependency for the Orafti P95 also demonstrated that this reaction is temperaturedependent, with the sample incubated at 50 °C demonstrating increased hydrolysis as compared with the sample incubated at 37 °C (see Figure 1D-1E).EXAMPLE 2: CROSSOVER STUDY TO DETERMINE THE EFFECTIVENESS OF SACROSIDASE IN REDUCING THE INCIDENCE AND SEVERITY OF GASTROINTESTINAL SYMPTOMS IN SUBJECTS WITH FRUCTAN INTOLERANCE

[0050] A double-blind, placebo-controlled, crossover study will be conducted to determine if sacrosidase is effective in reducing the incidence and severity of gastrointestinal (“GT’) symptoms, including IBS, in subjects with fructan intolerance. A secondary objective is whether sacrosidase is effective in reducing the incidence and severity of abdominal bloating, and to assess the safety and tolerability of sacrosidase compared to placebo in subjects with fructan intolerance. Enrollment, selection criteria, study treatment, and product dosage information is summarized in Table 1.Table 1: Summary of Study Criteria

Claims

WHAT IS CLAIMED IS:

1. A method of treating a subject having irritable bowel syndrome (“IBS”) comprising administering sacrosidase to the subject in need thereof. A method of treating a subject having a form of carbohydrate maldigestion, comprising administering sacrosidase to the subject in need thereof.3 A method of treating a subject having fructan intolerance comprising administering sacrosidase to the subject in need thereof. The method of any one of claims 1-3, wherein the subject was previously diagnosed with non-celiac gluten sensitivity (NCGS).5 The method of any one of claims 1-4, wherein the sacrosidase is administered to the subject as a single dose of about 5,000 IU to about 50,000 IU.6 The method of claim 5, wherein the sacrosidase is administered to the subject as a single dose of about 8,500 IU.7 The method of claim 5, wherein the sacrosidase is administered to the subject as a single dose of about 17,000 IU.8 The method of claim 5, wherein the sacrosidase is administered to the subject as a single dose of about 35,000 IU.9 The method of any one of claims 1-8, wherein a single dose of sacrosidase is administered one or more times per day.10 The method of any one of claims 1-9, wherein a single dose of sacrosidase is administered with every meal.

11. The method of any one of claims 1-9, wherein a single dose of sacrosidase is administered with every snack.

12. The method of any one of claims 1-9, wherein a single dose of sacrosidase is administered with every meal or snack.

13. The method of any one of claims 1-9, wherein a single dose of the sacrosidase is administered with every meal and snack.

14. The method of any one of claims 1-13, wherein half of the single dose of the sacrosidase is administered before a meal or snack and the other half of the single dose of the sacrosidase is administered halfway through the meal or snack.

15. The method of any one of claims 1-13, wherein half of the single dose of the sacrosidase is administered before every meal and snack and the other half of the single dose of the sacrosidase is administered halfway through every meal and snack.

16. The method of any one of claims 1-13, wherein two-thirds of the single dose of sacrosidase is administered before a meal or snack and the other one-third of the single dose of the sacrosidase is administered halfway through the meal and snack.

17. The method of any one of claims 1-13, wherein two-thirds of the single dose of sacrosidase is administered before every meal and snack and the other one-third of the single dose of the sacrosidase is administered halfway through every meal and snack.

18. The method of any one of claims 1-13, wherein one-third of the single dose of sacrosidase is administered before a meal or snack and the other two-thirds of the single dose of the sacrosidase is administered halfway through the meal and snack.

19. The method of any one of claims 1-13, wherein one-third of the single dose of sacrosidase is administered before every meal and snack and the other two-thirds of the single dose of the sacrosidase is administered halfway through every meal and snack20. The method of any one of claims 1-19, wherein the subject weighs <15 kg.

21. The method of any one of claims 1-19, wherein the subject weighs >15 kg.

22. The method of any one of claims 1-19, wherein the subject has a body mass index(“BMI”) < 30 kg / m2.

23. The method of any one of claims 1-22, wherein the subject is administered a total daily dose of sacrosidase of about 5,000 IU to about 120,000 IU.

24. The method of any one of claims 1-23, wherein the sacrosidase is administered orally, intradermally, subcutaneously, intravenously, or by inhalation.

25. The method of claim 24, wherein the sacrosidase is administered orally.

26. The method of claim 25, wherein the sacrosidase is administered orally as an oral solution.

27. The method of claim 26, wherein the oral solution comprises glycerol.

28. The method of claim 27, wherein the oral solution comprises a 1 : 1 w / w glycerol-water solution.

29. The method of any one of claims 26-28, wherein the oral solution comprising sacrosidase is diluted with a liquid prior to administration to the subject in need thereof.

30. The method of claim 29, wherein the liquid is water, milk, or infant formula.

31. The method of claim 29 or 30, wherein the liquid is cold or room temperature.

32. The method of any one of claims 1-31, wherein the subject exhibits reduced incidence and severity of gastrointestinal symptoms after administrations of the sacrosidase as compared with the symptoms without administration of the sacrosidase.

33. The method of claim 32, wherein the reduced incidence and severity of gastrointestinal symptoms is based on the decreased incidence and severity of abdominal bloating experienced by the subject over a 24 hour period during a 7 day period in which the sacrosidase is administered.

34. The method of claim 32 or 33, wherein the reduced incidence and severity of gastrointestinal symptoms is determined using a Total Symptom Score.

35. The method of claim 32 or 33, wherein the reduced incidence and severity of gastrointestinal symptoms is determined using the Subject's Global Assessment of Relief (“SGA”).

36. The method of claim 32 or 33, wherein the reduced incidence and severity of gastrointestinal symptoms is determined using the irritable bowel syndrome symptom severity scoring system (IBS SSS).

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