Propionic and / or butyric acid for use in the prophylactic and / or supportive therapeutic treatment of Parkinson's disease

Description

[0001] The invention relates to an agent for the prophylactic and / or supportive therapeutic treatment of Parkinson's disease.

[0002] Numerous diseases are associated with intestinal microbiome imbalance, meaning the intestinal microbiome is out of balance, either due to intestinal imbalance or the loss of components essential for maintaining bodily functions. Significant changes in the intestinal microbiome can be detected in these diseases, such as obesity, ulcerative colitis, multiple sclerosis (MS), Parkinson's disease, and presumably also psychoses, as well as in rheumatic diseases and psoriasis. This suggests that the microbiome and disease are intertwined, either through a common cause or through mutual influence.

[0003] It has also been shown that the gut microbiome can be influenced by the type of food consumed and is able to adapt to the requirements of the respective diet. This means that a gut flora that is unfavorable to a patient's immune status can be modified through dietary interventions, thereby improving the patient's immune status.

[0004] The invention is based on the finding that Parkinson's disease patients exhibit a characteristic alteration of the microbiome compared to healthy controls. In particular, bacteria that produce short-chain fatty acids are scarce or absent in the microbiome. Accordingly, there is a deficiency of short-chain fatty acids, which occur as degradation products in the intestine of a healthy control person. Braak postulated that Parkinson's disease begins in the intestine. This is consistent with the finding that transferring the microbiome from mice with Parkinson's disease to healthy mice produces a picture comparable to Parkinson's disease.

[0005] The deficiency of microorganisms producing short-chain fatty acids found in Parkinson's patients causes a deficiency, especially of acetic, propionic, and butyric acid. While acetic acid is supplied in abundance through the diet, the deficiencies in propionic and butyric acid are generally not compensated.

[0006] Alpha-synuclein, a transport protein found in the brain and involved in Parkinson's disease, can be detected in the intestines in very early stages of the disease and serves as an indicator of the disease. This also suggests a connection between the disease and what's happening in the intestines.

[0007] Attempts have been made to compensate for deficiencies in intestinal colonization through medication or dietary measures, but these have had only limited success.

[0008] M. Unger et al., Parkinsonism and Related Disorders 32 (2016), 66-72, discusses the abnormal abundance of intestinal bacteria and short-chain fatty acids in Parkinson's patients. Specifically, the protective effect of sodium butyrate on dopaminergic neurons is discussed using a Drosophila model.

[0009] S. Sharma et al., XP009544J83 (Sept. 2015) discusses the beneficial effect of sodium butyrate on motor deficits in Parkinson's disease rats induced with 6-hydroxydopamine and subsequently treated with apomorphine.

[0010] Surprisingly, propionic acid and butyric acid have been shown to have a positive effect on the development and progression of Parkinson's disease. This also applies to their physiologically acceptable salts and esters. It has also been found that the targeted administration of these substances improves the drug treatment of Parkinson's disease, thus having a potentiating effect. In particular, the dosage of dopaminergic medications commonly used to treat Parkinson's disease can be significantly reduced.

[0011] Accordingly, the invention relates to an agent for use in the prophylactic and / or supportive therapeutic treatment of Parkinson's disease, containing a physiologically effective amount of propionic acid and butyric acid and / or their physiologically acceptable salts or esters.

[0012] The agent according to the invention can be administered for both prophylactic and therapeutic purposes to individuals predisposed to Parkinson's disease or to Parkinson's patients. However, the agent is particularly suitable for the supportive therapeutic treatment of Parkinson's patients who are otherwise undergoing conventional drug treatment.

[0013] The agent according to the invention contains propionic acid and butyric acid, either alone or in combination. However, administration in the form of physiologically acceptable salts is preferred, with the emphasis on salts of physiologically important metals. These can include alkali and alkaline earth metal salts, as well as zinc and iron salts.

[0014] Particularly preferred are the sodium, potassium, magnesium and calcium salts of both propionic acid and butyric acid.

[0015] In addition, propionic and butyric acid can also be administered in the form of their esters. These include the esters of C1 to C6 alcohols, especially the methyl and ethyl esters. The esters are hydrolyzed in the body to form free acids.

[0016] The agent according to the invention can be administered in conventional forms, for example, in the form of tablets, coated tablets, pills, capsules, lozenges, powders, and granules. Administration in liquid form is also possible, such as juices, drops, and teas. In any case, the agent is intended for oral administration.

[0017] Preferred forms of administration are tablets, capsules, and powder. The tablets and capsules containing a unit dose of the agent according to the invention are preferably administered twice daily. The powder can, for example, be stirred into a drink or mixed with food.

[0018] A unit dose for the above-mentioned dosage forms is in the range of 0.2 to 5 g, in particular 0.3 to 3 g. A particularly preferred amount for tablets, capsules, and powder is 0.5 to 2.0 g, each intended for morning and evening administration, optionally also at midday, especially in conjunction with meals.

[0019] Particularly preferred is the combined administration of propionic and butyric acid or their salts and esters in a single dose, but also in separate form. The weight ratio can, for example, be in the range of 3:1 to 1:3, in particular 3:2 to 2:3, for the total doses specified above.

[0020] As already mentioned, the agent according to the invention can be used for the supportive therapeutic treatment of Parkinson's patients. In this case, it is administered in addition to the usual drug treatment, for example, together with levodopa and other dopaminergic medications as commonly used. The dosage of the agent according to the invention is as stated above.

[0021] The effects of butyric acid / butyrate have been investigated in patient studies involving more than 1,000 subjects, each lasting at least one year. A total of 6 g of butyric acid or butyrate (as salt) was administered together with the doctor's prescribed medication (levodopa, among others) in three daily doses, morning, noon, and evening, with meals. Significant improvements in general condition, particularly in motor function, were observed.

[0022] Surprisingly, the dopamine requirement of Parkinson's patients treated with butyric acid / butyrate was reduced by at least 50%, and in some cases by up to 90%. This is particularly significant because the medication commonly used for Parkinson's patients, not only levodopa, leads to some serious side effects, such as dizziness, nausea, tachyarrhythmia, psychosis, dyskinesia, and circulatory problems.

Claims

1. Agent for use in the prophylactic and / or supportive therapeutic treatment of Morbus Parkinson, containing a physiologically effective amount of propionic acid and butyric acid and / or physiologically acceptable salts or esters thereof.

2. Agent for use according to claim 1, characterized in that the salts of propionic acid and butyric acid are the alkali or alkaline earth salts.

3. Agent for use according to claim 2, characterized in that the salts are sodium salts, potassium salts, magnesium salts or calcium salts.

4. Agents for use according to any one of the preceding claims, characterized in that the esters are the methyl esters or ethyl esters.

5. Agent for use according to any one of the preceding claims in tablet form, capsule form or powder form.

6. Agent for use according to any one of the preceding claims, characterized in that it is assembled in individual doses of 0.2 to 5 g.

7. Agent for use according to claim 6, characterized in that a single dose contains 0.5 to 2.0 g of active ingredient, optionally together with conventional assembling agents and excipients.

8. Agent for use according to any one of the preceding claims, containing propionic acid and butyric acid or salts or esters thereof in a weight ratio of 25 / 75 to 75 / 25.