Treatment for diabetes

Abstract

Methods and compositions for treating diabetes mellitus in a patient in need thereof are provided. The methods include administering to a patient a composition providing a gastrin / CCK receptor ligand, e.g., a gastrin, and / or an epidermal growth factor (EGF) receptor ligand, e.g., TGF-alpha, in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells. The composition can be administered systemically or expressed in situ by cells transgenically supplemented with one or both of a gastrin / CCK receptor ligand gene, e.g., a preprogastrin peptide precursor gene and an EGF receptor ligand gene, e.g., a TGF-alpha gene. The methods also include transplanting into a patient cultured pancreatic islets in which mature insulin-secreting beta cells are proliferated by exposure to a gastrin / CCK receptor ligand and an EGF receptor ligand.

Description

[0001] This application is a continuation-in-part of U.S. Ser. No. 09 / 127,028, filed Jul. 30, 1998, which is a continuation U.S. Ser. No. of 07 / 992,255, filed Dec. 14, 1992, which issued Mar. 23, 1999, as U.S. Pat. No. .sub.______, which disclosures are incorporated herein by reference.[0002] 1. Field of Invention[0003] This invention relates to a method for treating diabetes mellitus in an individual in need thereof by administering to the individual a composition comprising a gastrin / CCK receptor ligand and / or an EGF receptor ligand which effectively promotes differentiation of pancreatic islet precursor cells to mature insulin-secreting cells. The method is exemplified by administration of gastrin and transforming growth factor alpha (TGF-.alpha.) either alone or in combination to normal streptozotocin (STZ) induced diabetic and genetically predisposed diabetic Zucker rats.[0004] 2. Background[0005] Diabetes is one of the most common endocrine diseases across all age groups and p...

AI Technical Summary

Benefits of technology

[0022] The subject invention offers advantages over existing treatment regimens for diabetic patients. By providing a means to stimulate the adult pancreas to regenerate, not only is the need for traditional drug therapy (Type 2) or insulin therapy (Type 1 and Type 2) reduced or even eliminated, but the maintenance of normal blood glucose levels also may reduce some of the more debilitating complications of diabetes. Diabetic complications include those affecting the small blood vessels in the retina, kidney, and nerves, (microvascular complications), and those affecting the large blood vessels supplying the heart, brain, and lower limbs (mascrovascular complications). Diabetic microvascular complications are the leading cause of new blindness in people 20-74 years old, and account for 35% of all new cases of end-stage renal disease. Over 60% of diabetics are affected by neuropathy. Diabetes accounts for 50% of all non-traumatic amputations in the USA, primarily as a result of diabetic macrovascular disease, and diabetics have a death rate from coronary artery disease that is 2.5 times that of non-diabetics. Hyperglycemia is believed to initiate and accelerate progression of diabetic microvascular complications. Use of the various current treatment regimens cannot adequately control hyperglycemia and therefore does not prevent or decrease progression of diabetic complications.

Problems solved by technology

Use of the various current treatment regimens cannot adequately control hyperglycemia and therefore does not prevent or decrease progression of diabetic complications.

The clinical efficacy, i.e. whether treatment of the underlying effect is effective in changing the course of disease, can be more difficult to measure.

While the evaluation of the biological efficacy goes a long way as a surrogate endpoint for the clinical efficacy, it is not definitive.

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