Title:  Methods for treating diabetes

United States Patent:  6,337,075

Assignee:  Allergan Sales, Inc. (Irvine, CA)

Filed:  January 26, 2000

The invention encompasses a method for treating hyperinsulinemic type 2 diabetes by local administration of a neurotoxin, such as a botulinum toxin, into the pancreas, thereby reducing insulin secretion from a B cell, and a method for treating hypoinsulinemic type 2 diabetes by local administration of a neurotoxin, such as a botulinum toxin, into a sympathetic ganglion, thereby reducing an inhibitory effect upon insulin secretion.

SUMMARY OF THE INVENTION

The present invention meets this need and provides an effective, non-surgical resection, relatively long term, non-radiotherapy, non-systemic drug administration, therapeutic method for treating type 2 diabetes.

A method for treating diabetes according to the present invention can be carried out by local administration of a neurotoxin to a pancreas. The neurotoxin can be administered in an amount of between about 10^-3 U/kg and about 35 U/kg. Preferably, the neurotoxin is administered in an amount of between about 10^-2 U/kg and about 25 U/kg. More preferably, the neurotoxin is administered in an amount of between about 10^-1 U/kg and about 15 U/kg. Most preferably, the neurotoxin is administered in an amount of between about 1 U/kg and about 10 U/kg. In many instances, an administration of from about 1 units to about 500 units of a neurotoxin, such as a botulinum toxin type A, provides effective and long lasting therapeutic relief. More preferably, from about 5 units to about 200 units of a neurotoxin, such as a botulinum toxin type A, can be used and most preferably, from about 10 units to about 100 units of a neurotoxin, such as a botulinum toxin type A, can be locally administered into a target tissue such as the pancreas or a sympathetic ganglion with efficacious results.

The neurotoxin can be made by a Clostridial bacterium, such as by a Clostridium botulinum, Clostridium butyricum, or Clostridium beratti bacterium. Additionally, the neurotoxin can be a modified neurotoxin, that is a neurotoxin that has at least one of its amino acids deleted, modified or replaced, as compared to the native or wild type neurotoxin. Furthermore, the neurotoxin can be a recombinant produced neurotoxin or a derivative or fragment thereof.

A method according to the present invention can be used to treat type 2 diabetes, such as (early) phase 1, middle or late phase type 2 diabetes. Notably, the neurotoxin, when injected into the pancreas, can act to reduce an insulin secretion and to reduce a glucagon secretion from the pancreas.

The neurotoxin can be a botulinum toxin, such as one of the botulinum toxin serotypes A, B, C₁, D, E, F or G. Preferably, the neurotoxin is botulinum toxin type A and the neurotoxin is locally administered by direct injection of the neurotoxin into the pancreas (when hyperinsulinemic diabetes is to be treated).

A further method within the scope of the present invention can also comprise administration of an agent for reducing insulin resistance prior to or concurrent with the local administration of the neurotoxin to the pancreas.

A detailed embodiment of a method within the scope of the present invention for treating type 2 diabetes can comprise the step of injecting a therapeutically effective amount of a botulinum toxin into a pancreas of a human patient, thereby reducing an insulin secretion from an islet B cell and treating type 2 diabetes. In this method, the type 2 diabetes is accompanied by hyperinsulinism and the insulin secretion is a cholinergic influenced insulin secretion.

Another detailed embodiment of a method within the scope of the present invention for treating type 2 diabetes of a human patient can comprise the step of local administration to a cholinergic influenced islet B cell containing, pancreatic tissue of a human patient of a therapeutically effective amount of botulinum toxin type A, thereby reducing a cholinergic influenced excessive insulin secretion from the pancreatic islet B cell and treating the type 2 diabetes.

Another method within the scope of the present invention is a method for treating excessive glucagon secretion by injecting a therapeutically effective amount of a botulinum toxin into a pancreas of a human patient, thereby reducing a glucagon secretion from an islet A cell.

A method for treating phase 2 NIDDM according to the present invention can be by injecting a therapeutically effective amount of a botulinum toxin into a pancreas of a human patient.

Another method within the scope of the present invention is a method for treating type 2 diabetes by administration of a neurotoxin to a sympathetic nervous system of a patient. In this method the neurotoxin is locally administered to a sympathetic ganglion which innervates a B cell and the type 2 diabetes is accompanied by hypoinsulinism.

A detailed embodiment of a method within the scope of the present invention for treating type 2 diabetes of a human patient can comprise the step of in vivo, local administration to a sympathetic ganglion, which innervates a pancreatic islet B cell of a patient, of a therapeutically effective amount of a botulinum toxin, thereby increasing a deficient insulin secretion from a pancreatic tissue and treating the type 2 diabetes.

The present invention therefore includes within its scope a method for treating the most prevalent form of diabetes (type 2 or NIDDM) by local administration of a neurotoxin to a pancreas or to a sympathetic ganglion thereby treating the diabetes.

A detailed embodiment of the present invention is a method for treating diabetes by injecting a therapeutically effective amount of a botulinum toxin into a pancreas of a human patient, thereby reducing a secretion from a pancreatic cell and treating the diabetes. The secretion treated can be an insulin secretion and the pancreatic disorder can be a NIDDM. Preferably, the secretion treated is a cholinergic influenced secretion and the botulinum toxin used is botulinum toxin type A, although the botulinum toxin can selected from the group consisting of botulinum toxin types A, B, C (i.e. C₁), D, E, F and G.

As used herein "local administration" means direct injection of the neurotoxin into the pancreas or into a sympathetic ganglion. Systemic routes of administration, such as oral and intravenous routes of administration, are excluded from the scope of the present invention.

Claim 1 of 30 Claims

I claim:

1. A method for treating diabetes, the method comprising the step of local administration of a botulinum toxin to a cholinergicly innervated pancreatic cell, thereby reducing an insulin secretion from the cholinergicly innervated pancreatic cell.

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