Method of Enhancing Neural Stem Cell Proliferation, Differentiation, and Survival Using Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)

Abstract

The present invention relates to a method of increasing the number and/or differentiation of neural stem cells and/or neural stem cell progeny using pituitary adenylate cyclase-activating polypeptide (PACAP). In a preferred embodiment, additional growth factors are also utilized. The present invention can be practiced in vivo and in vitro, rendering it useful for the treatment of neurodegenerative disease and other neural trauma.

Description

RELATED APPLICATIONS [0001] This application is a continuation application of U.S. application Ser. No. 10 / 630,967, filed Jul. 31, 2003, which claims the benefit of U.S. Provisional Application Ser. No. 60 / 399,390, filed Jul. 31, 2003. The entire disclosure of each of these priority applications is hereby incorporated by reference.FIELD OF THE INVENTION [0002] The present invention relates to a method of enhancing proliferation and differentiation of neural stem cells in vivo and in vitro using pituitary adenylate cyclase-activating peptide. In a preferred embodiment, additional growth factors are also utilized. The present invention has applications in the treatment of neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's Diseases. REFERENCES [0003] U.S. Pat. No. 5,128,242. [0004] U.S. Pat. No. 5,198,542. [0005] U.S. Pat. No. 5,208,320. [0006] U.S. Pat. No. 5,326,860. [0007] U.S. Pat. No. 5,521,069. [0008] U.S. Pat. No. 5,547,935. [0009] U.S. Pat. No. 5,623...

AI Technical Summary

Benefits of technology

[0066] Accordingly, a major object of the present invention is to provide both in vivo and in vitro techniques of enhancing neural stem cell proliferation and/or survival and/or differen

Problems solved by technology

While it was previously thought that cells of the adult mammalian central nervous system (CNS) have little or no ability to undergo mitosis and generate new neurons, recent studies have demonstrated that the mature nervous system does have some limited capability to produce new neurons.

This relative inability to produce new neural cells in most mammals (and especially primates) may be advantageous for long-term memory retention; however, it is a distinct disadvantage when the need to replace lost neuronal cells arises due to an injury or disease.

These diseases, which include Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis, have been linked to the degeneration of neuronal cells in particular locations of the CNS, leading to the inability of these cells or the brain region to carry out their intended function.

In addition to neurodegenerative diseases, brain injuries often result in the loss of neurons, the inappropriate functioning of the affected brain region, and subsequent behavior abnormalities.

This may be due to inappropriate firing of neurons, or the abnormal synthesis, release, and/or processing of neurotransmitters.

Demyelination of central and peripheral neurons occurs in a number of pathologies and leads to improper signal conduction within the nervous system.

Unfortunately, this type of treatment has been fraught with many complications including limited ability to transport drugs across the blood-brain b

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