Principal Investigators:
Rodolfo Llinas, M.D., Ph.D., Bruce Cherksey, Ph.D., and Mutsuyuki Sugimori, Ph.D., M.D.
Department of Physiology and Neuroscience
New York University School of Medicine

During the past few years, it has become apparent that the traditional targets for therapeutic agents such as the alpha or dopaminergic receptors, may not be the most advantageous site for a drug to act. Calcium (Ca++) and potassium (K+) channels play a fundamental role in the function and metabolism of many cells and tissues. For example Ca++ channels regulate contraction of skeletal, cardiac and smooth muscle; they are essential in secretory processes, both in secretory cells and in neurotransmission. Ca++ channels, different from those found in other tissues, are fundamental for brain function. There are numerous K+ channels exhibiting varying responses to different blockers suggesting that selective stimulation and/or blocking may enable "fine tuning" for treating learning, memory and cardiovascular disorders.

Description of the Project:
Dr. Llinas and his coworkers have discovered two different types of neuronal channels, the T-type and the P-type channels, neither of which is acted on by organic, dihydropyridine calcium channel blockers. The T-type channel is a low- threshold Ca++ channel which is important in areas of the brain known as the inferior olive and thalamus. Blockers have been identified which block T-type channels with different affinities in various regions of the brain. The P-type channel which is blocked by a factor (FTX) in the venom of the funnel web spider, has been directly linked to synaptic transmission. The channel protein has been isolated, purified and its function reconstituted. The isolated protein can be used to screen for compounds with CNS activity (including analogues of FTX) which may be used in the treatment of memory disorders, particularly those associated with aging. Similar work is under way with the T-type channel which may be used as a target for novel psychotherapeutic agents for treating mental illness.

A series of compounds with K+ channel blocking activity have also been developed by Dr. Cherksey and verified using the lipid bilayer technique with vesicles fused from the brain, heart and kidney. Different K+ channel types display different sensitivities to the compounds with the large K+ channel (maxi channel) displaying the greatest sensitivity. Because Ca++ and K+ channels are diverse with multiple types present in a single cell, it has been difficult to characterize them due to overlap of function.

Applications:
NYU is seeking an industrial partner interested in developing and licensing new classes of Ca++ and K+ blockers active in the central nervous system as well as the kidney and heart.

These blockers have therapeutic potential as psychotherapeutic, cardiovascular, and neuromuscular agents.

Patent Status:
U.S. patent applications covering the channel proteins and compounds have issued.

For further information please contact:
New York University
Office of Industrial Liaison
650 First Avenue, New York, N.Y. 10016
Tel: (212)263-8178 Fax: (212)263-8189