| Alpha-7 Receptor Program
Stimulation of the vagus nerve, a nerve that links the brain with the major organs of the body, causes the release of a chemical neurotransmitter called acetylcholine. Acetylcholine has been shown to inhibit the release of cytokines that play a fundamental role in the inflammatory response, including TNF alpha. Research indicates that stimulation of the vagus nerve and the subsequent release of acetylcholine form the basis for a powerful anti-inflammatory feedback loop, the “Cholinergic Anti-Inflammatory Pathway” that the body uses to protect against excessive inflammation. Acetylcholine exerts anti-inflammatory activity by stimulating the nicotinic alpha-7 nicotinic acetylcholine receptor, or alpha-7 receptor, on cells involved in the inflammatory process.
Historically, a number of companies have focused on the alpha-7 receptor target for the treatment of central nervous system, or CNS, diseases. We believe the discovery of the role of this receptor in inflammation may lead to a new opportunity for the development of products to treat diseases in which inflammation plays a role. At Critical Therapeutics, we are working to develop anti-inflammatory products that harness the Cholinergic Anti-Inflammatory Pathway by stimulating the alpha-7 receptor on human inflammatory cells to treat serious inflammatory disease.
Therapeutic Opportunity
Our successful development of a product candidate targeting the alpha-7 receptor could lead to a novel treatment for severe acute inflammatory disease, as well as an oral anti-cytokine therapy that could be directed at chronic inflammatory diseases such as asthma, rheumatoid arthritis and Crohn’s disease. We believe the previous work on the alpha-7 receptor will assist the discovery of new, peripherally acting drugs that selectively stimulate the alpha-7 receptor. An alpha-7 receptor drug candidate taken orally could potentially have a strong market position against current injectable anti-TNF alpha biological therapies, particularly if it avoids the potential immunological response to therapy.
Development Strategy
With a small team of dedicated scientists, we are currently completing preclinical studies with compounds and knock-out mice that indicate a potential role for the alpha-7 mediated anti-inflammatory pathway in several clinically important inflammatory diseases. We have completed evaluations of proprietary small molecule product candidates in our alpha-7 program and have seen positive results with our molecules in animal models of allergic lung inflammation and acute lung injury. We have selected a first development compound that is currently in development and could enter into a human Phase I tolerability and proof-of-concept study in 2008. In addition, we are currently discussing possible partnering arrangements to help move this program forward as quickly as possible.
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