Guest guest Posted February 25, 2007 Report Share Posted February 25, 2007 Hedgehog Small Molecule Agonist Neurological Disorders Programs Under Collaboration with Wyeth http://www.curis.com/pipeline_detail.php?id=4 The Hedgehog signaling pathway is essential for the formation of normal nerves and nerve networks in the central and peripheral nervous systems. Our scientists and academic collaborators have shown that treatment with a Hedgehog protein appears to accelerate the restoration of nerve function in models of nerve trauma and disease. This finding suggests that the Hedgehog pathway may have a potential therapeutic effect in treating certain human neurological disorders. Our scientists have developed a series of small molecule Hedgehog agonists that, in preclinical models, have shown to be capable of activating the Hedgehog pathway. Many of these small molecule Hedgehog agonists are orally available and can cross the blood brain barrier, a protective barrier formed by blood vessels and brain tissue that prevents most substances in the blood from entering the central nervous system. Small molecules that cross this blood brain barrier can potentially reach and treat the central nervous system, therefore making them attractive product development candidates for certain brain disorders. In 2004, our scientists presented a series of abstracts at the annual meeting of the Society for Neuroscience demonstrating positive preclinical results using the Hedgehog small molecule agonists in models of stroke, Parkinson's disease, and spinal cord injury. A third party has also reported on the use of a small molecule Hedgehog pathway agonist to promote the generation of new motor neurons in vitro. This motor neuron report was published in the Proceedings of the National Academy of Sciences U S A. 2004 May 4;101(18):7123-8. Motor neurons are nerve cells that are most typically found in the spinal cord, and their purpose is to establish functional connections with other tissues, usually muscles, to control movement and other functions. Damage to motor neurons can occur as result of injury, such as spinal cord injury, or as a result of disease, such as spinal muscular atrophy or amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease. We believe that the positive effects of the Hedgehog agonists in neuronal disease models are due to neuroprotection that is induced by activation of the Hedgehog signaling pathway. Neuroprotection is the prevention of the progressive death of cells in the brain caused by disease or injury. In addition, we believe that activation of the Hedgehog pathway results in an increased proliferation of stem cells in the brain. We are currently exploring the possibility that this may enable us to develop drugs that can promote the replacement of cells lost as a result of injury or disease. In January 2004, we entered into a collaboration agreement with Wyeth to continue the development of these drug candidates for the treatment of neurological disorders and other potential indications. Wyeth is one of the world's largest research-driven pharmaceutical companies with broad expertise in the development of drugs to treat neurological disorders and other diseases. Under the terms of the collaboration, Wyeth paid us an up-front license fee and is obligated to provide two years of research funding. In addition, if clinical development of any Hedgehog agonist technology-based products is successful, Wyeth is obligated to pay us clinical milestone payments and royalties on product sales. Wyeth has agreed to assume all future responsibility for clinical development of the Hedgehog small molecule and protein agonists as systemic treatments for neurological and other disorders. As part of the agreement, we have retained development and licensing options for certain therapeutic applications of Hedgehog agonist technologies, including topical applications for hair growth and local delivery applications for treatment of cardiovascular disease. Wyeth has a right of first negotiation to obtain an exclusive license to the cardiovascular applications of the Hedgehog agonist technology. If Wyeth declines its option, or if we are unable to reach an agreement with Wyeth on terms within the contractually specified period, we are free to seek another collaborator for this program. Recent Press Releases: Curis Announces Receipt of Extended Funding from Wyeth 11/21/2005 Report of Hedgehog Pathway Efficacy in Preclinical Model of Parkinson's Disease 12/17/2004 New Reports of Positive Preclinical Results using Small Molecule Hedgehog Agonists 10/25/2004 Hedgehog Signaling Promotes Blood Vessel Development and Restores Nerve Function 09/20/2004 Curis Issued U.S. Patent Covering Method for Treating Stroke 07/29/2004 Curis Collaboration with Wyeth Highlighted in Current Issue of BusinessWeek Magazine; Collaboration Seeks to Develop Treatments for Damaged Brain Tissues 05/18/2004 Curis Collaboration with Project A.L.S. Highlighted in Current Online Issue of Fortune Magazine 05/05/2004 Curis Issued U.S. Patent Covering Methods of Treating Motor Neuron Disorders such as Spinal Cord Injury and ALS 04/22/2004 Curis Issued U.S. Patent Covering Hedgehog Pathway Agonists 01/27/2004 Curis Announces Strategic Partnership with Wyeth Pharmaceuticals to Develop Therapeutics for Neurological Disorders 01/12/2004 Quote Link to comment Share on other sites More sharing options...
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