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发表于 2007-9-8 10:58
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下面的文章来自同一网站,但对该原理和展望说得更加详细一些:
Development Moves Forward for Hearing Loss Drug
September 7, 2007
FREMONT, Calif—Quark Pharmaceuticals Inc, a clinical-stage biopharmaceutical company focused on discovering and developing novel RNA interference-based therapeutics, announced today that it has expanded its relationship with the State University of New York at Buffalo, Center for Hearing & Deafness, which is the company’s primary site for the pre-clinical studies of its product candidate, AHLi-11, for the treatment of acute hearing loss. Quark initiated its collaboration with the State University of New York in 2005.
The current studies, led by Richard Salvi, PhD, focus on the in-depth analysis of the effect of AHLi-11 and other molecules in preventing chemotherapy-induced hearing loss. Based on these studies, Quark Pharmaceuticals expects to file an IND within 2007 for AHLi-11 for the prevention chemotherapy-induced hearing loss.
AHLi-11 is a siRNA-based drug that temporarily inhibits the expression of human gene p53. Cochlear hair cell apoptosis (cell death), a key factor in several of the more common causes of acute hearing loss, is believed to be induced by molecular mechanisms most likely associated with p53-dependent stress response. Inhibition of p53, therefore, is suggested as a potential modality for the prevention of ototoxic hearing loss, a common side-effect of certain drugs including aminoglycoside antibiotics and cancer therapeutics such as cisplatin, as well as acoustic trauma.
Quark has demonstrated delivery of siRNA into target cells in rats and monkeys along with its persistence in the cochlear hair cells for at least 15 days. In preclinical animal studies, AHLi-11 appears to protect cochlear hair cells from apoptotic cell death induced by the chemotherapeutic agents, cisplatin and carboplatin, and by acoustic trauma.
“We are encouraged by the advancement of AHLi-11 for acute hearing loss and look forward to filing an IND by year-end for the prevention of chemotherapy-induced hearing loss,” says Daniel Zurr, CEO of Quark Pharmaceuticals. “Up to a million people per year are treated with cisplatin in the United States and Europe, and the risk of serious hearing impairment is particularly devastating in children. With this in mind, Quark will continue its efforts to advance AHLi- 11 in response to this major unmet medical need.
“We are also thrilled to expand our relationship with Professor Salvi and his colleagues at the State University of New York,” added Zurr, “as it will enable us to deepen our understanding of the molecular processes underlying acute hearing loss and to examine several variables related to the impact of AHLi-11 as a curative measure. Our collaborations with leading academic institutions mark the ongoing development of our pipeline and reinforce Quark's expertise in the development of siRNA-based therapeutics that offer the potential to treat a wide range of disease targets.”
About AHLi-11
AHLi-11 is a synthetic siRNA that is a temporary and reversible suppressor of p53, and contains the same active compound as AKIi-5, Quark's drug candidate for the prevention of acute renal failure. AHLi-11 is in development for the prevention of acute hearing loss, initially induced by the ototoxic cancer therapeutic agent cisplatin. AHLi-11 is based on Quark’s proprietary, patented concept of temporary and reversible inhibition, for therapeutic purposes, of the expression of the transcription factor human p53, which is associated with DNA repair and apoptosis. In response to certain chemotherapeutic agents, such as cisplatin and carboplatin, molecular mechanisms, most likely associated with p53-dependent stress response, are suspected of triggering cochlear hair cell apoptosis. Temporary inhibition of p53 prevents apoptosis, allowing restoration of normal DNA and cellular integrity. The AHLi-11 active molecule was designed and patented by Quark. The Company has licenses for certain RNAi intellectual property from Alnylam and Silence Therapeutics. |
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发表于 2007-9-9 15:46
