Alnylam And Collaborators Publish New Pre-Clinical Research On Therapeutic Silencing Of Key Gene Implicated In Parkinson's Disease

Main Category: Parkinson's Disease
Also Included In: Genetics;  Neurology / Neuroscience
Article Date: 05 Nov 2008 - 8:00 PDT

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Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has published new research with collaborators at Mayo Clinic in the journal Molecular Neurodegeneration. The new pre-clinical findings demonstrate durable therapeutic silencing of the alpha-synuclein gene when small interfering RNAs (siRNAs), the molecules that mediate RNAi, are administered by direct delivery to the CNS in mice. Alpha-synuclein is believed to play a central role in the development of Parkinson's disease, where the accumulation of excess alpha-synuclein protein has been associated with the cause and/or pathway of the disease. There exists a significant need for disease modifying therapies for the treatment of Parkinson's disease, with an estimated 1.5 million Americans afflicted with the disease.

"These new data add to a growing body of knowledge on the applications of RNAi therapeutics for the treatment of neurodegenerative disorders," said David Bumcrot, Ph.D., Director, Research at Alnylam. "Experts believe that reducing the levels of alpha-synuclein in the brain may slow or even halt the progression of Parkinson's disease and its associated symptoms. To date, no drugs have been identified that are capable of lowering alpha-synuclein levels in the brain. New approaches like RNAi may pave the way for novel disease-modifying medicines for Parkinson's disease based on direct administration of siRNAs to the central nervous system of patients with this debilitating and incurable disease."

The published data (Lewis et al., Molecular Neurodegeneration 2008, 3:19 doi:10.1186/1750-1326-3-19) demonstrated that chemically modified siRNAs targeting alpha-synuclein resulted in significant and durable silencing of the gene in mice. An approximately 70% reduction in alpha-synuclein levels was observed in treated mice, as compared to controls. The results also showed that RNAi silencing of alpha-synuclein lasted for up to three weeks and that the effect was not limited to the immediate site of delivery. In these preliminary studies, the synuclein-specific siRNA was found to be well tolerated in the brain after direct CNS administration. These results suggest that RNAi therapeutics may eventually be useful in reducing the over expression of alpha-synuclein in patients with Parkinson's disease.

The study was conducted in collaboration with Mayo Clinic and funded by Mayo Foundation for Medical Education and Research and The Michael J. Fox Foundation (MJFF) under a 'Target Validation' grant awarded in 2005. Earlier this year, Alnylam was part of a research team awarded a new $3.8 million grant from MJFF to further develop an RNAi therapeutic for the treatment of Parkinson's disease. The four-year grant, which is part of the Foundation's LEAPS (Linked Efforts to Accelerate Parkinson's Solutions) initiative, was awarded to Alnylam, Mayo Clinic of Jacksonville, Florida, and the Parkinson's Institute and Clinical Center of Sunnyvale, California.

Alnylam has an agreement with Mayo Clinic whereby Mayo has granted Alnylam an exclusive license to certain patents and know-how. Mayo Clinic and inventors of this intellectual property may receive developmental milestone and/or royalty payments pursuant to this agreement.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia, and Huntington's disease. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, and Kyowa Hakko Kogyo. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam established "RNAi 2010" in January 2008 which includes the company's plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit http://www.alnylam.com.

Alnylam Forward-Looking Statement

Various statements in this release concerning Alnylam's future expectations, plans and prospects, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, as well as those risks more fully discussed in the "Risk Factors" section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.

Alnylam Pharmaceuticals