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Alnylam and Collaborators Publish New Pre-clinical Research on Therapeutic Silencing of Parkinsona?s Disease Gene

^{Published on 2010-08-23 05:55:27 - Market Wire}
 

CAMBRIDGE, Mass.--([ BUSINESS WIRE ])--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, and collaborators at The Parkinsona™s Institute and the Mayo Clinic have published new research findings in the journal Public Library of Science (PLoS). The new data show effective silencing of the alpha-synuclein gene with an RNAi therapeutic administered directly to the substantia nigra in the CNS of non-human primates. Alpha-synuclein is widely believed to play a central role in the development of Parkinsona™s disease, where the accumulation of excess alpha-synuclein protein in the substantia nigra has been associated with the cause and/or progression of the disease.

"These new findings add to a growing body of data on the applications of RNAi therapeutics for the treatment of neurodegenerative disorders, such as Parkinsona™s disease. Indeed, direct delivery of RNAi therapeutics in the CNS represents an important component of our overall product development strategy"

aThese new findings add to a growing body of data on the applications of RNAi therapeutics for the treatment of neurodegenerative disorders, such as Parkinsona™s disease. Indeed, direct delivery of RNAi therapeutics in the CNS represents an important component of our overall product development strategy,a said David Bumcrot, Ph.D., Director, Research at Alnylam. aWe remain committed to advancing this promising therapeutic modality to patients.a

Parkinsona™s disease is a chronic, degenerative neurological disorder that affects dopaminergic neurons in the brain involved in the control of movement. Symptoms include tremor, slowed movement, and rigid muscles. Recent research indicates that at least one million people in the United States, and more than five million worldwide, suffer from Parkinsona™s disease. There exists a significant need for disease modifying therapies for the treatment of Parkinsona™s disease as no such treatments are currently available.

aA wide range of genetic, epidemiologic, and laboratory data support the hypothesis that reducing levels of alpha-synuclein in the brain may slow or even halt the progression of Parkinsona™s disease and its associated symptoms,a said Donato A. Di Monte, M.D., Professor & Senior Research Group Leader at the German Center for Neurodegenerative Diseases (DZNE) in Bonn, and previously with The Parkinsona™s Institute. aAccordingly, we are encouraged by these important results, which for the first time demonstrate RNAi-mediated silencing of alpha-synuclein in the substantia nigra of non-human primates. To date, no drugs have been identified that are capable of lowering alpha-synuclein levels, and these data certainly support further development of an RNAi-based approach for the treatment of Parkinsona™s disease.a

The published data (McCormack et al., PloS ONE, 5: e12122, 2010) demonstrated that direct delivery of chemically modified siRNAs specific for alpha-synuclein resulted in significant silencing of the target gene in the substantia nigra in the non-human primate brain. A significant 40-50% suppression of both alpha-synuclein mRNA and protein levels was observed in treated animals, as compared to controls. In these preliminary studies, the siRNA was found to be well tolerated after direct CNS administration; no complications or adverse events were observed, including the absence of detectable microglial activation or change in the number of nigral dopaminergic neurons. These results suggest that RNAi therapeutics may be useful in reducing the pathogenic burden of alpha-synuclein in patients with Parkinsona™s disease.

The study was conducted in collaboration with scientists at Mayo Clinic and The Parkinsona™s Institute, and funded by a aLEAPSa (Linked Efforts to Accelerate Parkinsona™s Solutions) award from The Michael J. Fox Foundation for Parkinsona™s Research. Alnylam has an agreement with the Mayo Clinic whereby Mayo has granted Alnylam an exclusive license to certain patents and know-how related to alpha-synuclein.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as aa major scientific breakthrough that happens once every decade or so,a and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylama™s RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

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 worlda™s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics for the treatment of a wide range of disease areas, including respiratory syncytial virus (RSV), liver cancers, TTR-mediated amyloidosis (ATTR), hypercholesterolemia, and Huntingtona™s disease. In addition, Alnylam formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in manufacturing processes for biotherapeutic products, including recombinant proteins and monoclonal antibodies. The companya™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, Kyowa Hakko Kirin, and Cubist. Alnylam and Isis are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit [ www.alnylam.com ].

Alnylam Forward-Looking Statement

Various statements in this release concerning Alnylama™s future expectations, plans and prospects, including without limitation, its expectations regarding the development of effective and efficient approaches for RNAi therapeutics for the treatment of Parkinsona™s disease, 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, including Alnylama™s ability to discover and develop novel drug candidates, including RNAi therapeutics for the treatment of Parkinsona™s disease, as well as those risks more fully discussed in the aRisk Factorsa 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 Alnylama™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.