Alnylam and Collaborators Publish In Vivo Research on Validation of a Mammalian Host Gene Involved in Malaria Infection and on the Anti-Parasitic Efficacy of RNAi Therapeutics

Business Wire,  May 21, 2008  

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CAMBRIDGE, Mass. -- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced the publication of a new study in Cell Host & Microbe on the role of a host gene, heme oxygenase-1 (HO-1), in the cause and pathway of malaria parasitic infection. The collaboration was led by scientists at Unidade de Malaria in Portugal, and included scientists at Massachusetts Institute of Technology, Roche Kulmbach GmbH (formerly Alnylam Europe AG), and Alnylam. In the new research, in vivo studies demonstrated that HO-1 is a critical host factor involved in the liver stage of malaria infection in a mouse model. Results from the studies showed that RNAi therapeutics that silence HO-1 can significantly inhibit the initial liver stage of malaria infection and completely block the resulting transmission of disease to red blood cells.

"Our new research findings highlight the critical role of certain host-pathogen interactions occurring during malaria infection, in this case the role of HO-1," said Maria M. Mota, Ph.D., Associate Professor, Instituto de Medicina Molecular. "Our studies also point to the powerful approach of RNAi technology for in vivo validation of key disease-associated genes."

In the current study, HO-1 was validated as a host gene required for the liver stage of malaria (Plasmodium berghei and Plasmodium yoelii) infection. Liver HO-1 gene expression was significantly increased upon infection of mice with malaria sporozoites, the cells that infect new hosts. Mice lacking the HO-1 gene were found to be resistant to liver infection by malaria. Further, increased expression of HO-1 in transgenic mice was associated with an increased extent of malarial liver infection. RNAi technology using in vivo delivery of siRNAs, the molecules that mediate RNAi, provided validation of the HO-1 genetic data. RNAi treatment resulted in a greater than 60% silencing of HO-1 messenger RNA (mRNA) in the liver of treated mice. Mice treated with a HO-1 specific siRNA showed markedly reduced liver infection and complete attenuation of any detectable red blood cell stage infection, whereas animals treated with a control siRNA developed a normal course of infection. These data point to the potential therapeutic applications of RNAi for the treatment of a major parasitic infection such as malaria and to broader RNAi therapeutic strategies in infectious diseases through the targeting of host factors.

"We are thrilled to publish these new data for this serious global health problem, as RNAi technology and, potentially RNAi therapeutics, could lead to new treatment options," said Victor Kotelianski, M.D., Ph.D., Vice President of Research at Alnylam. "The World Health Organization estimates that each year 300 to 500 million cases of malaria occur and that more than 1 million people die of malaria, especially in developing countries. While the specific implications of RNAi therapeutics as a possible treatment for malaria remain to be fully understood, these new data certainly highlight the potential of RNAi in addressing major unmet medical needs."

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 "a major scientific breakthrough that happens once every decade or so," 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. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (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 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 hypercholesterolemia, liver cancers, 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, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established "RNAi 2010" 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 www.alnylam.com.