Alnylam has been a prominent player in the RNAi-as-therapeutics scene since it was founded last year: It has acquired the rights to high-profile intellectual property invented by company co-founder Tom Tuschl, closed a merger this summer with German peer Ribopharma, and established the first RNAi/big pharma drug development collaboration through a deal with Merck.
Despite all this, however, the company has for the most part been vague about which indications it is planning to tackle with its RNAi technology, citing metabolic or central nervous system disorders as examples rather than specific diseases. But this week, four of Alnylam’s research interests were disclosed, although only one through a formal announcement.
Alnylam issued a press release that it has formed a collaboration to develop RNA-based treatments for Parkinson’s disease with the Mayo Clinic. The partnership will focus on drugs that suppress the alpha synuclein gene, which researchers at the Mayo Clinic and NIH recently found to be overexpressed in people with the disease. Details of the findings were published in this week’s issue of Science (See Science, Oct. 31, 2003; 302: 5646, 841).
Under the deal, Alnylam will provide RNAi-based drug compounds that knock down alpha synuclein expression to the Mayo Clinic for testing in in vitro and in vivo experiments. The company will also provide the Mayo Clinic with research funding, as well as milestones and royalties on future product sales. Alnylam will retain the full rights to all compounds resulting from the effort.
Alnylam president and CEO John Maraganore told RNAi News the company is also in discussions with medical device companies as it plans for clinical testing of Parkinson’s disease drug candidates. “We’re not expecting siRNAs to go through the blood-brain barrier,” he said. “We’re expecting to work closely with device manufacturers to basically have a local delivery of the siRNA to the CNS.”
In terms of Alnylam’s other areas of interest, Maraganore said that while the alpha synuclein announcement “might be the first time we’ve talked about a specific molecular target, this is not the only program in the company.” He added that the company is looking at other targets such as apolipoprotein B (ApoB) for hyperlipidemia and protein-tyrosine phosphatase 1B (PTP1B) for diabetes.
Maraganore also confirmed that the company is working with researchers at Rockefeller University on hepatitis C.
At the New York Academy of Sciences’ first RNAi symposium this week, Rockefeller University researcher Glenn Randall noted that Alnylam has taken an interest in the hepatitis C work he and his colleagues have been conducting in the lab of Charles Rice, and told RNAi News that a relationship between the two has existed for some time.
Randall said that he and his colleagues began looking at applying siRNAs against hepatitis C shortly after Tuschl et al. published a paper in Nature two years ago describing how 21-nucleotide siRNA duplexes suppress gene expression in mammalian cells.
Randall’s work, detailed in the Proceedings of the National Academy of Sciences early this year, showed that while hepatitis C does not appear to trigger the RNAi process, siRNAs can be designed to silence both cellular lamin A/C and hepatitis C virus RNAs in Huh-7 hepatoma cell lines, which support replication of the virus (See PNAS, Jan. 7, 2003; 100: 1, 235-240).
“It appears that the virus isn’t naturally activating RNAi,” Randall said, but “we do see extremely efficient clearance of the virus if we induce RNAi by introducing small interfering RNAs. Basically, you get a clearance of viral RNA antigen expression from about 98 percent of the cells. It was a nice example of non-cytolytic clearance.”
This work, Randall said, piqued the interest of Alnylam, and early this summer Rockefeller and the company signed material transfer agreements, which Maraganore said involve the company providing the Rice lab with proprietary siRNAs for testing, but not with funding.
“We’re working with Alnylam and trying to find good targets for therapies and delivery systems, identifying optimal siRNAs, as far as ones that should be highly conserved and delivery methods which would be useful in vivo,” Randall added.