Sirna Therapeutics expects to yield a clinical candidate for its Huntington's disease program before the end of the year after company researchers were able to achieve significant knockdown of the disease-causing gene resulting in improved motor function in a mouse model using a vector-expressed siRNA, according to CEO and President Howard Robin.
The update, which was presented at the Biotechnology Industry Organization's annual CEO and Investor conference in New York this week, represented one of the few times that Sirna has commented on the Huntington's disease program, which usually takes a back seat to the company's other pipeline programs.
"I'm going to spend a little time on Huntington's disease, which is something we haven't talked about recently but have been doing an awful lot of work on," Robin noted during his presentation, which also included an overview of the company's pipeline, intellectual property estate, and recent financial figures.
Huntington's disease is a member of a class of disorders known as polyglutamine diseases and is caused by the expansion of a CAG repeat in exon 1 of the gene huntingtin.
According to Robin, Sirna researchers have been able to achieve a 60-percent knockdown of huntingtin protein in a mouse model of the disease using an AAV vector-expressed siRNA targeting the gene. After this, "we wanted to make sure that not only could we knock down the [huntingtin] protein ... but see if we could actually improve motion and improve motor function in animals," he said.
Sirna expects "to select a clinical candidate in Huntington's disease by the end of this year."
To do so, Sirna scientists evaluated three groups of animals - two comprising Huntington's disease-model mice either treated or untreated with an siRNA and one comprising controls - on a so-called Rotarod system, which determines how long the animals can stay on a rotating rod in order to measure gait and motion. "The Huntington's disease mice had regained substantial motor function when treated with an siRNA targeting the huntingtin gene," Robin said.
With these data, Robin noted that Sirna expects "to select a clinical candidate in Huntington's disease by the end of this year." He did not provide a date for when an investigational new drug application for a Huntington's disease drug might be filed.
Sirna estimates the condition affects 30,000 people in the US, with about 200,000 more being pre-symptomatic. The company started working in the indication early on, hiring University of Iowa researcher Beverly Davidson as a full-time consultant in 2004 and licensing patents from the University of Iowa Research Foundation covering neurological disease targets using RNAi technology, including those relating to Huntington's disease, a few months later.
About a year ago, Sirna also inked a deal with Targeted Genetics to collaborate on an RNAi-based treatment for Huntington's disease. The deal gave Sirna the rights to use TGen's adeno-associated virus vector-based delivery technology (see RNAi News, 1/14/2005).
- Doug Macron ([email protected])