Isis Pharmaceuticals, Inc has initiated a phase-1 study of Isis-SOD1Rx in patients with an inherited, aggressive form of Lou Gehrig's disease also known as familial amyotrophic lateral sclerosis (ALS). Approximately 20 per cent of all familial ALS cases are caused by a mutant form of superoxide dismutase, or SOD1. ISIS-SOD1Rx is an antisense drug designed to inhibit the production of SOD1. The ALS Association and the Muscular Dystrophy Association are providing funding for the development of Isis-SOD1Rx.

"There is a desperate need for new and more substantive treatments for ALS patients. The mission of the Northeast ALS Consortium is to help advance new therapeutic options for patients with ALS, and I am very pleased to be a co-chair on this important study evaluating Isis-SOD1Rx in people with familial ALS," said Merit Cudkowicz, co-chair of the Northeast ALS Consortium and a Professor of Neurology at the Massachusetts General Hospital of Harvard Medical School.

"It is evident that certain cases of familial ALS are related to mutant forms of SOD1. Therefore, the selective inhibition of SOD1 production could provide a way to improve the outcomes of these patients with ALS," said Timothy Miller, assistant professor of Neurology at Washington University School of Medicine and director of the Christopher Wells Hobler Laboratory for ALS Research at the Hope Center for Neurological Disorders. "This is the first study to administer an inhibitor of SOD1 directly into the central nervous system. Having been involved with Isis in the research and now the clinical development of ISIS-SOD1Rx, I am looking forward to co-chairing this study with Dr Cudkowicz and the Northeast ALS Consortium."

"Isis-SOD1Rx is our first antisense drug to enter clinical trials to treat a neurodegenerative disease and our first antisense drug to be administered directly into the central nervous system. Based on our earlier preclinical studies, we believe that Isis-SOD1Rx could offer an effective treatment for patients with familial ALS," said C Frank Bennett, senior vice president of Research at Isis Pharmaceuticals. "This study is the first step in demonstrating the applicability of antisense drugs to treat severe neurodegenerative diseases. We also continue to advance our earlier-stage programs toward human studies."

The phase-1 study of Isis-SOD1Rx is a placebo-controlled, dose-escalation study designed to assess the safety, tolerability and pharmacokinetic profile of Isis-SOD1Rx in patients with familial ALS that is caused by mutations within the SOD1 gene. The study consists of four cohorts with eight patients each. In this study, Isis-SOD1Rx will be administered intrathecally using an external pump to deliver the drug directly into the spinal fluid during a single, 12-hour infusion. The study will be conducted in multiple centers within the United States.

"This therapy will be the first treatment for ALS that is specifically aimed at the target, SOD1, known to cause ALS. The development of new treatments for ALS is an extremely challenging and costly process. The ALS Association has been pleased to co-fund this study and partner with Isis on this extremely promising treatment approach. It is only through the support of our generous donors that this type of advancement is made possible," commented Lucie Bruijn, chief scientist, The ALS Association.

"This is a watershed moment," said R Rodney Howell, chairman of the MDA Board of Directors. "More than 30 people with familial ALS caused by mutations in the SOD1 gene soon will receive infusions of a SOD1 inhibitor directly into their central nervous systems." Dr Howell added that "MDA has invested more than $270 million fighting ALS, and it's exciting to see an excellent dose-escalation study get underway to assess the safety of Isis-SOD1Rx."

ISIS-SOD1Rx is designed to inhibit the production of SOD1.

Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners.