BioTech Company Reports RNAi Could be a Treatment for SOD1 ALS

August 2, 2004

The following is an update of the original story released on May 20, 2004.

The media continues to report a new technology that may lead to a treatment for patients with ALS who have the SOD1 mutation.  The technique is known as RNA interference (RNAi).  While the research using RNAi to reduce the levels of SOD1 mutant protein in ALS is exciting and encouraging, it is premature to predict what the effect and benefit for humans may be in the future.  In addition, there is no data yet showing that lowering of mutant protein SODI will reverse or slow the disease.  Furthermore, early diagnosis remains key.  When patients are diagnosed, usually 50% of their neurons are already lost in the region affected.  This therapy approach does not address this loss of neurons and, although further damage may be prevented, complete functional recovery may be impossible.  There are no animal data that provides evidence that the RNAi technology either slows or halts the disease process.

The SOD1 mutations cause ALS in 2% of all people with ALS, or 20% of all familial ALS. Results in cell culture were very encouraging, showing that RNAi was effective in destroying the mutant SOD1 and preventing cell death in a toxicity model that may be associated with this genetic mutation.

While the initial work with RNAi is very encouraging and hopeful as a future treatment for people with the SOD1 mutation, the technical challenge of how to deliver RNAi to lower the levels of mutant SOD1 in humans remains. Currently, experimental efforts are underway to use viral delivery (gene therapy) as a system to administer RNAi. The ALS Association is funding several laboratory studies to address this area, visit www.alsa.org/research/article.cfm?id=439 for more information.

A representative of the company developing the technology, CytRx, made a brief report on its RNAi work at an ALSA Advocacy Day workshop. The company plans to take all the necessary steps to initiate clinical trials in the near future.

More research is needed to develop a system that will deliver the RNAi compound to the proper locations and to further test animals; however, the technology is exciting and does offer realistic hope for patients with the SOD1 mutation. If successful, RNAi technology, which greatly reduces the genetic mutation, potentially could be effective with yet-to-be-discovered genetic mutations in ALS that, like the SOD1 mutation, cause toxicity.

For information about ALSA’s support of research with RNAi, visit

www.alsa.org/research/projects.cfm?

www.alsa.org/research/grant.cfm?id=167