Through the Pipeline

An ALS Therapy Development Institute Webcast summarizes research progress as of July 2009

by Quest Staff on July 27, 2009 - 5:00pm

On July 16, 2009, the MDA-supported ALS Therapy Development Institute (ALS TDI) gave its quarterly research update in a Webcast that's now archived on the Institute's site and accessible to all who register. (See Research Update Q209.)

Topics in the Webcast included the promising compound ALSTDI-00846; gene therapy; stem cells; barriers to drug development; and whether motor neurons are culprits or innocent bystanders in the ALS disease process.

MDA and the ALS TDI, in Cambridge, Mass., have collaborated to support research in amyotrophic lateral sclerosis (ALS) since 2007. That year, the Association, through its Augie's Quest initiative, pledged to give the Institute $18 million over three years.


Steve Perrin, CEO and chief scientific officer at the ALS TDI, said the compound ALSTDI-00846 has excited Institute researchers because of its effects on ALS mice. The compound modifies a specific immune-system response.

Perrin reported that ALS TDI scientists have studied more than 200 mice and found the new compound increased survival an average of 12 days. That may not sound like much, Perrin admitted, but he called it a "much bigger effect [in mice] than Rilutek," the only drug approved by the U.S. Food and Drug Administration (FDA) so far for the treatment of ALS.

Researchers at the MDA-supported ALS TDI are using a large-scale industrial approach to find biological changes associated with ALS that can be targeted for drug development.

In addition, body weight in the mice increased, and the loss of neurological function slowed.

More about ALS TDI-00846 can be found, along with many other topics, on the ALS TDI Forum.

Gene therapy

Gene therapy, Perrin said, is "coming back into the limelight" after being derailed some 10 years ago with the death of a patient with a metabolic disease who was participating in a gene therapy trial.

He noted that the ALS TDI is working with the biotech company Asklepios BioPharma of Chapel Hill, N.C., to develop gene therapies for ALS.

Stem cells

John McCarty, director of therapeutic investigations at the ALS TDI, reported on the International Society for Stem Cell Research conference he attended July 8-11 in Barcelona, Spain.

McCarty said stem cells have three basic applications in ALS: 1) as research tools; 2) as cell replacement therapies; and 3) as a vehicle for delivering therapeutic substances.

Not just about motor neurons

Another take-home message from the Webcast is that ALS is "not just about motor neurons," the cells in the brain and spinal cord that control muscle action and are lost in ALS. Other potentially important cell types that could be targeted to treat the disease may be glial cells, non-nerve cells in the nervous system; muscle fibers; and cells of the immune system, McCarty said.

Perrin echoed these sentiments, noting that "It can be difficult to get a drug into the central nervous system, so these other mechanisms open up therapeutic, drugable pathways." (Muscle fibers are outside the central nervous system, and immune-system cells have multiple locations.)

He went so far as to say that the motor neuron may in fact be an innocent bystander that becomes a victim in the ALS disease process.

Barriers to drug development

Perrin presented some of the barriers to drug development in ALS, citing "traditional pharmaceutical industry assumptions about ALS" that need to be challenged.

The industry has been averse to developing treatments for ALS, he said, because it believes 1) there are not a lot of patients, so the market is small; 2) the cause of ALS is unknown; and 3) there is no biological marker (biomarker) that can easily be measured to follow the course of the disease or the response to treatment.

Perrin stressed the importance of educating commercial firms that the market for ALS is potentially as large as it is for multiple sclerosis and is made smaller because ALS is such an aggressive disease. "If we could get a molecule that impacts the disease in ALS," he said, "the number of patients [living at any given time] is going to climb, as it did for MS."

He emphasized that research at the ALS TDI focuses on understanding the biological pathways involved in ALS and on defining biomarkers to follow the course of the disease and that progress is definitely being made.

Next Webinar in October

The next quarterly ALS TDI research Webcast will take place Oct. 5, 2009, during the Institute’s Leadership Summit.

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