The ALS Association
1/16/2006 5:00:00 AM EST

The ALS Association (ALSA) has funded three proposals through its new TREAT ALS initiative, Translational Research Advancing Therapy for ALS, a program that accelerates discovery and testing of clinical candidates for amyotrophic lateral sclerosis (ALS, also called Lou Gehrig's disease).

Two of the grants fund early stage clinical trials that are testing new therapeutic strategies in ALS patients. These trials must now be approved by the FDA before proceeding to enroll patients. A third grant allows investigators to produce a test to show whether a candidate treatment is affecting the targeted aspect of the disease process.

One of the pilot studies will investigate safety of a cutting-edge technology called antisense, in one of the first applications of the strategy to a neurological disorder. Antisense treatment was effective in a rat model of ALS even when treatment began near the time of disease onset. Most ALS patients are diagnosed only after symptoms are apparent. The initial safety trial will also establish the rate the compound enters and is cleared from human tissues after infusion by a tiny pump into the fluid surrounding the spinal cord. The antisense drug is being supplied by Isis Pharmaceuticals, a leader in antisense therapeutics. Findings will guide design of a phase II/III treatment trial for familial ALS.

The second pilot trial will compare two sets of combination therapies, each demonstrated to prolong survival in rodent models of the disease. If neither combination turns out to provide beneficial effects in ALS, the study investigators will be able to decide this by enrolling just 120 patients. Celecoxib and minocycline will each be tested in combination with creatine, in separate groups of ALS patients. If one or both combination should produce a slower decline in function compared to a historic control group, further testing will proceed under an expanded, Phase III protocol with a placebo control.

The third project funded by TREAT ALS will provide a simple but as yet unavailable assay to see if levels of a therapeutic target molecule are altered in ALS patients. The test would determine if a drug actually changes the production of the target molecule, called EAAT2, in individual patients and thus evaluate new drug candidates more definitively.