The ALS Association (ALSA) has funded three proposals through its new TREAT ALS initiative, Translational Research Advancing Therapy for ALS, a drug discovery program and clinical trials process that accelerates discovery and testing of potential therapies 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 reviewed and approved by the FDA before proceeding to enroll patients.

A third grant allows investigators to produce an important lab test to show whether a candidate treatment is affecting the targeted aspect of the disease process.

New Candidate Therapy

This pilot study will test a new therapeutic approach called antisense now being applied to ALS. ALSA funded the basic research that demonstrated the ability of antisense molecules to improve ALS symptoms in rats modeling the disease, noted Lucie Bruijn, Ph.D., ALSA science director and vice president. Following administration into the fluid filled spaces in the rats’ brains, antisense treatment was effective even when treatment began near the time of disease onset, a time most relevant to the majority of ALS patients who are diagnosed only after symptoms are apparent.

This initial trial in ALS patients will test safety and also establish the rate at which the antisense compound enters and is cleared from the body tissues after infusion by a tiny pump into the fluid surrounding the spinal cord. Safety data combined with the data on how the drug is handled by the body will guide design of a phase II/III treatment trial in patients with an inherited form of the disease that is due to a mutation in the gene for the protein, copper-zinc superoxide dismutase (SOD1).

The antisense pilot clinical trial will be guided by principle investigators Merit Cudkowicz, M.D., Massachusetts General Hospital in Boston and Richard Smith, M.D. of the Center for Neurologic Study in La Jolla, Calif. Timothy Miller, M.D., University of California, San Diego is a co-investigator with Dr. Smith and was instrumental in the preclinical work that has led to this trial. [For more background, please click here.]

Combination Therapies in Accelerated Clinical Testing

A second clinical trial funded by ALSA’s TREAT ALS initiative will compare two sets of combination therapies, each demonstrated to prolong survival in rodent models of the disease. Investigator Paul Gordon, M.D. at Columbia University in New York City will implement a new trial design to identify the superior treatment combination that merits further testing.

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. This streamlined clinical trial should serve as a model for future studies to speed decisions about clinical candidates for ALS.

The drugs celecoxib and minocycline will each be tested in combination with creatine in separate groups of ALS patients. If one or both combinations 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.

This selection study provides an excellent example of how TREAT ALS seeks to hasten the pace of clinical discovery in ALS, Bruijn said. [For more background on this study please click here.]

Crucial Lab Tool

The third project funded by TREAT ALS will provide a simple but as yet unavailable test to see if levels of a therapeutic target molecule are altered in ALS patients. This lab test to measure the target, called EAAT2 (excitatory amino acid transporter), can then be used during clinical trials. The test would determine if a drug actually changes the production of EAAT2 in individual patients and thus evaluates new drug candidates more definitively. [For further details on the proposed assay please click here.]