August 31, 2006

Research Update — from ALSA’s National Office

The ALS Association Awards TREAT ALS Funding to Two Clinical Efforts Focused on Markers of Disease Progression

Roberta Friedman, Ph.D., ALSA Research Department Information Coordinator

[QUICK SUMMARY: Two clinical trials that emphasize new ways to track a patient’s progression and reliably reveal that a treatment is working are now funded through TREAT ALS, a new initiative of The ALS Association that promises real progress in finding ALS therapeutics.]

The ALS Association has awarded funds to two new proposals through its TREAT ALS initiative, Translational Research Advancing Therapy for ALS, a drug discovery program and clinical trials process that accelerates discovery and testing of clinical candidates for amyotrophic lateral sclerosis (ALS, also called Lou Gehrig’s disease).

The two grants fund early stage clinical trials that will test new methods to track progression of the disease as well as new treatment strategies in ALS patients. The trials have not yet begun to recruit participants.

Markers of disease progression that investigators have used in the past include muscle strength testing, survival time and the ALS Functional Rating Scale as well as measures of respiratory function. These methods demand relatively large numbers of patients and long times for follow up in clinical trials in order to see if a treatment is effective.

The new ways to look at the progress of the disease are brain imaging and a test of the electrical function of muscles that reflect their wasting in ALS. The new clinical trials will be testing these new methods to see if they can serve as surrogate markers of ALS progression that will more rapidly and reliably reveal that a treatment is working.

One trial will evaluate electrical impedance myography, a technique which measures the integrity and health of the muscle cells. This measure has the potential to serve as a marker of advancing disease in ALS. This painless, noninvasive electrical test does not depend on any effort on the part of the patient and could prove to be a reliable indicator that a new therapeutic is halting or slowing the progress of the disease.

The study investigators, Seward Rutkove, M.D., at Beth Israel Deaconess hospital in Boston, and Jeremy Shefner, M.D., Ph.D., of the State University of New York in Syracuse, will seek to confirm that this test of muscle function is a reliable index of the progress of ALS that would speed clinical testing of candidate therapies.

The other trial will see if a drug used in Alzheimer’s disease called memantine can help in ALS. In addition to traditional testing of ALS progression, magnetic resonance spectroscopy will be used confirm a difference in brain chemistry. Also, the investigators will use a measure of nerve response called motor unit number estimation to see if more spinal motor neurons survive in treated patients. Together, these methods should provide a comprehensive means to measure the response of the primary targets in ALS to treatment. The investigators in this trial, Sanjay Kalra, M.D., and K. Ming Chan, M.B., CH.B., of the University of Alberta, Canada, will also use established measures of disease progression that include the patient and caregiver questionnaire called the ALS Functional Rating Scale as well as muscle strength, respiratory and cognitive testing.

Memantine is already shown to be safe in people and has theoretical aspects that suggest it might have benefit in ALS. It acts on glutamate transmission, which is implicated in ALS. The only approved drug for ALS is riluzole which also affects glutamate messages in the nervous system. The investigators will test different doses of memantine in patients with ALS in order to plan for a large, Phase III trial of efficacy.

Magnetic resonance spectroscopy of the brain can show that a signal related to the integrity of neurons changes with progression of ALS. For more details, click here. The investigators will measure this signal at study enrollment and at intervals during the study to see if the signal changes reliably to reflect slowing of disease due to successful treatment effect.

Markers of the progress of ALS are vital to continued efforts to discover effective treatment for the disease, which remains a fatal diagnosis. Any new signposts that reliably show slowing of the disease will speed clinical testing of new candidate therapies, the key goal of the Association’s TREAT ALS initiative.