ALS ACT initiative to speed discovery of new ALS treatments

The ALS AssociationJul 1 2015

The ALS Association and the ALS Finding a Cure Foundation are pleased to announce $3 million in funding for two new Phase II clinical studies through the ALS Accelerated Therapeutics (ALS ACT) initiative. Created as a collaboration with the Northeast ALS Consortium (NEALS) and the ALS Finding a Cure Foundation, ALS ACT is devoted to speeding the discovery of new ALS treatments in part through funding pilot clinical trials that employ biomarkers.

ALS (amyotrophic lateral sclerosis) is a progressive neurodegenerative disease that affects neurons (nerve cells) in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. There is no cure and no life-prolonging treatments for the disease.

A biomarker is a measurement that can be used to improve diagnosis, classify disease subtype, track progression, ensure target engagement of the treatment, or determine response to therapy. Use of biomarkers allows trials to be shorter and smaller, speeding therapy development.

In collaboration with NEALS and Neuraltus Pharmaceuticals, Inc., Robert Miller, M.D. of the California Pacific Medical Center in San Francisco will lead a placebo-controlled, six-month treatment study to confirm a signal observed in a previous study of NP001, an immune system regulator. Inflammation is thought to be a contributing factor to ALS disease progression and existing NP001 data suggest that it may have an effect on inflammation in the immune system. Dr. Miller's study of NP001 will examine the response rate in individuals with ALS who have elevated levels of two inflammatory markers: interleukin-18 (IL-18) and lipopolysaccharide (LPS). The findings from this study are expected to inform the design of potential future studies for individuals whose ALS is characterized by overactive inflammation.

Also in collaboration with NEALS, Michael Weiss, M.D., of the University of Washington Medical Center in Seattle, will lead an eight-week study comparing the effect of several dosages of mexiletine on markers of hyperexcitability. A prior study showed that mexiletine was safe to use in ALS. Mexiletine is a cardiac medication that reduces hyperexcitability of motor neurons, which may help protect them from toxic excitation. The effect of mexiletine will be measured using transcranial magnetic stimulation, a non-invasive way to determine the degree of hyperexcitability in the brain's motor cortex, which controls movements. Demonstration that treatment can reduce hyperexcitability would provide a rationale for a larger trial to determine if this reduction helps protect the neurons and slow disease progress.

"The use of biomarkers to accelerate the discovery of new therapies is a major focus of The ALS Association's Strategic Plan," said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association. "The inflammatory markers in Dr. Miller's study, and the measurement of hyperexcitability in Dr. Weiss's study, will help us to better understand the role of these processes in ALS, and quickly show us whether targeting these processes can be effective therapeutically. It is gratifying to be able to partner with NEALS and the ALS Finding a Cure Foundation to support this vital work."