Novel Pilot Clinical Trials For ALS Based on Disease Biomarkers

The ALS Association together with the ALS Finding a Cure Foundation recently announced a $3 million funding for two Phase II clinical trials via the ALS Accelerated Therapeutics (ALS ACT) initiative, a project focused on accelerating the discovery of new ALS therapies in part by funding pilot clinical trials based on biomarkers related to the disease. ALS biomarkers refer to distinctive parameters related to the disorder that can improve the diagnosis, assess disease progression and patients’ response to treatment.

ALS (amyotrophic lateral sclerosis) is a progressive neurodegenerative disease characterized by the gradual degeneration and atrophy of motor neurons in the brain and spinal cord that are responsible for controlling essential voluntary muscles, such as the ones related to movement, speaking, eating, and even breathing. ALS patients may become totally paralyzed and the majority dies due to respiratory failure within two to five years after diagnosis. It is estimated that more than 300,000 Americans suffer from the disease and there is currently no cure or life-prolonging treatments.

It has been suggested that inflammation contributes to ALS progression. One of the Phase II clinical trials funded is a placebo-controlled, six-month treatment study to assess the effects of NP001, a regulator of inflammation in the immune system, in ALS patients with high levels of two inflammatory markers – interleukin-18 (IL-18) and lipopolysaccharide (LPS). The trial will be led by Dr. Robert Miller from the California Pacific Medical Center in San Francisco in collaboration with the Northeast ALS Consortium (NEALS) and the Neuraltus Pharmaceuticals, Inc. With this trial, the research team expects to obtain further insight into ALS cases with overactive inflammation.

The other Phase II clinical trial funded is an eight-week study that will assess the effects of different doses of mexiletine on hyperexcitability markers. Mexiletine is a cardiac medication that is able to reduce the hyperexcitability of motor neurons, and may potentially protect them from toxic excitation. The trial will be led by Dr. Michael Weiss from the University of Washington Medical Center in Seattle in collaboration with NEALS. In case mexiletine can reduce neuron hyperexcitability, a larger trial will be conducted to assess its effects on neuron protection and disease progression.

“The use of biomarkers to accelerate the discovery of new therapies is a major focus of The ALS Association’s Strategic Plan,” said the Chief Scientist for The ALS Association Dr. Lucie Bruijn in a press release. “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.”