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New drug therapy could improve brain function and life expectancy of ALS patients

Ben-Gurion University of the Negev (BGU) researchers are developing a new therapy for Amyotrophic Lateral Sclerosis (ALS) using part of an existing FDA-approved drug that restores the central nervous system’s (CNS) immune defenses and increases life expectancy.

ALS, also known as Lou Gehrig’s disease, is a lethal, progressive neurodegenerative disorder that affects the motor nerve cells in both the brain and the spinal cord. The progressive degeneration of motor neurons leads to atrophy, paralysis and eventually death due to failure of the respiratory muscles.

Since the exact cause of ALS is unknown, current research has focused on extending the post-onset life expectancy, which is currently between two to five years for most patients.

Part of the disease’s progression is linked to increased activity of glial cells, a type of immune cell that damages and kills the body’s motor neuron cells and decreases their ability to cleanse the CNS environment.

Dr. Rachel Lichtenstein of the Avram and Stella Goldstein-Goren Department of Biotechnology Engineering at BGU has focused on reducing this negative immune response. “We found a way to thwart the glial cells from attacking and killing healthy brain cells,” says Dr. Lichtenstein.

She successfully redesigned a portion of MabThera, an FDA-approved drug used to treat certain autoimmune diseases and types of cancer, into a new molecule to treat ALS.

“Our experimental results on ALS transgenic mice showed a significant increase in life expectancy”, says Dr. Lichtenstein. “Since the drug is already approved, we believe that we will only need limited preclinical testing to reach the clinical phase earlier than other initiatives.”

“This could also have major implications on the life expectancy of other neurodegenerative disease patients with Alzheimer’s and Parkinson’s,” says Dr. Ora Horovitz, senior vice president of business development at BGN Technologies, BGU’s technology transfer and commercialization company. “Our new drug candidate may prove effective in boosting the self-cleansing mechanism of the human brain, thereby improving the lives of millions of people.” The researchers are now seeking a pharmaceutical company partner.

Currently, there are only two drugs available for ALS patients: Reluzole (Rilutek), which helps extend patient survival by only three to six months; and the recently FDA- approved Edaravone (Radicava), which has demonstrated relatively modest success.

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FDA approves drug to treat ALS

The U.S. Food and Drug Administration approved Radicava (edaravone) to treat patients with amyotrophic lateral sclerosis (ALS), commonly referred to as Lou Gehrig’s disease.

“After learning about the use of edaravone to treat ALS in Japan, we rapidly engaged with the drug developer about filing a marketing application in the United States,” said Eric Bastings, M.D., deputy director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “This is the first new treatment approved by the FDA for ALS in many years, and we are pleased that people with ALS will now have an additional option.”

ALS is a rare disease that attacks and kills the nerve cells that control voluntary muscles. Voluntary muscles produce movements such as chewing, walking, breathing and talking. The nerves lose the ability to activate specific muscles, which causes the muscles to become weak and leads to paralysis. ALS is progressive, meaning it gets worse over time. The Centers for Disease Control and Prevention estimates that approximately 12,000-15,000 Americans have ALS. Most people with ALS die from respiratory failure, usually within three to five years from when the symptoms first appear.

Radicava is an intravenous infusion given by a health care professional. It is administered with an initial treatment cycle of daily dosing for 14 days, followed by a 14-day drug-free period. Subsequent treatment cycles consist of dosing on 10 of 14 days, followed by 14 days drug-free.

The efficacy of edaravone for the treatment of ALS was demonstrated in a six-month clinical trial conducted in Japan. In the trial, 137 participants were randomized to receive edaravone or placebo. At Week 24, individuals receiving edaravone declined less on a clinical assessment of daily functioning compared to those receiving a placebo.

The most common adverse reactions reported by clinical trial participants receiving edaravone were bruising (contusion) and gait disturbance.

Radicava is also associated with serious risks that require immediate medical care, such as hives, swelling, or shortness of breath, and allergic reactions to sodium bisulfite, an ingredient in the drug. Sodium bisulfite may cause anaphylactic symptoms that can be life-threatening in people with sulfite sensitivity.

The FDA granted this drug orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted approval of Radicava to Mitsubishi Tanabe Pharma America, Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency is also responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.