Last November, Dr. Piera Pasinelli, Ph.D., associate professor of neuroscience and Co-Director of the Weinberg Unit for ALS Research at Thomas Jefferson University, and her research team made an important discovery in the field of amyotrophic lateral sclerosis (ALS) research that may change the way the therapeutic protocols currently used to treat this debilitating disease are administered. They published their findings in an article, titled, “Inhibiting drug efflux transporters improves efficacy of ALS therapeutics” on November 20th in the Annals of Clinical and Translational Neurology.
ALS, also known as Lou Gehrig’s disease, is a progressive disease that attacks the nerve cells that control muscular moments such as walking and respiration. Patients diagnosed with the disease will have increasing problems with breathing, swallowing, and speaking or forming words. In the late stages of the disease, patients rely solely on caretaker assistance for all their needs, leading to significant effects on their psychological health. ALS is a terminal diagnosis in which most patients die from respiratory failure within 2 to 5 years. There are exceptions to this, such as the case with Dr. Stephen Hawking, who has lived with the disease for nearly 4 decades and whose remarkable life was the subject of the recent film “The Theory of Everything”
Presently, there are no curative treatment options available for ALS, and the ability to translate today’s research advancements achieved in animal models to efficacious treatment interventions in human patients has been limited. With the results published in this study, Dr. Pasinelli may possibly be changing that diagnostic landscape. Dr. Pasinelli and her team showed that the brain’s machinery for pumping out toxins is excessive in ALS patients and that this machinery also pumps out medicine designed to treat ALS. This pumping action decreases the therapeutic efficacy of the medications given. When blocking the pumping mechanism in mice, the drugs were found to be more successful in slowing the progression of the disease.
“This mechanism that normally protects the brain and the spinal cord from damage via environmental toxins, also treats the therapeutic drug as a threat and pumps that out as well. Blocking the pumps, or transporter proteins, improved how well the ALS drug worked in mice,” stated Dr. Pasinelli when explaining the results.
These crucial findings could be highly significant for the advancement of ALS research because the majority of drugs developed to treat the disease have failed.
“The research paves a way for improving the efficacy of an already ALS approved drug, if the findings hold true in human clinical trials,” says Dr. Pasinelli. “But more importantly it also sheds light on a basic pathological mechanism at play in ALS patients that might explain why so many treatments have failed, and suggests a way to re-examine these therapies together with selective pump-inhibitor.”
The results of this study could possibly change the clinical landscape of what is understood concerning the disease’s progression and how to enhance emerging and already-approved treatment options.