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Medical Care

New approach to treating ALS

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a neurodegenerative disease that primarily kills motor neurons, leading to paralysis and death two to fiv years from diagnosis. Currently ALS has no cure. Despite promising early-stage research, the majority of drugs in development for ALS have failed. Now researchers at Thomas Jefferson University in Philadelphia have uncovered a possible explanation. In a study published November 20th 2014 in the “Annals of Clinical and Translational Neurology”, researchers show that the brain’s machinery for pumping out toxins is ratcheted up in ALS patients and that this machinery also pumps out medicine designed to treat ALS, thereby decreasing the therapeutic efficacy of the drug. The work showed that when these pumps are blocked, the drug becomes more effective at slowing the progression of the disease in mouse models.

A release from the university quotes co-senior author Piera Pasinelli, Ph.D., associate professor of neuroscience and Co-Director of the Weinberg Unit for ALS Research, as saying, “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.”

“Drug resistance via these types of cellular drug-pumps is not new,” says co-senior author Davide Trotti, Ph.D., associate professor of neuroscience and Co-Director of the Weinberg Unit for ALS research at Jefferson. “In fact, drug companies routinely check novel compounds for interactions with these transporter proteins, but they typically check in healthy animals or individuals.” Because of the investigators’ background in pharmacological sciences and ALS research, examining the role of drug transporter proteins made sense. But rather than look at healthy mice, the researcher looked at how these interactions changed in mouse models of the disease over time.

In research published earlier, the group showed that the function of the pumps changed as the disease progressed in mice, with the pumps becoming more active as the symptoms became more severe. “The ALS brain and spinal cord may be trying to compensate for the disease by generating more of these pumps,” says Dr. Trotti. But it was unclear whether this increase would really impact treatment.