Research Breakthrough Identifies Common Cause Protein in ALS

ALS Researcher Teepu Siddique, MD

Researchers have discovered a common cause among the different forms of amyotrophic lateral sclerosis (ALS), known in North America as Lou Gehrig’s disease: a protein called ubiquilin2. For more than two decades, Dr. Teepu Siddique, professor of neurology at Northwestern University, and his research team have been searching for the cause and underlying mechanism of ALS, which leads to paralysis and eventually affects a patient’s ability to breathe or swallow on their own.

Dr. Siddique and his colleagues have discovered a common cause among the different forms of the neurodegenerative and eventually fatal disease – a protein, ubiquilin2, undergoes a critical mutation and fails to perform its task of recycling other damaged and malformed protein cells. Those unrecycled proteins accumulate and begin to interfere with vital nerve cells in the spinal cord and brain, which then no longer properly tell muscles what to do.

ALS Researcher Teepu Siddique, MD

This sort of protein degradation pathway is what contributes to ALS and possibly other degenerative disorders like Parkinson’s disease and even Alzheimer’s.  At the very least, such a discovery could lead to better strategies to treat these diseases.

It’s still not clear what may lead to ubiquilin2 malfunctioning. ALS occurs sporadically, hereditary in about just 1 in 10 individuals. Although ALS afflicts approximately 350,000 people of all racial and ethnic backgrounds worldwide, research into its cause has been difficult due to true study only being available at autopsy, when pathologists can test brain tissue for these protein issues.

The study’s co-author, Dr. Han-Xiang Deng noted, “Abnormality in protein degradation has been suspected, but there was little direct evidence before this study.”

The Northwestern University ALS Research Team

When a patient is alive, however, the signs and symptoms of a neurodegenerative disorder can sometimes look very similar to other motor-neuron disorders. In fact, one group of neurologists recently speculated that the face of ALS, baseball player Lou Gehrig, may not have actually died from amyotrophic lateral sclerosis, but perhaps instead from a traumatic head injury-related form of neurodegeneration termed chronic traumatic encephalomyopathy due to repeated concussions.

Right now only one drug has been approved for the treatment of ALS, and it offers just a slow-down of the disease’s progression. New treatments for ALS would be very welcome, and Dr. Siddique and his team are excited to have helped unlock the pathway there.

“This is the most hopeful I have been in 25 years of research,” said Dr. Siddique. “Previously, we were running in many different directions, but this is where we will focus from now on.”