ENC Health Currents: Promising New Treatment For ALS

Jan 4, 2018


Approximately 15 people are diagnosed with ALS, or Lou Gehrig’s Disease every day in the United States. There is no cure, but a promising study from a Canadian research facility shows one medication used to treat a chronic and severe mental disorder may improve quality of life for those with ALS.  Jared Brumbaugh has more.

Amyotrophic Lateral Sclerosis is characterized by a gradual weakening of the muscles.  The disease causes the brain and spinal cord to stop transmitting signals to muscles, leading to atrophy. Most people with ALS die within three to five years due to respiratory failure.  It typically affects people between the ages of 40 and 70, however cases of the disease happen when people are in their 20s and 30s.

“I feel like even though ALS is becoming more widely known in our general population, it’s still quite rare.  So I always like to get our story out there.”

Rachel Williams is a Ph.D student at the ECU Medical Family Therapy Program.  Her uncle passed away in 2005 after a four year battle with ALS. He was 45.

“He was very, very active before his diagnosis. He loved playing sports, he loved to go running, coaching his children’s sports teams, he really just liked to be moving.”

Williams says her uncle started noticing early indicators of ALS such as numbness in his hands and problems with coordination.  After a serious fall which sent him to a hospital, Paul was diagnosed with Lou Gehrig’s disease in 2001.  

“You know I’m not sure I understood a lot of what was experienced in my family with this illness as it was happening, I was pretty small.  But I do remember just being absolutely heartbroken by it.”

Little is known about what causes ALS.  Some cases are genetic, but the majority are sporadic with no family history of the disease.  It occurs throughout the world with no racial, ethnic or socioeconomic boundaries.  It’s not known why, but according to the ALS Association of North Carolina, military veterans are approximately twice as likely to develop the disease.  Athletes also have a high incidence of developing ALS.

“It affects the motor neurons, the motor nerves in the brain and spinal cord and leads to progressive weakness particularly involving the limbs, but can also affect speech and breathing.”

Dr. Robert Frere is a neurologist and associate professor at the Brody School of Medicine.  He’s also the Medical Director of the Jim “Catfish” Hunter ALS Clinic in Greenville. 

“We’ve actually come a long ways over the past 20 years I would say in terms of our ability to treat this disorder and make the lives of individuals who have this condition better.” 

While the mechanism of what causes ALS is unknown, there are two treatments currently approved by the Food and Drug Administration that can slow the progression of the disorder.  Riluzole was shown to prolong the life of a person with ALS by at least a few months.  And most recently, Radicava was approved last year for the treatment of the disease. Now, Canadian researchers have found that a drug used to treat schizophrenia has the potential to slow the development of ALS and may even halt the progression of the disease.  Alex Parker is an Associate Professor in the Department of Neuroscience at the University of Montreal Hospital Research Centre.  

“We basically just did a blind screen.  We didn’t pick the drug, we sifted through about 4,000 molecules and in this group of molecules that we found, many of them were anti-psychotics and the one that worked the best was Pimozide.  So it was our animal models that told us what to do essentially.”

Over the past eight years, Parker and a team of researchers conducted experiments on worms, zebrafish, mice and a small sample of human subjects to study the effects of pimozide to stabilize the connections between the nervous system and the muscles.

“We were very, very surprised that of the 4,000 compounds, we had about 12, I think it was 12, that they were structurally or functionally related to anti-psychotics or neuroleptics and we thought there’s something strange going on here.”

Although ALS and schizophrenia are two very different diseases, Parker says research is showing there may be a genetic link between the two disorders.  People who have been treated for schizophrenia have a much lower incidence of ALS.  He says this may be because the drugs are being neuroprotective.  In addition, anti-psychotics like Pimozide are readily available and cheap, costing about 9 cents per pill.  But there are serious side effects that can occur when administered in high doses, such as mobility problems and tremors.

“The dose they were using in the first part of the clinical trial for ALS patients was too high because they were just using a dose that was prescribed for patients with schizophrenia.  You can’t use that for ALS patients because they’re much more fragile.”

The next step in the research process is a clinical trial in nine hospital across Canada involving 100 patients with ALS to determine the efficacy and safety of pimozide over a six month period.  Parker says they will study the effects of the drug administered at lower doses at a longer duration to conclude if pimozide preserves neuromuscular function or has a curative affect. 

“Pimozide may be effective in minimizing some of the ALS symptoms but longer term, now that we have this molecule, pimozide, we think we can design a new version in a couple of years where we can minimize the side effects completely and therefore you could use the active component from pimozide at higher doses and it might have a greater affect.  That’s more of the research angle, and that will be much longer.  But in the meantime, pimozide might be good enough for now.”

Findings from the study will be released in 2020.  Medical Director of the Jim “Catfish” Hunter ALS Clinic in Greenville Dr. Robert Frere says early positive results in trials doesn’t mean the drug will make it to the market as a treatment. 

“In fact, the odds are often against it. The same thing we’ve also found with animal models of ALS where we indeed might find something that seems to help in the animal models, but it doesn’t translate to the human condition.”

Dr. Frere adds over 25 compounds have been tested to treat ALS, but only two medications are approved.  Still, Rachel Williams who lost her uncle to ALS in 2005 says the idea of a new, more effective treatment gives her hope that one day there will be a cure for this debilitating disease.

“Slowing down the disease, that's promising in and of itself just to give a little bit more time for these individuals and their families, I think that's really hopeful.”

For more information on the study, go to: https://insight.jci.org/articles/view/97152