January 6, 2020

“I Just Didn’t Understand”: On a Mission to Cure ALS

By Barbara J. Toman
Veronique Belzil, Ph.D.

For Veronique Belzil, Ph.D., the fight against amyotrophic lateral sclerosis (ALS) is personal. In 2000, while working as a psychologist in Canada, she watched her husband's uncle succumb to the disease. "The progression was so fast and his condition was so sad," she says. "I just didn't understand how this could happen."

That's a common experience for people who lose loved ones to ALS, a devastating neurodegenerative disease with no cure. But Dr. Belzil's next step was uncommon: Returning to school to pursue a doctorate in neuroscience, with a focus on ALS. "I decided to take this experience as a mission to find a treatment for this terrible disease," she says.

Now, as an epigenomics researcher for the Center for Individualized Medicine at Mayo Clinic's campus in Florida, Dr. Belzil is paving the way for improved diagnosis and treatment of ALS. "We've made tremendous progress in terms of understanding the biology behind the disease," she says. "There is great hope for these patients."

Often known as Lou Gehrig's disease, ALS affects nerve cells in the brain and spinal cord, causing loss of muscle control. About 5,000 people in the United States are diagnosed with ALS each year. Diagnosis occurs around age 60, and average survival is three years. Although ALS can be inherited ("familial ALS"), most people with ALS don't have a family history of the disease ("sporadic ALS").

"We've made tremendous progress in terms of understanding the biology behind the disease. There is great hope for these patients."

Veronique Belzil, Ph.D.

Finding treatments for ALS requires first understanding how the disease develops so researchers know what to target. About 30 genetic mutations have been identified as playing a role, including a mutation known as C9orf72, which was discovered at Mayo Clinic's campus in Florida. The most common mutation associated with ALS, the C9orf72 variation explains a large proportion of familial ALS and a small proportion of sporadic cases.

However, in more than 80% of people with ALS, the disease has no known genetic cause. What’s more, people with the same genetic mutation can have very different disease characteristics. "That indicates there must be something else that triggers the disease," Dr. Belzil says.

The answer may well lie in the epigenome — the factors such as environmental triggers and gene regulators that influence how a gene is expressed. Early in her research career, Dr. Belzil decided to investigate epigenetic changes in people with ALS.

"This was a new direction that wasn't being explored a lot at the time," she says. "The epigenome is very dynamic. But if we can understand these dynamics, then therapeutic strategies can be developed to target the regulators of these actions. The goal is to reverse the epigenetic changes that lead to neurodegeneration."

"The epigenome is very dynamic. But if we can understand these dynamics, then therapeutic strategies can be developed to target the regulators of these actions. The goal is to reverse the epigenetic changes that lead to neurodegeneration."

Dr. Belzil

Solving the ALS riddle will take time. But Dr. Belzil and her colleagues have already learned a lot. In one recent study, the researchers identified numerous occurrences of an epigenetic mechanism known as DNA methylation in people with ALS compared to people without the disease. That study was the first to find that methylation changes in familial and sporadic ALS are generally distinct, although people within each group shared thousands of these aberrations.

"Our results are particularly important for sporadic ALS cases, as there is currently no known common cause," Dr. Belzil says. "Aberrant methylation may be key to understanding the disease and developing treatments."

Other epigenetic changes under investigation include histone modifications and small RNA regulation. All of this work can potentially lead to the discovery of an ALS biomarker — a measurable indicator that the disease is present. Right now, ALS is difficult to diagnose early because it can mimic other neurological diseases.

"Clinically relevant biomarkers would facilitate early diagnosis of ALS and predict prognosis," Dr. Belzil says.

Biomarkers are also important for clinical trials of new treatments. "There is a lot of variation in how ALS manifests in patients," Dr. Belzil says. "A biomarker can group patients appropriately to determine if a new therapy is having an effect within that group."

Outside of the laboratory, Dr. Belzil is active in the ALS Association, a patient advocacy group. Her efforts include speaking to patients and caregivers about ALS as well as participating in sponsored walks and other fundraisers.

"Awareness of ALS has grown, and more researchers are working on it now," Dr. Belzil says. "It is a devastating disease not only for patients but also for caregivers and family members. Understanding ALS and developing therapies will have a major impact on all people affected by the disease."

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Tags: #Mayo Clinic Center for Individualized Medicine Epigenomics Program, ALS, amyotrophic lateral sclerosis, center for individualized medicine, Epigenomics, Lou Gehrig's disease, mayo clinic, neurodegenerative disorders, Precision Medicine, Research, Veronique Belzil

My brother David has been diagnosed with ALS for a little more than a year. He showed signs of it for close to three years and no Doctor was able to figure out what was wrong, until my sister whom he had been living with kept trying to bring him to each doctor —- finally found a doctor who recognised almost immediately that he had ALS. He has been taking medication that was made available to him only through a medical grant funding from those who have donated to the continuing research for a possible cure. He has slowed down in the progression, but without side effects. My hopes and prayers are that, you can also contact the Doctor for possible cure if you have ALS or any relative suffering for same disease here is their email healthcaremedicalcenter15@gmailcom

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COMMENT

My first symptoms of ALS occurred in 2011, but was diagnosed in 2013. I had severe symptoms ranging from shortness of breath, balance problems, couldn't walk without a walker or a power chair, i had difficulty swallowing and fatigue. I was given medications which helped but only for a short burst of time, then i decided to try alternative measures and began on ALS Formula treatment from Akanni herbal centre , It has made a tremendous difference for me (Visit www. akanniherbalcentre .com). I had improved walking balance, increased appetite, muscle strength, improved eyesight and others. 

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COMMENT
@clairegb

My brother David has been diagnosed with ALS for a little more than a year. He showed signs of it for close to three years and no Doctor was able to figure out what was wrong, until my sister whom he had been living with kept trying to bring him to each doctor —- finally found a doctor who recognised almost immediately that he had ALS. He has been taking medication that was made available to him only through a medical grant funding from those who have donated to the continuing research for a possible cure. He has slowed down in the progression, but without side effects. My hopes and prayers are that, you can also contact the Doctor for possible cure if you have ALS or any relative suffering for same disease here is their email healthcaremedicalcenter15@gmailcom

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