Epigenetics and the Promise of New ALS Treatments

The Ice Bucket Challenge raised awareness of ALS. Wikimedia Commons 

In the summer of 2014 the Ice Bucket Challenge went viral, raising awareness of amyotrophic lateral sclerosis, or ALS. ALS gradually kills motor neurons, taking away a patient’s ability to eat, speak, move, and breathe. It can also wear on neurons in the frontal lobe. Colloquially known as Lou Gehrig’s disease, ALS had previously entered the American consciousness in 1939 when the eponymous Yankees player was diagnosed. Despite public awareness and related donations to research, there is still no cure for the disease.
 
Professor Mariana Torrente (GC/Brooklyn College; Biology, Biochemistry, Chemistry/Chemistry) is at the forefront of research that could provide new inroads to ALS treatment. Torrente’s lab investigates the role of epigenetics — changes to gene expression that don’t modify the DNA code — in the disease. Because epigenetic mechanisms can be targeted with pharmaceuticals, this research could someday lead to new therapeutics.
 
One such mechanism is histone modification — changes to the protein “spools” around which DNA winds to form a compact package.
 
“When I started my independent career there were very few explorations into the histone modifications related to ALS,” Torrente says. “In fact, the first research paper out of my laboratory remains the only comprehensive characterization of histone modifications in ALS models.”
 
Torrente’s research weaves together her educational and research backgrounds, meshing epigenetics, molecular neurobiology, and protein folding. She had long been interested in subjects that combine chemistry and biology, she says, and following her Ph.D. work, decided to move towards a medically relevant field.
 
“When I moved on from my postdoctoral research, I asked if anyone had looked at ALS in this context, and the answer was no," Torrente says. Upon joining Brooklyn College, Torrente took on these investigations in her lab. Recently, two journals asked Torrente to write reviews on the subject, summing up what scientists today know about epigenetics’ function in the disease. One review appears in Translational Research, the other in BBA – Molecular Basis of Disease.
 
Epigenetic markers, such as histone modifications or DNA methylation, are like an extra layer of genetic instructions on top of DNA. Their research appeal lies in a special property.
 
“Epigenetic mechanisms are reversible,” Torrente says. “If there is an epigenetic problem, you can use a small molecule or peptide drug to counteract the effect and bring it back to normal.” This has already been done in research for cancer treatments, she notes. The two currently approved ALS drugs can extend a patient’s life but aren’t able to reverse the disease or stop its symptoms.
 
Torrente and her lab are continuing their study of histone modifications in ALS, now in both yeast models and human cell lines.
 
“The field is fairly young,” Torrente says. “It has gained prominence only in the last four or five years; people are starting to realize how important it is.”

Submitted on: APR 18, 2019

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