Scientists are studying the effects of ALS gene mutations in mice and other animal models of the disease. And, they’ve been investigating treatments that might work against specific mutations.
One line of research has focused on gene therapy in mice with ALS genetic mutations. In gene therapy, researchers insert a new gene to replace a faulty one, or turn off — or silence — the flawed gene. In one study of mice, silencing the mutated SOD1 gene delayed amyotrophic lateral sclerosis symptoms by more than 100 percent, and prolonged the animals’ survival by nearly 80 percent of their normal lifespan.
The one challenge to using these models is that animals don’t always accurately represent how humans will respond to the same treatment. More gene therapy trials need to be conducted in people to determine whether the treatment is effective.
Genes can also help doctors predict whether standard treatments will work well for a particular person. For example, the drug lithium is thought to protect neurons, and possibly to improve survival in ALS. Some studies have found no evidence that lithium helps people with ALS live longer, but researchers say the key to the drug’s effectiveness is in targeting patients with the right genetic makeup. Researchers in the UK found that, among people with a variant in the UNC13A gene, taking lithium improved their odds of surviving 12 months from 40 percent to almost 70 percent. The same effect was not seen in people without the gene variant.
Another component to personalized medicine uses biomarkers — substances found in the blood or cerebrospinal fluid of people with ALS that can help predict the way their disease will behave. Testing for biomarkers could help researchers identify subgroups of patients who might gain the most benefit from certain medications. Biomarkers can also help monitor ALS progression, or predict a person’s outlook.
The path to personalized medicine
The challenge in developing personalized treatments for ALS is that more than 100 mutations in a few dozen different genes are responsible for the disease. Focusing in on the gene changes that are most likely to result in effective therapies has been challenging.
To promote progress in this field, in 2014 the ALS Therapy Development Institute — a research center in Cambridge, Mass. — introduced its Precision Medicine Program (PMP) — the first of its kind program for ALS. As of late 2017, the program had enrolled nearly 500 patients and had completed nearly 275 genome sequences. PMP’s goal is to partner patients with doctors to identify ALS subtypes, and develop new and more effective treatments for them.
March 16, 2020
Christopher Nystuen, MD, MBA