Novel Therapeutic Approach Using Protein Supplementation Could Delay ALS Symptoms

Supplementation of the protein in the nerve cells prevented nerve degeneration, muscle atrophy, and paralysis in an amyloid lateral sclerosis mouse model.

New research has found that a single protein that exists in the spinal cord could help delay symptom onset of amyloid lateral sclerosis (ALS), potentially alleviating ALS-related muscular atrophy and paralysis.

The protein, called mitofusion 2 (Mfn2), often becomes depleted during ALS, leading investigators to question whether increasing supplementation of this protein in the spinal cord could be a novel therapeutic approach.

The research was led by Xinglong Wang, PhD, associate professor of pathology at Case Western Reserve School of Medicine.

In the study, which was published in Cell Metabolism, the researchers tested the most widely used ALS mouse model. They genetically engineered the mice to have increased levels of Mfn2, but only in nerve cells that extend from the spinal cord and connect to muscle fibers.

According to the researchers, mice with high Mfn2 levels in these nerves were a healthy weight and did not experience the muscle atrophy, gait abnormalities, or reduced grip strength that mice with ALS in the control groups developed. Additionally, mice that underwent heavy sciatic nerve damage also benefited from increased Mfn2 levels, the study authors noted.

The researchers indicated that supplementing the protein specifically in nerve cells is sufficient to prevent skeletal muscle loss in ALS and aged mice.

Related Covereage: Link Confirmed Between Protein Mutation and ALS

According to their findings, Mfn2 coexists with nutrients in mitochondria and the mitochondria works to transport the nutrients along the nerve cell extensions to the point where nerve cells and muscle fibers meet. “This is a novel, previously unrecognized role for mitochondria,” the researchers wrote.

The nutrient, calpstatin, inhibits harmful enzymes that break down nerve and muscle fibers. As a result, the nutrient helps prevent enzymes from destroying synapse connections, preventing degeneration and muscle atrophy. According to the researchers, using the method allowed them to delay ALS symptom onset by 67 days.

“Mfn2 deficiency or mutations are commonly observed in patients with ALS, peripheral neuropathy, Alzheimers disease, and other neurodegenerative diseases in which synaptic loss has long been recognized as a prominent early feature,” Dr Wang said in a press release. “Supplementing Mfn2 may be a common and effective therapeutic approach to treat a wide range of diseases including but not limited muscular disorders, patients with nerve injury, and various neurodegenerative diseases associated with synaptic loss.”


Wang L, Gao J, Liu J, et al. Mitofusin 2 regulates axonal transport of calpastatin to prevent neuromuscular synaptic elimination in skeletal muscles. Cell Metabolism. 2018.

Novel Therapy Delays Muscle Atrophy in Lou Gehrig’s Disease Model [news release]. Case Western Reserve’s website. Accessed July 16, 2018.