Supplementing a protein called mitofusion (Mfn2)—found in the spinal cord—may help prevent symptoms of Lou Gehrig’s disease, according to a study published in Cell Metabolism.

Researchers from Case Western Reserve University School of Medicine found that high levels of the protein prevented nerve degeneration, muscle atrophy, and paralysis in a mouse model of the disease. They suggest that, since Mfn2 is often depleted as the result of the disease, supplementing it could be a novel therapeutic approach.

“We found a way to alleviate age and ALS-related muscular atrophy in our mouse models,” says Xinglong Wang, PhD, associate professor of pathology at Case Western Reserve University School of Medicine, in a media release.

“Amazingly, we could delay ALS symptom onset by 67 days,” adds Wang, leader of the study.

In their study, Wang and colleagues tested the most widely used ALS mouse model. They genetically engineered the diseased mice to have increased Mfn2 levels—but only in nerve cells that extend from the spinal cord and connect to muscle fibers. In late stages of the disease, mice with high Mfn2 levels in these nerves were a healthy weight, and did not have any of the muscle atrophy, gait abnormalities, or reduced grip strength that mice in control groups developed. Even mice that underwent heavy sciatic nerve damage benefited from elevated Mfn2 levels, explains the release, from Case Western Reserve University.

“Upregulation of Mfn2 specifically in nerve cells is sufficient to abolish skeletal muscle loss in ALS and aged mice, despite ALS-causing protein being found in all organs and tissues,” Wang states.

By studying nerve cells collected from the mice, Wang’s team found that Mfn2 coexists with nutrients in cell structures called mitochondria. Mitochondria travel along nerve cell extensions—axons—and deliver the nutrients to the point where nerve cells and muscle fibers meet. This preserves sensitive connections—synapses synapses—between nerve and muscle cells and prevents muscle atrophy.

“We found mitochondria function as miniature ‘trucks’ to transport protein along axons to prevent synaptic degeneration,” Wang continues.

Specifically, Wang’s team found that mitochondria use Mfn2 on their surfaces to carry a nutrient called calpstatin. Calpstatin inhibits harmful enzymes that break down nerves and muscle fibers. With the help of Mfn2, mitochondria carry calpstatin along nerve cells axons to meet muscle cells. There, calpstatin prevents enzymes from destroying delicate synapse connections. But without Mfn2, mitochondria can’t carry the nutrient.

According to Wang, the findings have broad implications, the release continues.

“Mfn2 deficiency or mutations are commonly observed in patients with ALS, peripheral neuropathy, Alzheimer’s disease, and other neurodegenerative diseases in which synaptic loss has long been recognized as a prominent early feature,” he says.

“Supplementing Mfn2 may be a common and effective therapeutic approach to treat a wide range of diseases including but not limited to muscular disorders, patients with nerve injury, and various major neurodegenerative diseases associated with synaptic loss.”

[Source(s): Case Western Reserve University, Science Daily]