Mouse study could provide foundation for future human therapeutics
Supplementing a single protein found in the spinal cord could help prevent symptoms of Lou Gehrig’s disease, according to a new study out of Case Western Reserve University School of Medicine. Researchers found high levels of the protein—called mitofusion 2 or Mfn2—prevented nerve degeneration, muscle atrophy, and paralysis in a mouse model of the disease. Since Mfn2 is often depleted during Lou Gehrig’s, the new study suggests supplementing it could be a novel therapeutic approach for the disease.
Lou Gehrig’s disease, or amyloid lateral sclerosis (ALS), is a progressive disorder that devastates motor nerve cells. People with ALS slowly lose the ability to control muscle movement, and are ultimately unable to speak, eat, move, or breathe. The cellular mechanisms behind ALS are also found in certain types of dementia. For the estimated 15,000 Americans living with ALS, the findings offer new hope for ways to delay symptoms.
“We found a way to alleviate age and ALS-related muscular atrophy in our mouse models,” said Xinglong Wang, PhD, associate professor of pathology at Case Western Reserve University School of Medicine. “Amazingly, we could delay ALS symptom onset by 67 days.”
Wang led the study, recently published in Cell Metabolism, in which researchers successfully staved off muscle atrophy and paralysis simply by increasing Mfn2 levels in mouse spinal cords.
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 who underwent heavy sciatic nerve damage benefited from elevated Mfn2 levels.
Said Wang, “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.”
By studying nerve cells collected from the mice, Wang’s team uncovered how Mfn2 offers its protective effects. The researchers found Mfn2 coexists with nutrients in cell structures called mitochondria. Their experiments showed 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—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,” explained Wang.
Cellular transport is not typically in the job description for mitochondria. The ancient cellular structures are well-known to be “powerhouses of the cell”—producing energy that keeps cells running. According to Wang, “this is a novel, previously unrecognized role for mitochondria.”
Specifically, Wang’s team found 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. “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 muscular disorders, patients with nerve injury and various major neurodegenerative diseases associated with synaptic loss.”
The Latest on: Lou Gehrig’s Disease
via Google News
The Latest on: Lou Gehrig’s Disease
- Community steps up to help man battling Lou Gehrig's diseaseon August 16, 2019 at 11:13 pm
BRANDON: RANDY FLOYD WAS DIAGNOSED WITH ALS OR LOU GEHRIG’S DISEASE IN 2012. HE’S SPENT THE LAST SEVEN YEARS LIVING IN THIS HOUSE DOING HIS PART TO HELP FIND A CURE, BUT NOW, HIS BAD LUCK KEEPS ADDING ...
- Prep Sports Notebook: CovCath football player creates own fundraiser for head coach’s brotheron August 16, 2019 at 12:57 am
The money will go to Team “B”elieve, an organization providing support for families battling ALS, also known as Lou Gehrig’s Disease. The teen-ager is doing it because CovCath football coach Eddie ...
- Dying SoCal Activist Champions 'Medicare For All'on August 15, 2019 at 6:57 pm
Barkan, 35, who has amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease, watched from his wheelchair as Massachusetts Sen. Elizabeth Warren described how he and his family had ...
- 'Warrior' with ALS 'Is Not Going to Stop' Coaching Kids — Even Though He Can No Longer Speakon August 15, 2019 at 6:13 am
Then his arm gave out. Fogel, now 48, was diagnosed with Amyotrophic Lateral Sclerosis (ALS), commonly known as Lou Gehrig’s disease, a progressive neuromuscular syndrome. It eventually paralyzed him ...
- Estranged wife of Sept. 11 responder accused of stealing check from charityon August 14, 2019 at 2:32 pm
The Bethpage man, who is battling Lou Gehrig's disease and a variety of 9/11-related medical issues, says the signature on the back of the check isn't even his. "You wouldn't do that to a stranger ...
- Bismarck lawmaker diagnosed with ALS; Keiser to finish term, consider re-electionon August 14, 2019 at 10:15 am
Longtime Bismarck Republican lawmaker George Keiser has been diagnosed with Lou Gehrig's disease but says he will continue his state House term and consider re-election. "According to Mayo (Clinic ...
- Reginald Garfield Cammonon August 13, 2019 at 4:48 pm
passed away at the age of 64 after a ten year battle with Spinocerebellar Ataxia Type 3 and a recent diagnosis of ALS or Lou Gehrig's disease. He was surrounded by his family and close friends. Reggie ...
- Sci-Fi Looking Robotic Neck Brace Could Help Lou Gehrig’s Disease Patients Lift and Move Their Heads Againon August 13, 2019 at 8:40 am
Amyotrophic Lateral Sclerosis, better known as ALS or Lou Gherig’s disease, is a neurodegenerative condition that affects muscle strength and control, eventually leaving patients unable to even ...
- Growing Hope: Woman With ALS Uses Garden To Spread Joyon August 12, 2019 at 3:27 pm
ALS, or Lou Gehrig’s disease, is progressive, stealing its victims ability to move and speak. Well, this woman lets her gardens do the talking. “I like watching my babies grow. Some we planted ...
via Bing News