Shared pathway links Lou Gehrig's disease with spinal muscular atrophy

September 27, 2012

Researchers of motor neuron diseases have long had a hunch that two fatal diseases, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), might somehow be linked. A new study confirms that this link exists.

"Our study is the first to link the two diseases on a molecular level in ," said Robin Reed, Harvard Medical School professor of and lead investigator of the study.

The results will be published online in the September 27 issue of Cell Reports.

ALS, or Lou Gehrig's disease, which has an adult onset, affects neurons that control voluntary muscles. As a result, muscles start to weaken, and patients eventually lose the ability to move their arms, legs and other parts of the body. In contrast, patients who have SMA tend to be infants and young children. Symptoms are similar to ALS, with lack of ability to control muscles being the major symptom. In both diseases, the most common cause of death is the loss of in the chest, resulting in .

Previous studies have shown that one of the causes of ALS is mutation of the FUS gene, and that a deficiency in the survival of motor neuron (SMN) protein causes SMA disease. The SMN protein is present in bodies in the nucleus known as Gemini of Coiled Bodies, or . Reed's lab connected the FUS protein to the SMN protein and the formation of gems in cellular nuclei.

"Nobody really knows what the function of gems are," said Reed. "The consensus so far is that they might be involved in biogenesis of crucial nuclear RNAs."

The researchers arrived at this pathway by studying human fibroblasts, cells that form the basis of connective tissue. "Unlike other studies of ALS and SMA, in which post-mortem tissue is normally used, we used fibroblasts from patients. These cells are easily accessible because they can be obtained from patients' skin and may provide a better idea of what happens in the human body," said Reed.

Reed and colleagues began the study by showing that the FUS protein is essential for normal gem levels. Without it, gem levels in ALS fibroblasts are much lower than in control fibroblasts.

This feature of ALS fibroblasts led the team to connect the disease with SMA. Previous studies had shown that when cells were deficient in SMN protein, fibroblasts also lacked gems in the nuclei. The loss of gems as a final result in both the SMA and ALS pathways led Reed and her team to believe that they might, in fact, be part of one larger pathway.

"The question now is whether the loss of gems is a cause of the disease or a marker for the disease," said Reed.

Reed is hopeful that even if the loss of gems is a marker, it could be used as a diagnostic tool to determine if someone who is presenting symptoms has ALS. "We will need to find out if the loss of gems is applicable to all cases of ALS or if it is specific to ALS patients with mutations in the FUS gene," added Reed.

Either way, Reed describes these finds as killing two birds with one stone. "This common pathway may mean common treatment and resources."

Explore further: New discovery may block ALS disease process

Related Stories

New discovery may block ALS disease process

April 19, 2011
New Orleans, LA –In the first animal model of Amyotrophic Lateral Sclerosis (ALS), developed by Dr. Udai Pandey, Assistant Professor of Genetics at LSU Health Sciences Center New Orleans, Dr. Pandey's lab has found in ...

Researchers find synthetic RNA lessens severity of fatal disease

November 21, 2011
A team of University of Missouri researchers have found that targeting a synthetic molecule to a specific gene could help the severity of the disease Spinal Muscular Atrophy (SMA) – the leading genetic cause of infantile ...

Potential new drug target in Lou Gehrig's disease

November 14, 2011
Two proteins conspire to promote a lethal neurological disease, according to a study published online this week in the Journal of Experimental Medicine.

Disease progression halted in rat model of Lou Gehrig's disease

December 12, 2011
Amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig's disease) is an incurable adult neurodegenerative disorder that progresses to paralysis and death. Genetic mutations are the cause of disease in 5% of patients ...

Recommended for you

Long-lasting blood vessel repair in animals via stem cells

October 23, 2017
Stem cell researchers at Emory University School of Medicine have made an advance toward having a long-lasting "repair caulk" for blood vessels. The research could form the basis of a treatment for peripheral artery disease, ...

Synthetic hydrogels deliver cells to repair intestinal injuries

October 23, 2017
By combining engineered polymeric materials known as hydrogels with complex intestinal tissue known as organoids - made from human pluripotent stem cells - researchers have taken an important step toward creating a new technology ...

Study reveals connection between microbiome and autoimmune disorders

October 23, 2017
Many people associate the word "bacteria" with something dirty and disgusting. Dr. Pere Santamaria disagrees. Called the microbiome, the bacteria in our bodies have all kinds of positive effects on our health, Santamaria ...

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.