want to “diminish the significant impairment” SBMA causes in some patients; but that their findings suggest that “in the majority, SBMA follows a relatively benign course with comparatively good functional status years after the diagnosis.”

defects in the growth and maintenance of nerve fibers, or “axons,” which carry chemicals from cell to cell, are the primary problem in chromosome- 5 SMA and are a potential point of intervention in its treatment. They published their findings in the April 25 issue of Science.

Chromosome- 5 SMA, a genetic disease in which spinal nerve cells that control voluntary muscles (motor neurons) are lost, is caused by mutations in the SMN1 gene that result in varying

Researchers at several German and degrees of deficiency of the nerve-cell U.S. institutions recently announced protein SMN. they’ve identified a protein that can People with moderate SMN loss have almost completely compensate for weakness and limited mobility but gen-the genetic defect that causes chro- erally live into adulthood, while babies mosome-5-linked spinal muscular born with almost no SMN have severely atrophy (SMA), which is by far the compromised breathing and swallowing most common type of the disease. functions and often don’t survive more They say their findings may open than a few years. new treatment pathways, as well as Wirth’s team identified six families in provide better understanding of the which some of the females with specific biology of SMA and possibly other, SMN gene mutations and protein levels related diseases. had the expected SMA symptoms, while

A research team coordinated by others with the same SMN mutations Brunhilde Wirth at the University of and protein levels had very mild disease. Cologne in Germany identified the Suspecting the presence of modifying activity level of the gene for the plas- genetic factors, the researchers mea-tin 3 protein as a modifying factor in sured activity levels of the siblings’ other SMA in females. genes.

In the process, they found that Only one gene, carrying the code for the protein plastin 3, showed significantly different levels of protein-producing activity in cells from mildly affected, compared to more severely affected, siblings.

In boys, the level of plastin 3 protein didn’t make a difference in the degree of severity of SMA; but in the girls, high plastin 3 protein levels resulted in far less severe SMA symptoms or no symptoms at all with the same degree of SMN deficiency. The investigators don’t know the reason for this gender difference. Further experiments in human cells and in mice and zebrafish showed that plastin 3 is important for bundling filaments that make up nerve axons and

Brunhilde Wirth and colleagues found high plastin 3 levels seem to reduce the severity of SMA in females. ^{that extra plastin 3 can almost} Elsewhere, Eugenio Mercuri’s research team saw motor ^{completely compensate for the} function improve with albuterol in children with SMA2. detrimental effects of reduced

SMN protein levels on these cellular structures.

The researchers note that their findings “support the view that axon biology is crucial for SMA ... and that proteins stabilizing the axon can modify the disease.”

 

Eugenio Mercuri from Catholic University in Rome, with researchers from several Italian institutions and the Dubowitz Neuromuscular Centre in London, found daily treatment with oral salbutamol (called albuterol in the United States) yielded some encouraging results in a small trial involving young children with type 2 spinal muscular atrophy (SMA2).

The investigators, who published their findings online June 23 in Neuromuscular Disorders, gave albuterol at a dosage of 2 milligrams three times a day for a year to 23 children who were between 30 months and 6 years old at study entry.

They assessed motor function using a standardized rating scale six months before the treatment started, when the treatment started, six months after starting treatment and a year after starting treatment.

There were no significant changes in function when the children were not on treatment, but the functional scores after six months and a year of treatment with albuterol were significantly higher than those recorded when the children started albuterol. There were no major side effects.

The researchers say their results suggest albuterol may be beneficial in SMA2 but that a larger trial, in which albuterol is compared to a placebo (inactive substance), is needed to confirm these early findings.

They also note that the drug’s actions in SMA are not well understood. It may reduce muscle wasting and/or increase production of the SMN protein, which is insufficient in this disease.