Q: Is there a new treatment for spinal muscular atrophy?

A: Spinal muscular atrophy (SMA) is a group of recessively inherited disorders (the patient must inherit a defective gene from both of their parents) that manifest as muscle weakness (for example affecting the patient’s ability to walk, and potentially affecting their ability to breath), occurring in up to one in every 10,000 people. In 1995 the genetic defects that affect the production of the survival motor neuron protein (SMN protein), a deficiency of which causes SMA, was identified. The specific defects in the gene determine which form of the disease (typically characterized by the age where symptoms are identified) is manifested.

SMA type 1 is the most common and earliest onset form (typically by 6 months of age and accounting for about half of all cases), manifesting as severe and progressive muscle weakness, rapidly affecting the infant’s ability to breath. Most babies with this condition die by age 2 due to compromise of the muscles of respiration.

SMA type II (about 20% of cases) has onset between six to 18 months of age, and begins with difficulty sitting up/standing. These patients often die in childhood or early adulthood, again usually due to respiratory illnesses.

SMA type III (about 30% of cases) has onset after 18 months of age up to early adulthood. Although they are initially able to stand and walk, they eventually develop difficulty walking up stairs or rising from a sitting position. Depending on the severity of their symptoms their life expectancy may be limited to adulthood, although some patients with this condition have close to normal life expectancy.

SMA type IV (less than 5% of cases) is not identified until early adulthood, and usually manifests with less severe and more slowly progressive weakness. These patients typically have a normal life expectancy.

The diagnosis of SMA is suspected based on the patient’s symptoms, and is confirmed by genetic testing. Other testing may be done to rule out other diseases whose symptoms may mimic this condition.

Treatment of SMA includes supportive care (including ensuring good nutrition, supporting the patient’s mobility needs, giving appropriate respiratory care, treating complications if and when they arise, etc.), as well as genetic counseling for the parents/family. There is a disease modifying medication (nusinersen, an antisense oligonucleotide which increases SMN protein by modifying the splicing of the gene) which may help symptoms. A genetic therapy is in clinical trials, and although some of the patients in the trial have died (remember SMA type I has a very guarded prognosis), there is now some hope for patients with this severe condition.

Jeff Hersh, Ph.D., M.D., can be reached at DrHersh@juno.com