A breakthrough study revealed that reversing muscle damage in children affected with ‘floppy baby syndrome’ or spinal muscular atrophy, the leading genetic cause of death in children, may be possible with a protein boosting drug.
Spinal muscular atrophy, caused by a genetic defect that abnormally codes the SMN protein, which plays a crucial role in the survival of motor neurons leading to the wasting of voluntary muscles in the arms and legs of infants and children, affects one in 6,000 births, according to statistics from Families of SMA Community.
Doctors have previously known that the disease targets the body’s nerve cells, causing those affected to have little or no control over their movements. Researchers at the University of Edinburgh conducted a study on mice, and found that the disease not only causes nerve damage, but also reduces the blood supply to muscle tissue.
Scientists previously thought that the muscle damage was a result of the nerve damage from the disease, however researcher revealed that the muscles in the mice affected with SMA started to weaken even before the nerves deteriorated.
Additionally, not only are the muscles damaged by having low levels of the SMN, researchers found that the genetic mutation which disrupts of the muscles’ blood supply and leads to further muscle damage.
Researchers treated SMA-affected mice with histone deacetylase (HDAC) inhibitors, commonly used in psychiatry and neurology as mood stabilizers and anti-epileptics and increasingly for cancer and inflammatory disease treatments, and found that the drug increased the levels of SMN protein in the muscles of the mice by targeting the genetic mutation.
"Spinal muscular atrophy is the most common genetic cause of death in children. By showing the important role that muscles play in this disease, we can now focus our efforts on trying to block the disease in all affected tissues of the body," lead author Tom Gillingwater, professor of neuroanatomy, wrote in the study.
Previous studies have shown that a histone deacetylase drug called suberoylanilide hydroxamic acid, under the brand name Zolinza, was shown to increase the lifespan in SMA mice. The drug is already approved by the US Food and Drug Administration for particular cancers, making it easier to be tested for people with other conditions.
There are three levels of spinal muscular atrophy, the disease affects movement but does not affect mental abilities.
Type I has the most severe and earliest onset of symptoms which is usually observed at birth, and is characterized by babies with floppy limbs, “flickering” tongues, severely impaired breathing along with swallowing difficulties.
Type II is generally noticed in early childhood, with less severe but still disabling symptoms like problems with walking, less severe respiratory problems and can often survive into adulthood.
Type III is the least serious form of the disease, and children in this category are usually diagnosed after the age of two. Children have trouble walking and standing alone, their fingers may tremble, and they are at an increased risk for respiratory infections.
However half of those affected with the most severe form of SMA die before the age of two, and there is no cure, only therapy and support to help manage the condition.
The organization predicts that about 7.5 million Americans are carriers of the gene that causes SMA, about one in every 40 person in the United States.
The findings were published on Monday in the journals of Human Molecular Genetics and Neuromuscular Disorders.