Advances in Treating Spinal Muscular Atrophy

Just five years ago, there were no approved therapies to treat the underlying causes of spinal muscular atrophy, a collection of potentially fatal diseases that causes progressive muscle weakness. But in that short time, several advances in research and treatment have been made to help children and adults who have this rare and serious illness.

What Is Spinal Muscular Atrophy?

It’s been called a mysterious disease because it appears differently in different patients. Spinal muscular atrophy, or SMA, is a genetic disease that creates muscle weakness in the body. It is caused by a loss of specialized nerve cells — called motor neurons — that are found in the spinal cord and the brain stem, which connects the brain to the spinal cord. Most of the nerve cells that control muscle movement are found in the spinal cord. When patients have SMA, the muscles do not receive messages from the brain telling them to move, and when muscles don’t move, they atrophy, or decrease in size. This affects muscles needed for sitting, moving your head and in some cases, breathing or swallowing.

Most cases of SMA are caused by a defect or mutation in chromosome 5. This leads to a deficiency of a motor neuron protein called SMN, or survival of motor neuron, which researchers believe is needed for normal motor neuron function.

Types of SMA

SMA is classified in several types, depending on the patient’s age when the disease develops. The younger the patient, the more severe the symptoms.

• Type I is the most common and most severe type of SMA, developing in infants who are younger than six months. They may have difficulty sucking, swallowing and breathing, and their survival depends on their degree of respiratory function.
• Type II is seen in children aged six to 12 months. They may be able to sit independently but are unable to walk independently, and their muscle function may regress when they approach their teenage years.
• Type III SMA, also called Kugelberg-Welander disease, has milder features that show during early childhood and teenage years. Children with Type III SMA can sit and may walk, but ambulation becomes increasingly difficult with age.
• Type IV usually occurs in adults over age 30, with mild to moderate weakness, mild breathing problems and tremors or twitching. Unlike SMA in children, the weakness at this age only affects muscles close to the center of the body, such as the upper arms and legs.

Advances for SMA

In 2016, the Food and Drug Administration (FDA) approved a drug called nusinersen, which helps the body make enough of the SMN protein to compensate for the protein that is missing, enhancing motor function. The drug has had positive outcomes when used by children, and the earlier it was used, the better the outcomes. The drug is given intrathecal (spinal – lumbar puncture is performed each time) every few weeks. It is a lifelong treatment that has provided hope to these children. Researchers don’t yet know the effect the drug may have on adults.

Additional therapies being researched include:

• Replacing or correcting the SMN gene that lacks the needed protein through gene therapy or gene transfer. With this method, a modified piece of DNA from the SMN would be used to infect a cell with new DNA that makes the cell stronger without making the person sick.
• Neuroprotection, which helps restore the function of motor neurons and prevent their death. This approach could be used in combination with gene therapy. One strategy being studied involves developing neuroprotective small molecules that would keep the cells from dying. Another approach is transplanting stem cells to help the motor neurons grow.
• Muscle protection, which is similar to neuroprotection, does not reverse SMA, but can be used with gene therapy to help prevent the muscles from atrophying. Small molecules can help increase the muscle’s ability to contract, and muscle mass regulators can improve muscle strength.

Many of these therapies are still in the very early stages of research, but the research is positive. With a breakthrough medication approved in just the last two years, more advances in treatment are promising.