Gene Therapy: New Hope for SMA?

Okay, c'mon images of denim and psychotherapeutic couches might be the first things that come to mind when you hear the words “gene therapy.” But what is it really? Gene therapy is a way of using genes, our bodies’ instructions, to treat disease. In the most straightforward of cases, gene therapy is used when the body lacks a working copy of a particular gene. Gene therapy introduces a new, functional copy of that same gene into the body to make up for a dysfunctional one. In this way, gene therapy targets the source of the disease, treating the underlying cause rather than just the symptoms.  

Gene therapy is hardly new; researchers have been working for literally decades to develop these targeted treatments (dare we say, cures?) for genetic diseases. This development has not been without challenges, though. Gene therapy lost the trust of many after the death of a clinical trial participant in 1999, leading many to rightly question its safety. Obstacles that had to be overcome include introducing genes into the correct cells and activating them appropriately, avoiding triggering the immune system which could try to fight off the treatment, and making sure the new gene gets introduced into the existing DNA without disrupting another gene in the process.

Technology has improved though, and gene therapy has experienced a resurgence in the past few years. It has shown promise for the treatment of a variety of conditions including inherited immune deficiencies, hereditary blindness, some cancers, and certain blood disorders like hemophilia. Excitingly, spinal muscular atrophy may soon be added to the list of disorders for which gene therapy is available.

Spinal muscular atrophy, also known as SMA, is an inherited neuromuscular disorder. In SMA motor neurons within the brain and spinal cord break down and die. Motor neurons are the nerve cells that control voluntary muscle movements like sitting, walking, and talking as well as even breathing and swallowing. As this breakdown occurs, the brain loses communication with the muscles, causing muscle weakness and eventual loss of muscle control. Because the muscles are no longer being used, they get smaller and waste away (“atrophy”).

For a genetic disease, SMA is relatively common, affecting about 1 in every 6,000 babies born. The most common type of spinal muscular atrophy is also its most severe—type 1. While babies with SMA type 1 may seem healthy at birth, they develop muscle problems at a young age, typically within their first few month. Newborns with type 1 never learn to sit without being supported. They typically die within the first year or two of life, because they lose the muscle function required for breathing.

Until now, treatment for spinal muscular atrophy has consisted of simply responding to the symptoms that a person has: placing a feeding tube for those with trouble swallowing, prescribing muscle relaxants for muscle spasms, and using a ventilator to help with breathing. A new drug however, attempts to address the genetic deficiency that causes the disease to prevent symptoms from developing in the first place.

But before we talk more about this treatment, let’s back up a little bit. To understand how the drug works, it’s important to understand that SMA is caused by very low levels of a protein called SMN. SMN stands for “survival motor neuron” protein. As its name suggests, this protein is important for the healthy development and longevity of motor neurons. The main gene that is the instructions for the SMN protein is called SMN1. In SMA, SMN1 is altered in such a way that the protein is not created properly.

AVXS-101 is a gene therapy candidate that in a single dose given once a lifetime delivers a working copy of SMN1 to treat SMA type 1. It is not yet clinically available to all patients with the condition, but it is the only gene therapy currently in clinical development for SMA. For this phase of the trial, all of the patients sought to participate have been included. As of last spring, data presented on the ongoing clinical trials with AVXS-101 showed those receiving treatment to have improved motor skills, better feeding and breathing abilities, and potentially longer lifespans. While that time has not yet come and the trials are awaiting more data in the outcomes of their efforts, the possiblity for help is well underway. 

Based on these and other promising results, last week it was announced that the FDA gave AVXS-101 “Breakthrough Therapy Designation.” This designation is given to drugs designed to treat serious or life-threatening diseases for which preliminary evidence suggests that the drug may be a substantial improvement over existing treatments. When a drug is designated in this way, the FDA expedites its review with the intention of shortening the time frame in which safe, effective drugs can become available outside of clinical trials.

For families affected by SMA, this cannot come quick enough. The potential for an effective treatment for such a severe, life-limiting condition has been a long time coming, and its development is sure to bring hope to the SMA community worldwide.

To find out more about this and other clinical trials, visit