SMN1 Gene Replacement
SMA is caused by mutation of the SMN1 gene. Researchers think that we may be able to treat SMA by replacing this faulty gene.
A type of treatment known as gene therapy, or gene transfer, is thought to be a viable option for restoring the SMN protein that is lacking in people with SMA. As well as replacing SMN1, gene transfer, targeting other important genes, could also be used to provide additional protection to motor neurons, the main cells affected by SMA.
How Gene Therapy Works
Gene therapy uses short pieces of DNA from genes, for example SMN1 for SMA. As it is not possible to insert the gene directly into a cell, scientists use a carrier called a vector to deliver the gene to the human cells that need it. For human gene therapy, harmless viruses are the vectors used to ‘infect’ the cells with the new DNA. Importantly, the viruses are modified so that they are not contagious and cannot cause disease.
Gene Therapy Challenges
The main cells affected by SMA, the lower motor neurons, are found in the spinal cord. This means vectors have to cross the blood-brain barrier in order to reach these target cells. The blood-brain-barrier is a semi-permeable covering that protects the brain from foreign substances and maintains a constant brain environment. Finding gene transfer techniques that can cross this barrier presents a real challenge.
The importance of virus delivery route is discussed at the Cure SMA research conference 2014:
Separate published studies from the laboratories of Dr. Brian Kaspar, Dr. Martine Barkats, and Prof. Mimoun Azzouz show that the adeno-associated virus type 9 (AAV9) is able to cross the blood-brain barrier and produce SMN protein, resulting in drastic improvements in SMA model mice: