Emerging Gene Therapies for Spinal Muscular Atrophy

Uploaded by DNALearningCenter on 30.07.2012

we're sitting here at a moment in time where we are truly realistic and our
expectations that disease-modifying treatment
might soon be available as such.
And part of that is predicated on our true understanding of the molecular
genetics that underlie this disease.
There are two genes
that are involved in this disease.
Survival of motor neuron one, SMN1,
is the gene that when mutated causes spinal muscular atrophy.
But in the human genome there is another gene, an inverted duplication of the
first gene.
We call it SMN2
and it is almost identical to the SMN1 gene. It has one critical
in a part of the gene that interferes with the splicing
of the RNA
so that we have
an effective protein being synthesized. So the SMN2 gene unlike the
SMN1 gene
makes the full-length protein only about ten percent of the time,
and the other ninety percent of the time it makes a protein that is shorter
than normal, recognized as abnormal and rapidly degraded as such. So the patients
in a way are developing spinal muscular atrophy because they have the
SMN2 gene. But,
it also now provides us with a wonderful opportunity to intervene
potentially with the disease-modifying gene by correcting the splicing
error in the SMN2 gene and making it increasingly like an SMN1 gene,
as such.
So on the one hand, SMN2 allows humans to have
spinal muscular atrophy,
but it also creates an opportunity now for us to therapeutically intervene
and to effectively treat or cure spinal muscular atrophy.