Study discovers best
way to deliver gene therapy for Sanfilippo Type C
the Sanfilippo Children’s Foundation awarded AUD$90,000 towards a project to
improve delivery of gene therapy to the brain for Sanfilippo Type C. This
project was led by Dr Brian Bigger at the University of Manchester, and the
project is now completed.
researchers compared three different types of a harmless virus called AAV,
which is used to deliver the missing gene in gene therapies. In mice they found
that a new AAV called AAV-TT appeared to work better than those currently in gene
therapy clinical trials (AAV9 and AAV rh10). This new virus spread more evenly
throughout the brain which is very important for any gene therapy for
Sanfilippo Type C.
Type C is more challenging to treat than other subtypes because the enzyme that
is missing – HGSNAT – anchors itself inside the cells of the brain and it
cannot travel to neighbouring cells and treat them. For this reason, achieving
maximum and even distribution of virus throughout the brain is essential.
task was to investigate the best method of injection for optimal distribution
throughout the brain. They used artificial brain models in the lab and
travelled to New Zealand to study the brains of sheep. From this research they
have learned how quickly to inject the AAV for the best distribution and what
area of the brain to target.
studies used AAV to deliver a gene that contains the instructions to produce a
fluorescent protein. This was useful for visualising exactly what cells of the
brain the virus was reaching after it was injected. The next step will be to use
the knowledge gained here to complete preclinical testing of AAV delivery of
the Sanfilippo Type C gene (HGSNAT), prior to initiating clinical trial, which
could start in the next 2 to 5 years. This research could also help improve
gene therapy for other types of Sanfilippo and other genetic diseases that
affect the brain.
project was co-funded by the Sanfilippo Children’s Foundation with Jonah's Just
Begun in the USA and the H.A.N.D.S consortium.