Gene Therapy in fALS mice.

A major challenge in neurological gene therapy is delivery of the transgene to sufficient cell numbers in an atraumatic manner. This is particularly difficult for motor neuron (MN) diseases that have cells located across the entire spinal cord, brain stem, and cortex. The group of Prof. Patrick Aebischer (LEN - Neurodegenerative Studies Laboratory) used the familial mouse model of amyotrophic lateral sclerosis (ALS) to examine the feasibility of body-wide intramuscular injections of adeno-associated virus serotype 6 (AAV6), a vector capable of axonal retrograde transport, to deliver therapeutic genetic information across the lower MN axis. Their results stress the complexity of gene delivery for human mutant superoxide dismutase 1 (mSOD1) silencing and suggest that critical thresholds of protein knockdown and transduction across various cell types are required to translate local neuroprotective effects into functional improvements.

Chris Towne et al., Molecular Therapy; doi:10.1038/mt.2010.260 (2010)