Spotlight on Gene Therapy: finding a Cure

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease and survival in ALS is typically 3-5 years. No treatment extends patient survival by more than three months. Approximately 20% of familial ALS and 1-3% of sporadic ALS patients carry a mutation in the gene encoding superoxide dismutase 1 (SOD1).

Our Research

In a transgenic ALS mouse model expressing mutant SOD1G93A protein, silencing the SOD1 gene prolongs survival. The study shows a therapeutic effect of silencing the SOD1 gene in systemically treated adult ALS mice. In addition the same vector was tested in monkeys to assess whether the vector can also silence the SOD1 gene in a larger animal, and therefore to assess whether this therapy can be translated to patients.

The Results 

Our research shows a silencing method based on an artificial miRNA termed miR-SOD1 systemically delivered using adeno-associated virus rAAVrh.10, a serotype with a demonstrated safety profile in CNS clinical trials. Silencing of SOD1 in adult SOD1G93A transgenic mice with this construct profoundly delayed both disease onset and death in the SOD1G93A mice, and significantly preserved muscle strength, motor and respiratory functions.

The results also show that intrathecal delivery of the same rAAVrh.10-miR-SOD1 in non-human primates significantly and safely silences SOD1 in lower motor neurons. This study supports the view that rAAVrh.10-miR-SOD1 merits further development for the treatment of SOD1-linked ALS in humans.

Read a full version of our publication "Therapeutic rAAVrh.10-mediated SOD1 silencing in adult SOD1^G93A mice and non-human primates", that was highlighted in the January issue of Human Gene Therapy.

Pubmed: http://www.ncbi.nlm.nih.gov/pubmed/26710998

Interested in collaboration or partnership?