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Spotlight on Gene Therapy: finding a Cure

Every day is ALS awareness day

Tuesday, May 31, 2016
By:  Florie Borel

Let's keep talking about ALS!

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).

There is currently only one FDA approved treatment, that prolongs life only by a few months. Patients need better treatments!

Our Latest Research

We silence the SOD1 gene using an artificial miRNA, called miR-SOD1. We simply took an endogenous miRNA, and engineered its sequence to allow for specific silencing of SOD1. We deliver miR-SOD1 in the CSF using an adeno-associated viral (AAV) vector. AAVs have been used in many clinical trials, and one AAV-based gene therapy is approved in Europe. We chose to use AAVrh.10, which has already been tested in several CNS clinical trials and has a demonstrated safety profile.

We tested this treatment on a transgenic ALS mouse model expressing mutant SOD1G93A protein. 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 

In mice

Silencing of SOD1 in adult SOD1G93A transgenic mice profoundly delayed both disease onset and death in the SOD1G93A mice, and significantly preserved muscle strength, motor and respiratory functions.

In conclusion, the study shows a therapeutic effect of silencing the SOD1 gene in systemically treated adult ALS mice.

In non-human primates

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.

In conclusion, this study supports the view that rAAVrh.10-miR-SOD1 merits further development for the treatment of SOD1-linked ALS in humans.

Read all the results

Read a full version of our publication "Therapeutic rAAVrh.10-mediated SOD1 silencing in adult SOD1G93A mice and non-human primates", that was highlighted in the January issue of Human Gene Therapy.