MyoDys45-55

Duchenne muscular dystrophy (DMD) is a devastating muscle disorder in which there is a clear unmet need for disease modifying therapies. Treatment strategies to restore the dystrophin protein (that is otherwise lacking in Duchenne patients) will stabilize or slow disease progression. We have developed MyoDys45-55, a gene editing therapy that can restore a functional dystrophin protein in DMD patients and significantly improve the quality of life and lifespan. This therapy is applicable for approximately half of all patients.

Advantages

• Leads to a permanent reversal of the mutation in the patient’s own gene

• Applicable to 50% of all Duchenne patients

• Associated with one of the mildest clinical phenotypes and thus is expected to lead to a more stable dystrophin protein

• Prevent muscle cell loss and increase lifespan for DMD patients

How it Works

MyoDys45-55 is a gene editing platform designed to permanently delete a region of DNA where there is a hotspot of Duchenne mutations and restore dystrophin protein. The dystrophin protein normally protects muscle cells and the loss of dystrophin causes the muscle cells to die.

The exons in normal DNA fit together like puzzle pieces.

Duchenne DNA contains genetic mutations which prevent the exon puzzle pieces from fitting together, leading to loss of the dystrophin protein.

This deletion allows the puzzle pieces to fit together, producing a shortened, internally deleted but functional dystrophin protein.

Why this Target

This region is advantageous to remove since this deletion is associated with one of the mildest disease courses seen in human Becker muscular dystrophy patients. Some Becker patients with an exon 45-55 deletion have been found to be asymptomatic into their 60s. Additionally, this region encompasses a hotspot of ~50% of all Duchenne patient mutations meaning a large number of Duchenne patients (approximately half) could be treated with this drug.

Why Gene Editing

Gene editing offers advantages over other dystrophin-restoration strategies because:

• It’s permanent

• It modifies the patient’s own DNA sequence

• It allows the majority of the gene to remain intact

Proof so Far
MyoDys45-55 has been demonstrated to restore dystrophin via CRISPR/Cas9 gene editing in human stem cells and in mice. Further pre-clinical development is ongoing.