Which do you think would win in a fight between gene editing and gene therapy?
Well, we might find out sooner than expected, because Vertex Pharmaceuticals (VRTX -0.44%) has doubled down on a partnership with gene editing pioneer CRISPR Therapeutics (CRSP 1.25%). Vertex didn't end its spending spree with exclusive rights to potential new muscular dystrophy treatments from CRISPR; it also splurged on a privately held gene editing start-up with a promising preclinical-stage Duchenne muscular dystrophy (DMD) candidate.
While Vertex and CRISPR do their best to repair genes, a gene therapy from Sarepta Therapeutics (SRPT 3.52%) is gaining steam. Here's the distilled version of arguments for both methods.
The case for Vertex's gene editing approach
DMD is a rare inherited muscle-wasting disorder that's caused by a lack of a functional dystrophin gene, which produces a structural protein that anchors muscle cells to the scaffolding between each other. Without functional dystrophin, patients begin having trouble walking at 3 to 5 years of age, and few ever celebrate a 40th birthday.
Vertex and CRISPR are trying to restore dystrophin function by licensing everything CRISPR produces related to treating DMD. Vertex also licensed rights to another muscle-wasting disorder called myotonic dystrophy Type 1 (DM1), which involves a repeating sequence of three nucleotides that disrupt another gene vital to muscle activity.
Gene therapies that insert a functioning version of genes are problematic when it comes to dystrophin because it's the longest human gene there is. It's a whopping 2.3 million base pairs long, but just less than 1% is used to make dystrophin. The important bits aren't in a few locations, either; they're separated into 89 segments found along the entire length of the gene.
Since the entire dystrophin gene won't fit into any of today's delivery mechanisms, CRISPR and Vertex think the best approach is a treatment that enters muscle cells and repairs the problematic sections on the fly. At the moment, CRISPR doesn't have a DMD candidate to speak of, but the privately held company that Vertex bought for $245 million up front, Exonics Therapeutics, does. In studies with large animals, Exonics has already used CRISPR to repair and restore dystrophin.
Vertex is going to run Exonics as a subsidiary and pay the former owners up to $1 billion if their DMD and DM1 programs pass specific milestones. That's nothing to sneeze at, but it could be well worth it if the DMD program succeeds in upcoming human studies.
The case for Sarepta's gene therapy approach
Vertex and CRISPR haven't actually edited any DNA in human muscle cells yet, but Sarepta's approach to treating DMD has already exceeded expectations. In March, Sarepta shares soared after the company reported early results from the first four patients treated with AAVrh74.MHCK7.Micro-dystrophin, a gene therapy that inserts a functional micro-dystrophin gene.
Sarepta's approach isn't supposed to produce perfect dystrophin, but investigators were right to expect that the addition of functional micro-dystrophin would help the whole scaffolding hold together. After 270 days, the effects were clearly visible in biopsy samples. Also, two patients knocked a significant amount of time off their best 100-meter sprint, and the other two held steady.
All four children who received Sarepta's micro-dystrophin candidate are developing abilities, instead of losing them as expected. If an ongoing 24-patient placebo-controlled phase 3 trial proves that Sarepta didn't accidentally pick the four healthiest DMD patients of all time, micro-dystrophin could enter the market before Vertex can show us any meaningful data from its gene editing program.
Room for both
Editing the big dystrophin gene in multiple locations as Vertex intends might produce complete dystrophin that's fully functional, but there are some big drawbacks. There are heaps of potential mutations along the dystrophin gene that result in DMD, which means Vertex will probably be able to reach just a fraction of the small patient population with any one treatment.
While Vertex's method might prove more effective for a limited audience, Sarepta's micro-dystrophin therapy could become entrenched before Vertex gets a chance to enter the market with a gene-editing treatment aimed at a limited portion of the DMD population. Sarepta's gene therapy might not be the best way to fix every case of DMD, but it's probably going to do a lot more for investors portfolios over the long run.