David Liu's lab shows new base editing SMA therapy could lead to a one-time therapy

The lab of gene editing guru David Liu, Ph.D., is out with new research showing the promise of base editing to treat one of the most common genetic diseases in infants.

The team reported that a one-time base edit of a gene coding for the survival motor neuron protein improved motor function in mice with spinal muscular atrophy (SMA)  and increased their lifespan. Spinal muscular atrophy is one of the leading genetic causes of infant mortality, affecting roughly 1 in 10,000 births. 

The study, published in Science Thursday, examined Liu’s pioneering research into base editing, a method of amending DNA without causing double-strand breaks. The science has already spawned new biotechs developing a suite of gene editing therapies, including Beam Therapeutics, where Liu is a scientific founder. 

In this latest research, scientists from the Broad Institute of MIT and Harvard, The Ohio State University Wexner Medical Center, and the University of Massachusetts Chan Medical School and led by David Liu looked into whether using base editing on the SMN2 gene would improve outcomes in an SMA mouse model. The SMN2 gene is present in all patients with SMA, whereas the more commonly targeted SMN1 gene may be mutated or gone entirely. The results, the researchers say, bode well.

Mice treated with either the researchers’ base editor or Novartis’ approved FDA treatment Zolgensma were found to have no difference in muscle strength, coordination and physical activity compared to healthy mice. The base editing treatment was found to be on par or better at improving motor function compared to Zolgensma and two other FDA-approved SMA treatments, Biogen’s Spinraza and Roche’s Evrysdi.

But the most significant findings came when the novel treatment was combined with Spinraza, showing that the one-two punch could make for a one-time treatment. The researchers found that mice treated with the combination “exhibited normal behavior and vitality well beyond the lifespan of nusinersen only-injected controls.” The hypothesis is that Spinraza, also known as nusinersen, extends the window when motor neurons can be corrected, allowing the base editor more time to work its magic. And unlike most in vivo results, Liu is optimistic that the treatment may be even more effective in humans, where that time window is months, rather than days in mice. 

“One of the real promises of precision gene-editing therapies is the possibility that a one-time treatment can provide a therapy for the lifetime of the patient,” Liu said in a release. Combination therapy is also a pragmatic solution, given that most patients with SMA are likely already on an existing therapy. 

And Liu said he believes that gene editing for SMA may yet improve, as the scientist's prime editing discovery came after the initiation of this latest study. Liu is a scientific co-founder of Prime Medicine, a new biotech looking to turn this technology into new medicines which closed out a $175 million IPO at the end of 2022.

Editor's note: This article was updated to correct that the research focused on the SMN1 and SMN2 genes, not SMA1 and SMA2.