BIOTECHNOLOGY
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pinal muscular atrophy type 1 (SMA1) is a diagnosis no parent wants to hear. The rare genetic disease causes muscle wasting and motor neuron death due to a mutation in the SMN1 gene. Infants are too weak to sit up, and most won’t see their second birthday. The diagnosis for at least 15 babies born with SMA1 is looking different, though, thanks to a clinical trial from Bannockburn, Ill.-based AveXis. Results published last month show that injecting a gene therapy—a healthy copy of the SMN1 gene delivered by an adeno-associated virus (AAV)—has kept the babies, all 20 months or older, alive and kicking (N. Engl. J. Med. 2017, DOI: 10.1056/NEJMoa1706198). Most can now sit up, and some, almost three years old, can even walk and dance. Geneticists have long been enamored with the idea of treating genetic diseas-
Gene therapy came of age FDA is expected to approve the first gene therapy in the U.S. early next year
A model of a hollow adenoassociated virus, which is used to deliver a piece of DNA in gene therapy.
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C&EN | CEN.ACS.ORG | DECEMBER 4, 2017
es like SMA by using a virus to deliver a healthy piece of DNA. But getting the technology to work has been a slow process. Despite decades of research, just two gene therapies have been approved for use in Europe, and none have been green-lighted by the U.S. Food & Drug Administration. The AveXis success story and others like it are now galvanizing the field. Another is Spark Therapeutics’ gene therapy Luxturna, a one-time treatment that allows people with a genetic form of blindness to see better. An FDA advisory board unanimously recommended approval of the drug in October, and the agency is expected to approve it early next year. Spark and BioMarin Pharmaceutical both have advanced gene-therapy programs to restore genes for the missing blood-clotting proteins in people with hemophilia. Across the industry, over 300 gene-therapy trials are ongoing, and hundreds more are recruiting. “What used to be considered a science experiment is about to become reality,” says AveXis CEO Sean Nolan. Numerous challenges remain, however, says Guangping Gao, director of the Horae Gene Therapy Center and Viral Vector Core at the University of Massachusetts Medical School. For one, delivering gene therapy throughout some organs, including the lungs, muscles, and brain, is still difficult. And scaling up manufacturing “will be a hard issue to resolve.” Changing current production methods, which are refined but small scale, could diminish the therapy’s potency. Cost is another concern. Spark has suggested its drug’s onetime price tag could be $1 million. And if a gene therapy doesn’t work the first time, patients are out of luck, since AAV causes an immune response. Some people previously exposed to AAV naturally might also be ineligible for gene therapy. “I am sure we will have some more setbacks,” says Mark A. Kay, a director of the human gene therapy program at Stanford University School of Medicine. But he is hopeful about the number of treatments that people may soon have access to. “It is an exciting time for gene therapy.”—RYAN CROSS
C RE D I T: KAT H ER I N E H IN K EL /U N I V E RS I T Y OF P E NN SY LVA N I A
YEAR IN PHARMA
