Alison Frase remembers the first moment when she thought gene therapy had a chance of curing patients like her son Joshua of a rare genetic muscle disease called X-linked myotubular myopathy. It was 2007, and she was viewing a video of a crippled mouse on her home computer. Four weeks earlier, the mouse had been injected with an engineered virus carrying a new strand of DNA intended to correct a genetic mutation that made its muscles limp and weak.

Frase watched in awe and began to cry as the mouse’s limbs started to twitch. Eventually, it picked itself up and walked for the first time. “I thought, who cries watching a video of a mouse?” she recalls.

Now, thanks to Frase and others, the same treatment is about to be tested in humans. In recent years, gene therapies have become safer and better at hitting their intended targets in the body, leading to a handful of remarkable cures in clinical trials. Advocates for rare-disease patients—especially determined parents like Frase—are increasingly seeking to start gene-therapy programs. They are establishing patient advocacy organizations, raising money for research, and even founding their own biotechnology startups to find treatments where few or none currently exist.

Gene therapy is an experimental technique that attempts to replace a disease-causing gene with a healthy copy. Because many rare diseases are monogenic—caused by a mutation in one gene—the approach could potentially be used to treat any disease where the precise genetic mutation is known.

“The prospect of being able to correct these genetic abnormalities with gene therapy has become a topic of great interest in the rare-disease community,” says Mary Dunkle, vice president of educational initiatives at the National Organization for Rare Diseases. “The idea of being able to ‘cure’ a rare disease by addressing the underlying problem is alluring.”

Joshua Frase’s X-linked myotubular myopathy was diagnosed shortly after he was born in 1994. Cases vary in severity, but many affected children die before age two. Alison Frase began researching the disease but found only a handful of published studies, and patient advocacy organizations didn’t know much about the disorder at the time. So in 1996, she and her husband, Paul Frase, a former NFL football player, created the Joshua Frase Foundation to raise awareness.

Eventually, Frase partnered with Alan Beggs at Harvard to establish a patient registry and encourage families to participate in medical research. Beggs’s lab was collaborating with a group at the nonprofit Généthon in France when researchers sent her the video in 2007. Mice had been engineered to carry a mutation in MTM1, the gene involved in X-linked myotubular myopathy. Alterations in that gene disrupt the role of a protein called myotubularin, which is involved in muscle-cell development.

After the mouse experiments, Beggs and his colleagues published a study in 2010 that identified a group of Labrador retrievers with an MTM1 mutation, which displayed muscle weakness similar to symptoms in children with X-linked myotubular myopathy. Frase tracked down the owner of one of the dogs, named Nibs, in Canada. Back in the U.S., Nibs became the start of the first dog colony for myotubular myopathy, which the Joshua Frase Foundation helped fund.

The dogs became central to research by Martin Childers, a professor of rehabilitation medicine at the University of Washington. Childers, who has been working with Beggs and the Généthon group to develop and test gene therapy in the dogs bred from Nibs, says the results have been remarkable. “We were able to find a dose that completely reversed the disease in dogs. You could not tell the difference between the dogs with this fatal disease and the normal ones,” he says. The findings were published in February.

A San Francisco company, Audentes Therapeutics, has licensed the technology and says it will begin a clinical trial this year. It will be the first human gene-therapy trial for X-linked myotubular myopathy.

Joshua died in 2010 at age 15, having lived years longer than his doctors expected. Though he will never be able to benefit from the therapy, Alison Frase hopes her years of advocacy will be able to help other children.

Alison Frase, with her son Joshua at age five in 2000, first learned about gene therapy more than 10 years ago.

Racing toward a cure

Historically, much of the research on rare diseases has been driven by patients and patient organizations that have raised funds for grants and reached out to medical researchers, says Dunkle. “It’s not surprising that parents of children with devastating diseases would be doing whatever they could to try to save the lives of their children,” she adds. “For them, the clock is ticking, and there is a powerful sense of urgency.”

Ilan Ganot knows that feeling well. He’s determined to cure his six-year-old son Eytani of Duchenne muscular dystrophy, a degenerative muscular disease, and he thinks gene therapy could be the way to do it. Most boys born with the disorder only live into their 30s.

A former J.P. Morgan banker, Ganot moved his family from London to the Boston area, raised $17 million, and in 2013 founded Solid Biosciences to develop drugs for Duchenne. The company considered more than 200 different treatment approaches before making gene therapy its top priority.

Its therapy aims to restore dystrophin, a key protein that keeps muscles intact, which is missing in Duchenne patients. The dystrophin gene is too large to fit inside a traditional engineered virus, a problem that hindered previous efforts to develop gene therapy for the disease. So the company is using what it calls “micro-dystrophin,” a DNA sequence that acts like the full-size gene but is small enough to fit inside a virus. Ganot says he hopes to begin clinical trials of the therapy this year.

The promise of gene therapy

Patient advocate Laura King Edwards is excited about gene therapy for its potential to correct disease at its root, even though it might not come in time to save her 18-year-old sister, Taylor, who has an extremely rare and fatal neurological disorder called Batten disease. “The beauty of gene therapy is that to a certain extent you can put any gene into a viral vector and get it to the gene you need to fix,” says Edwards.

Taylor was a thriving seven-year-old when her condition was diagnosed in 2006. For years, she continued to excel in school, ran 5Ks, and competed in talent shows, Edwards says. Now, she is blind and has lost the ability to walk or communicate.

The same year as Taylor's diagnosis, Edwards and her mother, Sharon King, founded a patient advocacy organization called Taylor’s Tale to focus on the disease. In 2011, King connected with a young researcher named Steven Gray at the University of North Carolina at Chapel Hill, whose lab was working on gene therapy for other rare diseases. Two years later, Taylor's Tale and other organizations raised enough money to fund a grant for Gray to expand his work on gene therapy for Batten disease.

Dallas-based Abeona Therapeutics licensed the technology from Gray’s lab last September and is now moving toward clinical trials.

Gray says rare-disease patients and their families are becoming interested in gene therapy because of recent successes in clinical trials of other rare diseases.

“I’m seeing a transformation where there’s a sense of patients and patient advocates being enabled to fight for the development of new treatments,” he says. And as the falling costs of genetic testing make it possible to diagnose these conditions at ever younger ages, Gray says, there’s an opportunity to intervene early.