Researching neuromuscular disorders and treating children afflicted by them was not the path intended by Tom Crawford. After studying psychology and religion at Yale College, he consid­ered pursuing a career in science. He felt conflicted, however, because in the 1970s science seemed dedicated solely to supporting the military-industrial com­plex—not his cup of tea. After exposure to the hospice movement, he connected with the challenges hospice physicians faced and got onboard by going to medi­cal school at the University of Southern California.

“At the time, you would never let anyone with a fatal disease know they were dying,” says Crawford. “The hos­pice movement advocated for folks in that awful position, saying they have as much right as anybody else. So, I said, ‘OK, I’ll be a hospice doc.’”

That prompted medical school and a rotation in internal medicine that, he says, did not resonate. His next rotation, in pediatrics, was far from his ambition: “I told my to-be wife and others that pe­diatrics was the one specialty I know I’m not going to do.”

Then, after admitting a patient with spinal muscular atrophy (SMA), the sun broke through the clouds. Characterized by the loss of motor neurons in the spinal cord and lower brain stem, the disease results in progressive muscular atrophy and weakness. In the most severe cases, patients may become paralyzed and have difficulty performing basic functions of life, such as breathing and swallowing. Many do not survive.

“It changed my life,” Crawford says. “This may have been the first baby I ever held, and yet he was admitted to the hos­pital to die. That did something to me.”

During rounds the next morning, Crawford explains, the attending physi­cian described SMA as a hopeless dis­ease, and suggested they not disturb the grief-stricken mother. Crawford felt dif­ferently: “I felt we were isolating her—it was exactly the wrong reaction.”

The experience segued into a calling to care for kids seen as unattractive or off-putting in ways—kids with neuro­logic problems. Like the mom of the baby with SMA, parents felt ostracized because their children were different.

“Nobody felt comfortable being around them, they didn’t know what to say,” says Crawford. “But that’s where being a normal human being has thera­peutic impact. I found my niche.”

That niche led to training in pediatric neurology and a fellowship in neuro­muscular disorders at Johns Hopkins. With no cure for SMA, Crawford ini­tially focused as much on the lives of patients and parents as on the disease itself. At the heart of his work, he pro­moted ways to further patients’ devel­opment—no easy challenge for patients with neuromuscular disease and parents who perceive their world as perilous.

“It’s a very weird process to ask par­ents to push a kid out the door, to take chances, and kids with profound muscle weakness are less inclined to press the issue because they also need help with so many routine things,” says Crawford. “Yet it’s essential for their self-identification, to do something on their own, to get in trouble—that is part of growth, part of normal.”

That normal leads to confidence and success for patients, says Crawford, pointing to higher college graduation rates and postgraduate degrees among kids with SMA than their peers in the general population. He points to Brynne Willis, a patient he diagnosed at age 10 who now at 25 is pursuing a master’s degree in mental health at The Johns Hopkins University to help patients and families manage disabilities the way Crawford has managed her.

“I’m learning from my own experi­ence in treating children and families with disability and chronic disease,” says Willis.

For the parents, Crawford says, the struggle is taking on so many unnatural roles: “They become the medical man­ager, the coordinator of therapy services, drugs and doctors, and at the same time they feel a sense of bewilderment, guilt and grief all at once. Parents need some­one to say they’re OK, that the tensions they are feeling are normal.”

Addressing such quality of life issues became Crawford’s mission, but along the way he also found science again in studying SMA and other neuromuscu­lar disorders. On the one hand, he could help patients become more independent and parents lighten their reins as dis­ease managers. On the other hand, he could explore innovative new therapies through developing and participating in clinical trials.

Research gains against SMA were modest over the first part of his career, but this has changed dramatically during the last decade, culminating last summer when SMA researchers celebrated Food and Drug Administration approval of the first drug, called Spinraza, to treat SMA. Injected into the fluid surround­ing the spinal cord, the drug demon­strated startling effects in clinical trials. Most patients treated with Spinraza reached measurable motor milestones such as head control, sitting, standing or crawling—an unprecedented outcome.

Recalling cellular studies of Spinraza that began in 2006, animal studies in 2009 and human trials in 2013, Craw­ford says, “Every step was, ‘Oh my God, it works.’”

Another recent breakthrough came in the form of a gene transfer therapy de­veloped by a company named AveXis. This approach involves administration of a normal human SMA gene packaged in a clinically benign viral coat called AAV9. In a phase 1 trial of 12 infants with SMA1—the worst form of SMA (patients are expected to die or require full-time ventilation before their first birthday)—researchers at Nationwide Children’s Hospital in Columbus, Ohio, demonstrated improvement in motor function for all patients, with nine out of 12 sitting independently.

“These babies are doing spectacu­larly,” says Crawford. “We’re seeing lots of walkers and sitters,” he adds, noting that Johns Hopkins is one of the sites for a new multicenter trial with the therapy.

These treatments have galvanized motor neuron research, Crawford ex­plains, but they are coming with a high price tag. Spinraza costs $750,000 per patient in the first year alone. Crawford has developed a newfound appreciation for people such as Redonda Miller, The Johns Hopkins Hospital president, and Ted Chambers, administrator for the Department of Pediatrics, who have been striving to make these treatments accessible to patients.

“The development of a research pro­gram is no longer just scientists and clinicians trying to cobble something together that can pass FDA muster,” says Crawford. “Programs will require the entire administration to make it work. We have new barriers to getting meaningful therapy to those who can benefit from it, so they are now part of the research team.”

For his part, Crawford takes no own­ership of the SMA breakthrough: “I know that I helped at lots of phases of the research, but it feels really awkward to make it about me. I’d like to think I’ve played a role in keeping the focus on what matters.”

For him the reward is the longitudinal relationships he has built with patients and parents over the years, and observing their towering achievements against the odds: “I presently remain very bullish on making these kids’ lives work despite profound muscle weakness. We’re much better at managing this disease—we’re doing better pulmonary, orthopedic, nu­tritional and supportive therapies than we ever did before.”