From heartbreak to hope: a family’s journey through SMA and scientific breakthrough

March was colicky and screamed her first three months of life. But her parents, Wes and Kelly, were thrilled.

“I mean her ab muscles were working overtime,” Kelly said with a laugh.

March was strong enough to cry loudly. 

It was a reassuring sign that she wasn’t showing symptoms of spinal muscular atrophy (SMA), a rare neurodegenerative disorder that causes progressive muscular weakness in infants. Spinal Muscular Atrophy is caused by a lack of survival motor neuron protein and occurs in around 1 in every 11,000 births in the United States. 

March, who was diagnosed with SMA when Kelly was 20 weeks pregnant, was the only patient in a groundbreaking clinical trial led by St. Jude Children’s Research Hospital® that explored treating SMA in utero with the orally administered drug risdiplam. This clinical trial, which now serves as a beacon of hope for other families, grew out of the family’s own heartbreaking history with SMA.   

‘No hope they could give’

When Wes and Kelly started their family “it was all like a Norman Rockwell painting,” Wes said. They had a new home with a picket fence in a nice subdivision and had no trouble conceiving. The pregnancy was smooth. 

They had their first child, a son named Graham, who was a robust little boy with Wes’ cheeks and Kelly’s eyes. Everything seemed to be going well until they noticed signs of weakness at 4 months old. Graham didn’t roll over as he should. By the time he was 6 months old, he had trouble holding his head up and sometimes had trouble swallowing. They received his SMA type 1 (SMA-1) diagnosis at his six-month-checkup, when their pediatrician sent them to neurologists at their hometown hospital. 

“They told us there was nothing they could do, no hope they could give,” Wes said. “They did have clinical trials that were running, but there were age cut-offs, and we’d gone past those, so we left that appointment that day in hospice care.”

SMA-1. They’d never heard of it. And they hadn’t known that each of them carried genetic traits that increased the chances of their biological children having the debilitating disease.  

SMA-1 is the most common and severe form of the disease. Left untreated, it results in progressive muscle weakness that leads to death typically before the 2nd birthday. 

Kelly stayed home with Graham, caring for him as he began to lose the ability to cough and swallow, and hooking him up to breathing machines when he began to lose the ability to breathe on his own. After the diagnosis, they had 10 months with him until he passed away in August 2016. 

“I wish this wasn’t my story. I wish I didn’t know what SMA was. But since it is, I feel like we have to tell it, we have to let people know,” Kelly said.

Losing Graham left them so bereft they relied on family and faith to get through, and the online SMA community of friends, some of whom they’d never met, but who understood their grief in a way few others could. 

New possibilities

The couple adopted twins two years later. They’d done enough reading on the genetic impact their combined traits would have on biological children, so they felt it was safer to adopt. 

Wes and Kelly were gradually building the kind of happy, full family life they’d dreamed of. The twins turned 4, and their lives were busy with preschool, playdates, church and family.  Kelly remained active in online SMA groups and began seeing more posts about promising treatments and improving research. She felt encouraged by families posting photos of children meeting milestones at 5 years old, living, even thriving, with a disease that used to take lives before the age of 2. Kelly started to wonder if they should try having another baby. Soon, she was pregnant with March. 

Because of their family history with SMA, Kelly had an amniocentesis test done at 20 weeks which confirmed her baby had SMA-1.  

Kelly said she used her experience of caring for Graham as inspiration to pursue every possible avenue of therapy for March. She found the answer in the online SMA community, where Dr. Richard Finkel’s name appeared as an empathetic caregiver who’d spent decades caring for children with catastrophic neurological diseases.  

“If you’re going to get one man’s opinion, it’s Dr. Finkel’s.  We knew that he was the expert,” Kelly said. 

Finkel had been working at St. Jude for only one year when Kelly reached out to him. 

Kelly said Finkel scheduled a video call where they discussed the latest treatments and their pros and cons. He explained that approved treatments for SMA-1 are not cures but they improve survival and motor function in infants, and the outcomes tended to be better the earlier the child started taking the medicine. Babies with SMA-1 typically have symptoms that begin at birth or in the first 6 months of life and left untreated, the disease progressively worsens over time with further breakdown of neurons (the body’s signal pathways). 

Ultimately, Finkel suggested trying risdiplam, a drug that had been effectively used in infants, and he suggested starting treatment during the prenatal period because emerging research showed it might be effective in utero. 

“We were ready and really wanted the opportunity to try something that could help,” Wes said. Kelly took risdiplam during her third trimester, and March continued to take the drug after she was born. 

The approach seemed to pay off: when March was evaluated at 18 months she had no identifiable features of SMA. From that time she has continued treatment with risdiplam and also received another approved SMA therapy. She is now three years old and still has no symptoms of SMA. She feeds herself, plays with toys and loves tickling her twin big sisters, Pippa and Hogan.

“This has opened up a new era for treatment, so that we can prevent the long-term consequences of these genetic mutations before they even start. It is incredible,” said J. Paul Taylor, MD, PhD, Executive Vice President/Scientific Director and Director of the St. Jude Pediatric Translational Neuroscience Initiative (PTNI).  

Taylor said there were a lot of people at St. Jude involved in coordinating all the logistics for this to happen, including managing the high-risk pregnancy care for the mother and working with the U.S. Food and Drug Administration and the pharmaceutical company to allow the prenatal use of the medicine. St. Jude was able to quickly marshal these resources because of generous donations, Taylor said, that allow the kind of staffing, collaborations and influence that can propel research forward.  “You know, it wouldn't have happened without St. Jude… we could see the impact and value of this, and we could move fast.”

Hope for more Families

The couple was among the first families to be part of the research conducted by the St. Jude Center for Experimental Neurotherapeutics (CENT). CENT, which is led by Finkel, is the clinical research arm of PTNI. 

PTNI was launched in 2018 to improve the understanding and treatment of catastrophic neurological disorders in children. Many of these diseases are driven by a single gene mutation. While scientists are uncovering the molecular roots for these neurological disorders, unlike SMA-1, most still lack any effective treatments. Finkel sees an opportunity to accelerate the development of novel therapies for seriously ill children.

 “St. Jude is well known for its research in cancer, so it had all the infrastructure. It had everything I needed, all the building blocks to be able to use as resources, as I build out our neuroscience program,” Finkel said.

PTNI is a collaborative ecosystem that drives basic research on the underlying causes of catastrophic pediatric neurological diseases, facilitates the rapid clinical development of promising treatments for those diseases and pursues the collaborations and advocacy necessary for those novel therapies to reach patients. 

“One of the things that caught my attention when I was being recruited to come to St. Jude was what Danny Thomas is famous for saying, that ‘no child should die in the dawn of life’,” Finkel said. “To be able to take that view I think is really something very special… particularly when dealing with children with catastrophic diseases, many of whom have no treatment and aren't going to get into the adult years unless we identify a drug, try to develop it and hopefully help them.”

Finkel tapped into that mission to help Wes, Kelly and March.   

Looking back, Wes and Kelly said they’re grateful for their experience at St. Jude.

“We’re starting to see how our journey has helped other people,” Wes said. “It’s like St. Jude has been great at kicking cancer’s butt. If they can start to do for these neurological disorders what they’ve done for cancer, then we’re just at the beginning of some really exciting times and saving a lot more kids’ lives.”