Potential treatment in the works for 3 siblings with ultra rare form of SMA
US researchers developing stem cell therapy for disease type marked by seizures
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- U.S. scientists are working to develop a treatment for an ultra-rare form of SMA diagnosed in three siblings in California.
- The teens live with SMA-PME, which is marked by muscle contractions and seizures.
- The family is now raising money to fund the costs of research into a potential stem cell therapy to treat the condition.
Researchers at Cedars-Sinai are working to develop a potential stem cell treatment for three teenage siblings in California with an extremely rare form of spinal muscular atrophy (SMA) for which there are no available therapies targeting the disease’s underlying cause.
The Vehling trio — sisters Emilie, 19, and Maggie Mae, 16, along with brother Brodie, 18 — have SMA associated with progressive myoclonic epilepsy (PME), an inherited neurodegenerative disease marked by muscle contractions, known as myoclonus, and seizures. According to Cedars-Sinai, only 31 people worldwide have been diagnosed with SMA-PME, and the siblings account for three of the five known cases in the U.S.
Now, scientists are on the hunt for a new treatment that would use the siblings’ own cells: A research team led by Michelle Allen-Sharpley, MD, PhD, director of the pediatric neuromuscular program at Cedars-Sinai Guerin Children’s in Los Angeles, is in the early stages of developing a potential therapy that would use a patient’s own stem cells. The treatment would replace acid ceramidase, the enzyme deficient in SMA-PME.
The Vehling family has launched a fundraising campaign to support Allen-Sharpley’s research, aiming to raise $6 million. According to Cedars-Sinai, the family is nearing the $2 million mark, largely through donations from family, friends, and others inspired by their story.
“I feel like this is my calling,” said Allen-Sharpley in a news story from Cedars-Sinai. “The Vehlings came to me looking for hope, in a situation where no specific treatment exists. I want to help them, and every child and family facing this devastating disease.”
For the Vehlings, the first signs that something was wrong seemed relatively harmless. When Emilie was 14, she began dropping silverware and spilling things at the dinner table. At first, her family thought she simply was uncoordinated.
“She would spill her milk at dinner and we’d think, ‘oh, you’re so clumsy,’” recalled her mother, Mollie Vehling.
But the episodes became more frequent and increasingly severe. The family eventually learned that Emilie was experiencing myoclonic seizures — sudden, brief muscle jerks that can be an early sign of SMA-PME. Cheek-swab genetic testing soon revealed that younger siblings Brodie and Maggie Mae also had the disease. The family’s oldest child Lillie, now 21, is the only sibling not diagnosed with the condition.
According to Brodie Vehling, “there have been some very low times.” He added: “This disease has hit me really deep, but I know that the doctors are doing their best to help us.”
Sibling’s rare SMA type caused by different gene mutation
Unlike most cases of SMA, which are caused by mutations in the SMN1 gene, SMA-PME is instead caused by mutations in the ASAH1 gene. These mutations result in a deficiency of acid ceramidase, an enzyme needed to break down certain fatty molecules, called ceramides, inside cells.
The disease is inherited in an autosomal recessive manner, meaning a child must inherit a disease-causing mutation from both parents. Mollie and Derek Vehling did not know they carried a mutation associated with SMA-PME, so the couple was unaware their children were at risk of developing the condition until symptoms emerged during adolescence.
The resulting enzyme deficiency disrupts normal cellular processes and leads to progressive neurological and muscle problems. Symptoms can include muscle weakness, mobility problems, and seizures, as well as cognitive and speech difficulties and hearing loss. Importantly, however, as with any disease, SMA-PME can affect people differently, even within the same family.
Emilie and Brodie experience recurring seizures and have received vagus nerve stimulation devices, which send electrical signals through a nerve in the neck to help control seizures. For Maggie Mae, even everyday sounds can trigger an episode.
“I have to wear earplugs because noises or voice levels can cause my seizures,” Maggie Mae said. “I drop things or fall when I’m walking and my whole body just jerks.”
Family raising funds to support rare disease research – and a treatment
Though not diagnosed herself with this ultra-rare SMA type, watching her siblings navigate activities that most people take for granted has also changed Lillie Vehling’s perspective.
“I’ve had to learn a different way of showing up,” Lillie said. “Things most people treat as background noise—a flight of stairs, a morning workout, the simple act of walking outside, carry a weight for me now and witnessing what my siblings have to endure has made the ordinary feel precious in a way that is hard to articulate.”
For the family, with no treatment currently available that addresses the underlying cause of SMA-PME, care focuses on managing its symptoms.
Allen-Sharpley and her colleagues hope their stem cell-based approach could go a step further by addressing the enzyme deficiency itself. The work, however, remains at an early research stage.
Although each rare disease affects a relatively small number of individuals, collectively, rare diseases impact millions of people worldwide. … Advances made in rare disease research … can generate broader scientific insights that … in turn [accelerate] innovation across medicine.
Joyce So, MD, PhD, chief genomics officer at Cedars-Sinai, noted that while this work specifically targets SMA-PME, “advances made in rare disease research … can generate broader scientific insights that will inform our understanding of [other] more common conditions, which in turn accelerates innovation across medicine.”
“Although each rare disease affects a relatively small number of individuals, collectively, rare diseases impact millions of people worldwide,” So added.
The Vehlings have turned their experience into an effort to accelerate this research. Their fundraising effort has drawn substantial support from the Los Angeles firefighting community, where Derek Vehling worked before retiring. The Widows, Orphans & Disabled Firefighter’s Fund of the Los Angeles Firemen’s Relief Association has donated $750,000 to support SMA-PME research at Cedars-Sinai.
As they help push research forward, the Vehlings are holding onto hope that medical advancements will one day restore their own children’s health.
“Our faith, our family are just so incredibly strong,” Mollie Vehling said. “Derek and I are inspired by our children’s resilience.”
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