Lauren Elman, MD
Lauren Elman, MD, an associate professor of Neurology, has spent part of her career caring for a group of patients with no treatment options. The genetic disease, spinal muscular atrophy (SMA), can strike beginning at birth and robs patients of their ability to walk, eat, and breathe. SMA is the leading genetic cause of death for infants and the second most common autosomal recessive disease—a disease inherited through two mutated genes—occurring in about 1 in 10,000 people. But now, there’s hope in a new treatment option.
The United States Food and Drug Administration (FDA) announced the approval for Spinraza (nusinersen) in December 2016, making it the first-ever FDA-approved therapy for SMA. The clinical trials for the drug showed improved motor function in young patients with the most severe forms of SMA. While there is only limited data on the effectiveness of the drug in adults, the FDA approved its use for all patients who are confirmed to have the gene mutation which causes SMA.
That approval started Elman on her quest to bring the therapy to patients at Penn Medicine.
“As soon as the FDA approved this therapy, our patients were asking for it,” explains Elman. “It took hard work to create an SMA treatment program here for adults, but I’m proud to say that we’ve been up and running since August 2017. We were the first center in Philadelphia to offer treatment to adults and we’re the largest program in the area.”
There are four types of SMA, characterized by the severity of disease symptoms. SMA type 1 is the most common and occurs within the first six months of life. Babies typically have difficulty breathing, sucking, and swallowing. Children with type 1 are unable to sit without support and most only live a few years due to complications with breathing.
SMA type 2 has onset between the age of 7 months and 18 months. Children with SMA type 2 may reach motor milestones such as sitting independently, but few are able to stand or walk unaided. SMA type 3 occurs in older children and teens who learn to stand and walk, but lose the ability later in life. SMA type 4 affects full-grown adults, with onset typically in the second or third decade of life.
Thanks to the new therapy, some children are learning to stand and many are sitting unassisted—abilities unheard of before treatment. Many others maynot experience any further loss or deterioration of skills. For adults, the effect of the drug is less clear with possibilities including improvement in or stabilization of symptoms, with the hope that no additional function will be lost.
“When I learned about SMA in medical school it was untreatable. We were just starting to learn what caused it. Now, there’s a treatment that’s truly remarkable,” Elman said. “Stopping progression in a neurodegenerative disease is a home run. And any improvement—that’s a grand slam. I have some patients who’ve had reflexes return that were gone for years. This just has not happened before in diseases like this. It’s truly astonishing.”
The treatment—which is administered through an injection into the spinal fluid—can be difficult as many patients have complicated anatomy resulting from scoliosis (a curvature of the spine common in SMA patients). Interventional radiology experts ensure the treatment is delivered to the right location. There is also a complicated dosing schedule—four doses are given over a 10-week loading period, with a maintenance dose given every four months thereafter. By developing a multidisciplinary effort between teams in neurology, radiology, and pharmacy, patients are now able to get the treatment they need.
What’s more, there are research initiatives and clinical trials underway, bringing more hope for future breakthroughs. Elman says gene therapy for SMA could be possible since the disease is caused by the deletion or mutation of a single gene, and because a good vector for delivering a replacement gene is available. The vector being used to study gene replacement therapy for patients with SMA is the adeno-associated virus (AVV), which is a vector that has already been successfully used in people.
“Patients have hope where they never had hope before,” Elman said. “It’s the most rewarding thing I have ever been part of.”