Spinal Muscular Atrophy: A Q&A with Dr. Fawn Leigh

Spinal muscular atrophy (SMA) is the leading genetic cause of death for infants. Seattle Children’s neurologist Fawn Leigh talks about the fast-changing landscape of research and treatment that is bringing new hope to patients and their families.

What do you want providers to know about SMA?

Dr. Fawn Leigh, neurologist, Seattle Children’s: Being aware of SMA and spotting it early is very important in getting babies into treatment. It can be seen as early as during the newborn checkup. The most common feature of infants with SMA is hypotonia (low muscle tone). We typically see babies with neck flexor weakness, where they can’t lift their head on their own, and significant head lag when pulling up. There’s an absence of reflexes too. But the main thing is hypotonia; that’s the red flag providers should watch out for.

What if my patient has signs of SMA?

Dr. Leigh: If there’s any concern for hypotonia at all, it’s best to make a referral to Neurology at Seattle Children’s for further evaluation. Providers should note the concern for SMA in their referral so that our triage nurses in Clinical Intake will flag it. We have a pathway to expedite these babies into clinic and can see them rapidly, within one to two weeks. Our Neurology division is very much in support of expedited care and seeing acuity faster when we hear from the pediatrician that there’s a concern.

What’s new in treating SMA?

Dr. Leigh: The field of treatment for SMA is exciting right now. Whereas 10 years ago the parents of a baby with SMA would be told it was fatal and there was no treatment, today we can offer treatment options that improve survival and provide a healthier life for their baby. The newest therapy is a gene therapy called Zolgensma. It was recently approved by the Food and Drug Administration (FDA) at the end of May for children under two years old. Seattle Children’s participated in the clinical trials for Zolgensma, which gave us the ability to rapidly translate our experience to the clinical care setting after FDA approval. We are already treating infants here, with promising results.

What is the future of SMA treatment?

Dr. Leigh: There are still many things we are learning about these new therapies. We want to be able to offer gene therapy to children over two years of age, and clinical trials are investigating safe and effective ways to deliver gene transfer in this older age group. The drug discovery pipeline for SMA is emerging rapidly. We will see more therapies become available in oral form, novel nanoparticles, and/or combination therapies. Clinical trials are in the works, and my hope is that there will be a steady stream of FDA-approved drugs that will become available for clinical implementation.

Any other big news for patients with SMA?

Dr. Leigh: I’m happy to report that the Washington State Board of Health recently voted to add SMA to Washington state’s newborn screening panel, with estimated start of screening in summer 2020. This is a huge win for babies. Earlier treatment equals better outcomes. My goal is to have every newborn with SMA diagnosed as early as possible and to be able to initiate treatment quickly.

What is your outlook on treating SMA?

Dr. Leigh: It’s been a growth experience for me working with SMA. We have so many more options than we did a decade ago, and I believe in another decade we will have significantly fine-tuned our treatment pipeline. The trajectory for SMA will be different from natural history. And this change is very much welcomed.

When I think back to my early years, before treatments became available, having a new baby diagnosed with SMA was devastating. I trained in neurology and observed my attendings diagnose and counsel parents, and I remember when I had to deliver my first infantile SMA diagnosis. It broke my heart. I was telling this young couple their baby had SMA and there was no effective treatment. Now, these FDA-approved treatments have entirely changed the prognosis and survival. There is hope now for potentially curative therapies. I have an entirely different conversation with families today. Now I can say “you have options,” not just one but two therapies, and there are even more clinical trials that are ongoing with potentially helpful treatments in the future.

I’m also realistic. We know little about these new therapies, and we need to closely monitor the children long term. In addition to hope, we always want to give great care and support the kiddos as best we can.

Resources

“Breakthrough gene therapy at Seattle Children’s offers hope for infants with muscular disease,” Seattle Times. May 31, 2019.