A Tale of Two Therapies: One or Both in SMA? The University of Rochester Experience


Practical Considerations in Manufacture and Use of Gene Targeted Therapies

Poster Number: 136


Debra Guntrum, MS, FNP, Lindsay Baker, DPT, Kate Eichnger, PT PhD, Erin Collins, MS, Bo Lee, MD, Emma Ciafaloni, MD


1. University of Rochester Medical Center, 2. University of Rochester, 3. University of Rochester, 4. University of Rochester, 5. University of Rochester, 6. University of Rochester

Objective: To identify the medical and family decision making process in deciding on treatment with nusinersen or gene therapy for pre-symptomatic infants diagnosed with spinal muscular atrophy (SMA) through newborn screening. To identify and discuss how we continue to evaluate these infants post-treatment. To present four cases of infants treated at the University of Rochester with both Zolgensma and nusinersen.
Background: SMA is an autosomal recessive neuromuscular disease characterized by progressive degeneration and loss of spinal cord and brainstem motor neurons that are responsible for muscle contraction. It is caused by homozygous deletions of the survival motor neuron 1 (SMN1) gene. In October 2018, SMA was added to the newborn screen panel in New York State. There are currently two FDA approved treatments for SMA, nusinersen and Zolgensma.
Methods: Retrospective chart review of patients with SMA identified through newborn screen (n=4) and patients who received both Zolgensma and nusinersen (n=2). Parents surveyed by telephone interview as to their reasons for choosing one therapy over the other.
Results: We have seen four infants with SMA identified through newborn screen. One infant has 2 copies of SMN2 and is predicted to develop SMA type 1 and the other 3 have 3 copies of SMN2 and are predicted to develop SMA type 2. One infant had received loading doses of nusinersen as he was born prior to approval of Zolgensma and has since received the gene therapy. The other three have or will be treated with Zolgensma. All four had normal exam and CMAP of ulnar and peroneal nerves.
We have three infants with 2 copies of SMN2(Type 1 SMA) all who have received loading doses of nusinersen, are now on maintenance therapy, and have also received Zolgensma. We continue to evaluate with neurologic exams and standardized outcome measures.
Conclusion: With the FDA approval of two therapies for SMA, we are challenged with helping families to decide on treatment option for their child, how to monitor pre-symptomatic infants, and when to consider adding additional therapy.