Personalized healthcare is rapidly evolving as a result of advancements in technology, genetics and our growing understanding of the pathophysiology underpinning greater than 7,000 single gene inherited diseases. In the field of pediatric neuromuscular medicine, these rare and often devastating disorders are forging the development and application of personalized healthcare strategies, offering hope for the broader healthcare landscape.
Pediatric neuromuscular diseases include disorders with onset in childhood where the primary area of pathology is in the muscle, neuromuscular junction, peripheral nerve, or neurons in the spinal cord. Most conditions are genetic in etiology with some conditions acquired and primarily immune mediated.
Genetic insights and recent breakthroughs in gene therapy are reshaping the way we understand and treat these disorders, to the extent that significantly improved outcomes have already been achieved. The greater accessibility of comprehensive neuromuscular genetic testing has resulted in earlier identification and precise diagnosis of many of these conditions, allowing for potentially tailored and targeted treatment strategies such as gene therapy.
Spinal muscular atrophy (SMA) is now part of the newborn screening in many states, and Duchenne muscular dystrophy (DMD) may be included on screenings in select states in 2024. With the addition of SMA to the Arizona newborn screening in January 2022, Barrow Neurological Institute at Phoenix Children’s became part of the Newborn Partners Consortium. We have established same-day genetic notification, next-day evaluation and protocols to ensure early treatments.
Changing Gene Expression, Replacing Genes, Building Muscle, Preventing Muscle Destruction and Altering Immunity at Phoenix Children’s
Innovative and novel treatments in pediatric neuromuscular diseases, particularly SMA and DMD, have shown significant promise in recent years, offering new hope to children and their families. The perception of limited treatment and poor prognosis associated with these disorders has changed as the treatment of pediatric neuromuscular disorders has evolved to incorporate multiple approaches.
Gene therapies include modifying, upregulating or replacing genes to address specific mutations. Current examples include Zolgensma, a single intravenous administration of a functional copy of the SMN1 gene; Spinraza, an antisense oligonucleotide (ASO) gene splicing therapy for SMA; various exon skipping therapies for DMD; and pharmacologic oral small molecule therapies allowing stop codon read through and enhancement of protein production in SMA and DMD.
Other treatments – to prevent muscle fibrosis and inflammation, to enhance muscle growth and strength, to improve cardiac or pulmonary function, or to alter immunity to prevent progression – have been adopted or are in clinical trials at Phoenix Children’s.
The Neuromuscular Clinic at Phoenix Children’s, under the auspices of Saunder Bernes, MD, is a nationally recognized center of excellence at the forefront of pediatric neuromuscular care. We have treated more than 18 patients with Zolgensma gene replacement therapy, with the first treatment in July 2019. We have administered over 625 doses of intrathecal antisense oligonucleotide therapy (Spinraza). An oral small molecule that enhances survival motor neuron protein production (Risdiplam) has also been used in over 30 patients including pre-symptomatic newborns. We are treating over 35 Duchenne patients with exon skipping therapy with amenable deletions. Ongoing clinical trials include cell-based mediated therapy, myostatin inhibitors, immune modulating therapy [one of only two U.S. sites completing a trial for childhood chronic inflammatory demyelinating polyneuropathy (CIDP)] and an ongoing phase 2 trial with a neonatal receptor, antibody-lowering monoclonal antibody trial for generalized myasthenia gravis.
Outcomes and Quality
Personalized healthcare goes beyond the initial diagnosis and treatment plans. Monitoring disease progression, therapy responses and adherence to evidence-based guidelines are important components to enable adjustments to treatment strategies as required. Advances in telemedicine and digital health tools make it easier and more accessible for families to interact with their caregivers and ensure optimal care.
Real-time dashboards ensure best practices are implemented by identifying important patient care metrics and informing providers electronically, in advance of their patients’ visit that day, of any missing elements. The dashboards also help identify providers of any potential research studies the patient may be eligible for based on certain selected data. These opportunities can help to inform clinical decisions and ensure standardization of care. Data collected through these dashboards are also valuable for research and our ongoing quality improvement efforts.
Future efforts will focus on the development of home applications for self-entered data to track and monitor treatment responses and complications that link back to the dashboards and allow for timely interventions. As a Cure SMA Regional Treatment Site, PPMD Certified Duchenne Center, designated Muscular Dystrophy Association Clinic and participant in several national registries, we ensure transparency, accountability and best practices to provide the best outcomes to our patients and their families.