Advocacy organization Cure SMA provides insight on the importance of continuing to push for standardized newborn screening and how it can positively impact outcomes in SMA.
September is Newborn Screening Awareness Month, which raises awareness that newborn screening is a public health program designed to identify conditions that affect a child’s long-term health or survival. This month offers an opportunity to talk about the progress we have made in getting spinal muscular atrophy (SMA) added to newborn screening panels and the work still to be done.
Newborn screening for spinal muscular atrophy (SMA) has become an expectation in the United States. The FDA approval of the first disease-modifying therapy for SMA in 2016 provided effective early treatment. This approval opened the path to adding SMA to the federal Recommended Uniform Screening Panel (RUSP) in 2018, making it one of the disorders the Secretary of the US Department of Health and Human Services (HHS) recommends for states to screen as part of their state universal newborn screening programs.
In 2008, the first nomination to consider SMA for newborn screening was denied because there was not an effective treatment for SMA at the time, and no state pilot programs had been initiated. However, in February 2017, a multidisciplinary team led by Cure SMA resubmitted a nomination for SMA, which was accepted for full evidence review. This was supported by an SMA newborn screening pilot program that was initiated in New York State in 2016, in addition to having an FDA-approved treatment. The Condition Review Workgroup completed their review, and in February 2018, the Advisory Committee on Heritable Disorders in Newborns and Children met to deliberate the evidence and voted to recommend adding SMA to the RUSP. The HHS Secretary signed the recommendation in July 2018, officially adding SMA to the RUSP.
In January 2018, just prior to adding SMA to the RUSP, the state of Utah began permanent SMA newborn screening, followed shortly after by Minnesota and later by the state of New York. That same year, pilot SMA newborn screening studies began in Massachusetts, Indiana, and North Carolina.
By the end of 2019, 10 states in the US had implemented permanent screening and 3 additional states began pilot programs. In 2020, 17 new states implemented SMA newborn screening, making it the most successful year to date in implementing newborn screening for SMA. As of June 2021, 38 states are screening for SMA through permanent SMA screening programs and pilot or population screening programs (FIGURE). This means that nearly 85% of all infants born in the US are now screened for SMA. Cure SMA, in partnership with the SMA community in nonscreening states, continues to advocate for and support implementation, with a goal of 90% of US newborns being screened for SMA by the end of 2021.
Shortly after birth, infants are tested for multiple serious disorders that may not present clinically at birth. Early diagnosis facilitates early treatments before harmful effects occur. To screen for diseases, such as SMA, a blood test is performed 24 to 48 hours after birth. If a condition is identified, parents are immediately notified, and follow-up diagnostic testing is conducted. This public health process for early diagnosis provides both medical care teams and families with the ability to seek out resources and treatments before the onset of serious and often irreversible symptoms that could drastically affect a child’s life.
SMA is caused by a mutation in the survival motor neuron gene 1 (SMN1). In a healthy person, this gene produces a protein—called survival motor neuron protein or SMN protein—that is critical to the function of the nerves that control our muscles. Without it, those nerve cells cannot properly function and eventually die, leading to debilitating and often fatal muscle weakness.
The newborn screening assay detects the presence or absence of deletion of the SMN1 gene at exon 7 and does not detect point mutations. Therefore, approximately 3%-5% of infants with SMA will not be detected via newborn screening and will present with symptoms of hypotonia.
Newborn screening is essential to providing early SMN-enhancing treatment and achieving the best possible outcomes for infants born with SMA. Clinical trials of each SMN-enhancing treatment in symptomatic SMA infants younger than 6 months of age have demonstrated significant motor function improvement and survival compared to natural history.1-4 Ongoing clinical trials of infants with SMA treated prior to the development of symptoms have also yielded significantly altered disease outcomes compared to natural history.5,6 Because the loss of motor neurons that impact a baby’s motor function is irreversible with SMA, SMA healthcare providers often say that "time is neurons."
A child with suspected SMA, or presenting as SMA newborn screening positive, requires emergent evaluation by a neuromuscular specialist, ideally within 2-3 days, confirmatory genetic testing, counseling about SMA disease, and discussion of treatment options. If symptomatic and identified to have just one copy of SMN1, further testing via SMN1 gene sequencing is indicated to look for a point mutation.7 Consensus expert opinion recommends offering and efficiently providing treatment for infants with 1-4 copies of SMN2 (often referred to as the SMA “back-up gene”).8
To better understand the impact of SMA newborn screening over time, Cure SMA has established an SMA Newborn Screening Registry. Families with an infant diagnosed with SMA via newborn screening, or prenatally, are encouraged to enter data in Cure SMA’s Newborn Screening Registry.
Families can also consent for their providers to enter data on their behalf. As of August 9, 2021, there are 43 newborns in the Registry. More information is available at www.curesma.org/newborn-screening-for-sma/or www.curesma.org/nbsr.
Families with an infant or child diagnosed with SMA are eligible to receive an Information Packet and Newly Diagnosed Care Package from Cure SMA. We encourage healthcare providers to share the Cure SMA website information with their patient’s families, namely our pages for newly diagnosed families. If you would like to have educational materials in your clinic, including resources that have been translated into multiple languages, please complete the Cure SMA Care Series Publications & Clinic Materials Order Form for Health Care Providers or the Cure SMA Care Series Publications Order Form for Individuals and Families.
Cure SMA’s primary focus is to support care of the highest value to individuals with SMA. In 2018, SMA standard of care guidelines were updated and approved based on consensus, due to limited evidence. With the advent of effective treatments and the implementation of newborn screening, the need for an evidence-based standard of care for people with SMA is needed now more than ever. To create the evidence needed for this, Cure SMA established the Cure SMA Care Center Network and SMA Clinical Data Registry to collect a cross-section of real-world data about SMA care.
As of today, the Cure SMA Care Center Network has 19 sites across the country, representing SMA care for both children and adults. The Network is supported in part by a grant from the Oscar G. and Elsa S. Mayer Family Foundation and an endowment from Bill and Susan Orr and the Tyler William Orr Memorial Fund.
Centers, a collection of neuromuscular clinics with clinical expertise, provide multidisciplinary care for people with SMA. A large component of the Care Center Network is the utilization of the SMA Clinical Data Registry. Clinicians and patients with SMA and their families are focused on speeding insight and understandings of the disease. To move quicker than ever before, the registry is designed to automate the electronic transfer of consented patients' medical record data directly from the EMR to the Cure SMA Clinical Data Registry platform. This reduces the burden for clinicians and further speeds the ability to see insights in live time to assist with changing outcomes and standards of care. Currently, there are 600 patients in the registry with patients from 38 states. This clinical information is real-world evidence that will be used to guide the best care, develop insights into therapeutic interventions, and create evidence-based standards of care for SMA.
The growth of the Cure SMA Care Center Network and SMA Clinical Data Registry will also be supported by Cure SMA’s recently launched Real-World Evidence Collaboration. This Collaboration will deliver an expanded and validated clinical dataset to be used in the development of the updated standards of care on diagnosis, SMA treatment considerations, and mental and emotional health, as well as adding 10 sites to join the Cure SMA Care Center Network.