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Noteworthy Professional News

Noteworthy Professional News

Fortney, Christine A. PhD, RN

Editor(s): Eklund, Wakako DNP, NNP-BC, Section Editors; Smith, Heather E. PhD, RN, NNP-BC, CNS, Section Editors

Author Information
doi: 10.1097/ANC.0000000000000783
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CONFRONTING SMA HEAD-ON: MEET THE CAMBONIS

On June 5, 2015, Marybeth and Chris Camboni received devastating news that their 4-month old daughter, Jacqueline (Jackie), had type 1 spinal muscular atrophy (SMA), a neuromuscular disease that causes significant morbidity in the neonate and is a leading hereditary cause of infant mortality.1 A rare disease, SMA is caused by the loss of lower motor neurons in the spinal cord that are critical to the function of nerves that control the muscles. As nerve cells die, they take with them the person's ability to walk, eat, and even breathe—similar to amyotrophic lateral sclerosis in adults. While voluntary muscle movement is affected, the brain and other involuntary processes are not. SMA affects both genders, as well as all races and ethnicities. Four types of SMA have been identified (types 1-4). Historically, SMA has been a life-limiting disorder, with 95% of those with the most severe and common form (type 1) dying or becoming permanently ventilated by 2 years of age.1–4

But, 5 years later, the Camboni family is celebrating recent progress that allows for earlier identification and treatment of SMA and preparing for Jackie to start kindergarten! Amazing accomplishments that will no doubt change the face of this devastating disease. Yet, there is still more work to be done to ensure that all infants affected with SMA are identified and able to receive treatment.

The incidence of SMA is approximately 1 in 11,000 live births and about 1 in every 50 Americans is a carrier of the disease.4 The Cambonis have 2 older children who are not affected, and no one in either of their extended families had ever been diagnosed with a genetic disease. Marybeth and Chris were shocked to learn that they both are SMA carriers. Because the disease is autosomal recessive, each parent has one normal copy and one mutant copy. With every pregnancy, there is a 25% chance that the child will inherit both copies of the mutant gene and be affected with SMA. The American College of Obstetricians and Gynecologists recommends that comprehensive carrier screening information should be offered to every pregnant woman but, ideally, should occur prior to pregnancy to allow time for decision making.5

SMA was first discovered in 1890 by Drs Werdnig and Hoffman,1 but in 2015, when Jackie was diagnosed, there was STILL no Food and Drug Administration (FDA)–approved treatment available and affected infants were offered supportive care. There were also no recommendations for carrier testing, and SMA had not been added to the newborn screening in any state because of its incurable status. But 2 clinical trials were testing nusinersen (Spinraza) and onasemnogene abeparvovec (Zolgensma). These therapies, limited to children with type 1 disease, who were 6 months or younger, work on different underlying causes of SMA. Zolgensma, a gene therapy, infuses a healthy copy of the SMN1 gene to restore cell function of the motor neurons, whereas Spinraza is given to boost the SMN2 gene to produce functional SMN protein that is needed to maintain motor function.6

As fate would have it, Marybeth was working at Nationwide Children's Hospital at the time of Jackie's diagnosis and was quickly referred to the now completed SMART clinical trial that was testing Zolgensma, developed there by researchers. Just 11 days after diagnosis, Jackie received the infusion. Fifteen babies were enrolled in the SMART trial, and families came from all over the world to participate.

On December 23, 2016, Spinraza become the first FDA-approved treatment of SMA.7 Spinraza, delivered as a spinal infusion every 4 months for life, costs more than $200,000 per infusion.

On August 3, 2017, Jackie became the first human to receive a combination of Zolgensma and Spinraza that would target both types of affected cells, the recommended therapy. Doctors thought she might be able to stand but only with braces. In late 2017, Jackie stood WITHOUT braces. Zolgensma was approved by the FDA on May 24, 2019.8 At $2.1 million, it became the world's most expensive drug therapy and available for children 2 years and younger with any type of SMA. The positive results are undeniable. Jackie is now considered to have strong type 2/weak type 3 SMA. She can speak, eat, sit, push her manual wheelchair, breathe independently, and walk in a gait trainer. Jackie is a feisty go-getter who does not see herself as being different from anyone else. She is also a trailblazer. It is anticipated that she will continue to improve and that one day she could even walk on her own.

However, to be treated for SMA, a newborn must first be identified. In the summer of 2018, Alex Azar, Secretary of the US Department of Health and Human Services, approved a recommendation that states should test all newborns for SMA.9 While the decision rests with each state regarding adding the test to its newborn screening panel, since this federal recommendation, 18 states have started screening newborns either permanently or through pilot testing.9

In Ohio, where the Cambonis live, the state is currently piloting SMA testing. Following the approval of a viable treatment option in December 2016, Marybeth contacted her Ohio State Representative Kristin Boggs (D). Enough support was generated around SMA and testing that House Bill 397 was drafted. In December 2017, the Cambonis, joined by a mother who lost her son to SMA in 2012 and a physician, gave testimony at the Ohio Statehouse in support of the bill (Figure 1). The bill did not leave the House of Representatives though because it was learned that the Ohio Department of Health Newborn Screening Advisory Panel could add SMA to the battery of tests on the newborn screen by vote, which they did almost unanimously on February 23, 2018. It took several months for the SMA test to be added, but all newborns born in Ohio in 2019 were screened. At the Ohio Newborn Screening Meeting in March 2020, it was announced that in the first year of testing, 8 infants were identified with SMA, 2 with type 1 and 6 with types 2 to 4 (M. Camboni, BS, personal communication, June 15, 2020), 8 lives that may potentially be altered through early identification and treatment. As the years multiply, so will the numbers of children whose lives can be saved and/or significantly improved.

FIGURE 1
FIGURE 1:
Camboni family newborn screening testimony at Ohio Statehouse. From Marybeth and Christopher Camboni, who have given permission to use the photographs provided of themselves and their children for publication. This figure and individual images within are © Marybeth and Christopher Camboni. Permission is required for reuse.

This is great progress, but current indications are that infants who are diagnosed with SMA must be identified and treated before 2 years of age. The cost of treatment can be prohibitive for families, especially for those without insurance, those whose insurance will not authorize payment for the expensive treatment, or those who live outside of the United States and must pay out-of-pocket. Jackie does not currently qualify for Medicaid or the Children with Medical Handicaps Program in Ohio and has been on the Medicaid waitlist since 2015. The Cambonis feel lucky that their insurance company agreed to cover costs above their deductible for her ongoing treatments, which run about $750,000 per year. Some families ultimately choose to take lower-paying jobs or to make their child a ward of the state so that they can qualify for Medicaid. These are hard decisions that families unfortunately have to make in the midst of caring for their ill child. It is also unclear how treatment costs may ultimately affect decisions regarding the inclusion of SMA testing on state newborn screening panels but is certainly an ethical consideration for continued discussion.

As is true with many childhood diseases, new scientific advances and treatments come about through passion and advocacy. As healthcare providers, it is crucial for us to recognize and acknowledge the full spectrum of issues families may encounter when their child is diagnosed with any potentially life-threatening or life-limiting illness. In the neonatal intensive care unit, education and support of the family are critical as they begin to receive and navigate crucial information and make decisions. We can also join with families to advocate for improvements in care and treatment delivery, as well as for policies and legislation that ensure children diagnosed with SMA have access to lifesaving therapies.

Marybeth and Chris Camboni set forth to bring about process changes that they felt might help other families. They know all too well that with SMA, the earlier the diagnosis is made, the better the chance to obtain treatment, and the longer survival may ultimately be. It is unclear how long Jackie may live. But she has exceeded initial expectations. And, she is achieving milestones, such as starting school. Furthermore, new treatments of SMA continue to evolve. Oral risdiplam was granted priority review by the FDA in November 2019, with an approval decision expected in August 2020.10 Jackie's parents have hope that she, and other children diagnosed with SMA, will continue to defy the odds. While not all families have the ability to testify at the Statehouse, each family does have their own strength and passion that can be leveraged to support their child. We can help them through continued education and advocacy. These remarkable children and their families are counting on it.

References

1. Markowitz JA, Tinkle MB, Fischbeck KH. Spinal muscular atrophy in the neonate. JOGNN. 2004;33(1):12–20.
2. Anderton RS, Mastaglia FL. Advances and challenges in developing a therapy for spinal muscular atrophy. Expert Rev Neurother. 2015;15(8):895–908.
3. National Organization for Rare Disorders (NORD). Spinal muscular atrophy. https://rarediseases.org/rare-diseases/spinal-muscular-atrophy. Accessed June 17, 2020.
4. CureSMA. About SMA. https://curesma.org/about-sma/#. Accessed June 17, 2020.
5. The American College of Obstetricians and Gynecologists. Committee opinion, Carrier screening for genetic conditions, number 691, March 2017. https://www.acog.org/-/media/project/acog/acogorg/clinical/files/committee-opinion/articles/2017/03/carrier-screening-for-genetic-conditions.pdf. Accessed June 15, 2020.
6. Pearson SD, Thokala P, Stevenson M, Rind D. The effectiveness and value of treatments for spinal muscular atrophy: a summary from the Institute for Clinical and Economic Review's New England Comparative Effectiveness Public Advisory Council. J Manag Care Spec Pharm. 2019;25(12):1300–1306.
7. US Food and Drug Administration. FDA approves first drug for spinal muscular atrophy. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-spinal-muscular-atrophy. Published 2016. Accessed June 17, 2020.
8. US Food and Drug Administration. FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality. https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease. Published 2019. Accessed June 12, 2020.
9. American Legislative Exchange Council. Many states now screening newborns for spinal muscular atrophy; others considering action in 2020. https://www.alec.org/article/many-states-now-screening-newborns-for-spinal-muscular-atrophy-others-considering-action-in-2020. Published 2020. Accessed June 5, 2020.
10. Roche. Roche provides regulatory update on risdiplam for the treatment of spinal muscular atrophy (SMA). https://www.roche.com/media/releases/med-cor-2020-04-07.htm. Published 2020. Accessed June 17, 2020.
© 2020 by the National Association of Neonatal Nurses.