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Physicians' Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Physicians' Education Resource®, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Physicians’ Education Resource®, LLC, is approved by the California Board of Registered Nursing, Provider #16669, for 1.5 Contact Hours.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from Biogen.

Provider and Caregiver Connection™: Living with Spinal Muscular Atrophy (SMA): Day to Day Patient Care

Release Date: July 31, 2019
Expiration Date: July 31, 2020
Media: Internet - based

Activity Overview

Spinal muscular atrophy (SMA) is a genetic disorder of the spinal motor neuron, with the majority of cases (95%) due to a mutation or deficiency in the SMN1 (survival motor neuron) gene on chromosome 5q13. This type of SMA occurs in 1 out of 11,000 births and is the primary genetic cause of death in infants. Spinal muscular atrophy is classified into 4 phenotypic groups based on age of onset and motor function; the earlier the age of onset, the greater the impact on motor function. Symptoms primarily involve the voluntary muscles, with those most affected closer to the central portion of the body, such as the shoulders, hips, thighs, and upper back. Complications can occur in which breathing and swallowing functionality is affected. Currently, there is no cure for SMA. Clinical management is primarily supportive care led by a pediatrician or neurologist using a vast array of healthcare disciplines, including physical therapists, nurses, rehabilitation specialists, speech and occupational therapists, pulmonologists, orthopedists, and nutritionists. Early diagnosis is imperative. Initiating care early in the course of disease may help to slow progression and loss of function.

This educational activity begins with a mother and caregiver’s story of her 2 daughters with different forms of SMA—from diagnosis and enrollment in clinical trials to an ongoing journey of challenges and successes. Two expert faculty then build on this caregiver perspective to discuss the pathophysiology and genetics involved in SMA, and how these translated into new treatments that can offer improved quality of life and hope for the future. Faculty conclude with strategies for multidisciplinary collaboration to optimize care of patients with SMA.

Benefits of Participating

  • Gain an understanding of SMA through a caregiver’s narrative
  • Recognize the different clinical phenotypes of SMA and the role of molecular genetic testing in diagnosis
  • Learn the impact of antisense oligonucleotides and gene therapy on patient care
  • Review multidisciplinary strategies for individualized disease management

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Biogen.

Instructions for This Activity and Receiving Credit

  • You will need to log in to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review video files/content until you finish the presentation.
  • At the end of the activity, educational content/video files will be available for your reference.
  • In order to receive a CME/CE certificate, you must complete the activity.
  • Complete the Posttest and pass with a score of 70% or higher, complete the Evaluation, and then click on “Request for Credit.” You may immediately download a CME/CE certificate upon completion of these steps.

Target Audience

This activity is intended for community pediatricians and neurologists, as well as physician assistants, nurse practitioners, primary care physicians, and nurses, involved in the diagnosis, treatment, and management of patients with SMA. This activity will also provide education to a broad multidisciplinary team, who are also invited to participate.

Learning Objectives

Upon successful completion of this educational activity, you should be better prepared to:

  • Recognize therapeutic targets in SMA and the mechanisms of action of the various pharmacologic agents
  • Identify the clinical signs of SMA and integrate diagnostic testing along with the pathophysiology to better understand the disease and to initiate patient management
  • Utilize knowledge of the adverse reactions and toxicities of SMA therapeutic options
  • Apply patient perspectives to clinical practice, facilitating informed decision-making

Faculty, Staff, and Planners’ Disclosures


John Brandsema
John Brandsema, MD
Neuromuscular Section Head and Neuromuscular Education Director
Children’s Hospital of Philadelphia
Assistant Professor of Clinical Neurology
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA

Disclosures: Grant/Research Support: Biogen, AveXis, PTC Therapeutics, Sarepta, Alexion, Cytokinetics, Pfizer, FibroGen; Consultant: Biogen, AveXis, Cytokinetics; Speakers Bureau: Biogen.

Claudia A. Chiriboga
Claudia A. Chiriboga, MD, MPH, FAAN
Professor of Neurology and Pediatrics
Division of Pediatric Neurology, Department of Neurology
Columbia University Medical Center
Director, Pediatric MDA Care Clinic
Pediatric Neuromuscular Division
New York, NY

Disclosures: Grant/Research Support: Roche, AveXis, Biogen; Consultant: Genentech, Roche, AveXis; Speakers Bureau: Biogen Educational Speaker.

Gina Cannady (Caregiver Interviewee)

Disclosures: Biogen Marketing Campaign for Spinraza®

The staff of Physicians' Education Resource®, LLC (PER®), have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME/CE activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME/CE activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.

Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME/CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME/CE activity is for continuing medical and nursing education purposes only and is not meant to substitute for the independent clinical judgment of a physician or nurse relative to diagnostic or treatment options for a specific patient’s medical condition.

The opinions expressed in the content are solely those of the individual faculty members, and do not reflect those of PER® or any of the companies that provided commercial support for this program.

PER Pulse Recaps

1 of 3

PER Pulse™ Recap: Provider and Caregiver Connection™: Living with Spinal Muscular Atrophy (SMA): Day to Day Patient Care

The online continuing medical education activity Provider and Caregiver Connection™: Living with Spinal Muscular Atrophy (SMA): Day to Day Patient Care features an engaging patient–provider discussion, with insights from a caregiver of 2 children with SMA who talks about their diagnosis, enrollment in clinical trials, continued treatment and lifestyle management. John Brandsema, MD, and Claudia Chiriboga, MD, MPH, FAAN, builds on the caregiver’s perspective by describing the early signs of SMA, genetic testing for an accurate diagnosis, and clinical management of SMA. Faculty next discuss therapeutic targets of new and emerging treatments for SMA and the multidisciplinary care team role in individualizing patient care to optimize outcome and quality of life.

This first of 3 PER Pulse™ Recaps will focus on early signs of SMA, phenotypes, and genetic testing, as explored in Provider and Caregiver Connection™: Living with Spinal Muscular Atrophy (SMA): Day to Day Patient Care.

SMA is a genetic disorder of the spinal motor neuron in which the SMN1 gene, located on chromosome 5q13, is missing or deficient. SMA is the most common inherited cause of infant mortality, with an incidence of approximately 1 in 10,000 births in the United States. The SMN1 gene transcribes survival motor neuron (SMN) protein, which is needed for most functions, and neurons are very sensitive to its deficiency.

SMA is classified into 4 phenotypic groups based on age of onset and motor function.1 The earlier the age of onset, the greater the impact on motor function:

The earliest clinical feature of type I SMA is hypotonia, with decreased mobility of the legs and loss of reflexes. Subsequently, there will be delayed motor milestones and difficulty swallowing. Fatigue may also be present and cause an inability to maintain nutrition. Respiration insufficiency and aspiration may not be immediately apparent.

The American College of Obstetricians and Gynecologists recommends carrier screening for women of all ethnicities and the partners of those found to be carriers.2 In 2018, SMA was added to the Recommended Uniform Screening Panel for newborns in the United States, and a growing list of states routinely screen newborns.3,4.

For diagnosis or screening follow-up, molecular genetic testing is done to confirm homozygous deletion of both SMN1 copies. The number of copies may also be determined. Most people with SMA, especially with the most severe forms, have 2 or 3 copies, but up to 4 and even 6 have been found. The SMN2 genes make SMN protein at about 10% the efficiency of an SMN1 gene, so more copies commonly result in milder phenotypes. However, this is not absolute as Dr Chiriboga, a professor of neurology and pediatrics at Columbia University Medical Center in New York, New York, describes: “There are patients who have more copies of SMN2 but still present with that early-onset phenotype of symptoms before 6 months in a classical type I, and there [are] also patients who only have a couple of copies of SMN2 but are ambulatory well into childhood.”

Key Points

  • SMA is a genetic disorder resulting from mutation or deficiency of the SMN1 gene.
  • SMA is classified into phenotypes I to IV based on age of onset and motor function; type I presents earliest, with the most severity and shortest life span.
  • Newborn and carrier screening may allow for earlier diagnosis with confirmatory molecular genetic testing.


  1. Jha NN, Kim JK, Monani UR. Motor neuron biology and disease: a current perspective on infantile-onset spinal muscular atrophy. Future Neurol. 2018;13(3):161-172. doi: 10.2217/fnl-2018-0008.
  2. ACOG recommends offering additional carrier screening to all women, regardless of ethnicity or family history [news release]. Washington, DC: The American College of Obstetricians and Gynecologists; February 27, 2017. Accessed August 20, 2019.
  3. Lunxer L. SMA newborn screening expands as more states enact mandatory testing. SMA News Today website. Published March 26, 2019. Accessed August 20, 2019.
  4. Conditions screened by state. Baby’s First Test website. Accessed August 20, 2019.

2 of 3

PER Pulse™ Recap: Provider and Caregiver Connection™: Living with Spinal Muscular Atrophy (SMA): Day to Day Patient Care

As a follow-up to the online continuing medical education activity Provider and Caregiver Connection™: Living with Spinal Muscular Atrophy (SMA): Day to Day Patient Care, this second of 3 PER Pulse™ Recaps will focus on new and emerging treatments for SMA.

Most of the research for treatment of SMA has focused on correcting the deficiency of SMN through genetic means. The approaches that have been considered involve increasing the inclusion of exon 7 in SMN2 copies, enhancing the expression of SMN2, stabilizing the SMN protein, or replacing the missing or mutated SMN1 gene. Neuroprotective drugs have also been considered to improve motor neuron survival.1

Nusinersen, an antisense oligonucleotide, modulates SMN2 splicing to induce the inclusion of exon 7 retention in SMN2, thereby increasing SMN protein levels. The phase III pivotal randomized, double-blind, sham-controlled ENDEAR trial evaluated symptomatic infants with SMA type I onset after age 3 months. A significantly higher percentage of infants receiving nusinersen had increased motor-milestone response than the controls (21 of 51 or 41% vs 0 of 27 or 0%), which prompted early termination of the study. Final analysis showed not only a significantly higher percentage of patients who received nusinersen with motor-milestone response compared with controls but also greater event-free survival. Furthermore, infants with a shorter duration of disease at screening were more likely to benefit from nusinersen than those with longer duration, suggesting that treatment should be initiated as early as possible.2

Onasemnogene abeparvovec-xioi is a gene therapy given as a single intravenous dose that delivers a copy of SMN in a self-complementary adeno-associated viral serotype 9 to induce SMN expression. Fifteen infants with SMA type I whose mean age at symptom onset ranged from 0 to 3 months were evaluated within high- or low-dose cohorts. As of the data cut-off date, all patients had reached at least 20 months of age. Major milestones— unassisted sitting for up to 30 seconds, head control, and ability to speak— were achieved in the higher-dose cohort (11 of 12 patients), which had never been attained in historical cohorts.3

In addition to these 2 approved treatments for SMA, an oral agent, risdiplam, is being evaluated in pivotal trials of symptomatic infants with SMA type I and children and young adults (2-25 years) with type II or III. Early safety and efficacy data are promising.4,5 An additional approach being investigated involves stabilizing the motor neuron by either activating the troponin aspect of muscle function or inhibiting myostatin.

Key Points

  • New and emerging treatments for SMA correct the deficiency of SMN or stabilize the motor neuron.
  • Nusinersen is an SMN2-directed antisense oligonucleotide indicated for the treatment of SMA in pediatric and adult patients.
  • Onasemnogene abeparvovec-xioi is an adeno-associated vector-based gene therapy indicated for the treatment of patients <2 years of age with SMA with biallelic mutations in the SMN1 gene.


  1. Scoto M, Finkel RS, Mercuri E, Muntoni F. Therapeutic approaches for spinal muscular atrophy (SMA). Gene Ther. 2017;24(9):514-519. doi: 10.1038/gt.2017.45.
  2. Finkel RS, Mercuri E, Darras BT, et al; ENDEAR Study Group. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Eng J Med. 2017;377(18):1723-1732. doi: 10.1056/NEJMoa1702752.
  3. Mendell JR, Al-Zaidy S, Shell R, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med. 2017;377(18):1713-1722. doi: 10.1056/NEJMoa1706198.
  4. Baranello G, Servais L, Day JW, et al. FIREFISH part 1: 1-year results on motor function in babies with type 1 SMA. Neurology. 2019;92(suppl 15). Accessed August 20, 2019.
  5. Servais L, Baranello G, Day JW, et al. FIREFISH part 1: survival, ventilation and swallowing ability in babies with type 1 SMA receiving risdiplam (RG7916). Neurology. 2019;92(suppl 15). Accessed August 20, 2019.

3 of 3

PER Pulse™ Recap: Provider and Caregiver Connection™: Living with Spinal Muscular Atrophy (SMA): Day to Day Patient Care

As a follow-up to the online continuing medical education activity Provider and Caregiver Connection™: Living with Spinal Muscular Atrophy (SMA): Day to Day Patient Care, this third of 3 PER Pulse™ Recaps will focus on management and treatment monitoring in patients with SMA.

The lifelong management of SMA requires individualized care from various specialists that will change as children or adults living with SMA grow and develop or age. A key aspect of optimizing care is the communication between multidisciplinary team members, neurologists, physical and occupational therapists, orthopedists, pulmonologists, gastrointestinal physicians, pediatricians, primary care providers, and other health professionals. This range of services necessitates coordination of care that may also include mental health assessments to ensure that individuals living with SMA can navigate the stressful transitions of life.

Although SMA now has 2 encouraging treatments, John Brandsema, MD, neuromuscular section head and neuromuscular education director at Children’s Hospital of Philadelphia in Pennsylvania, cautions: “It’s very important to keep the message out there for the patients that none of these things are a cure for SMA. They still have SMA as a disease, and even in the best outcomes in the trials, there [are] still manifestations of the disease that are seen in the patients, in terms of having functional impairments and needing to be monitored over time, let alone the long-term monitoring of the safety aspects of the treatments that we really don’t understand yet.”

Warnings and precautions for nusinersen include thrombocytopenia and coagulation abnormalities. Blood and spot urine protein testing is required at baseline, prior to each dose, and as clinically needed.1 For onasemnogene abeparvovec-xioi, acute serious liver injury and elevated aminotransferases can occur, as can thrombocytopenia and elevated troponin I. Liver function should be assessed prior to infusion and monitored for at least 3 months afterward.2

With availability of these new therapies, it becomes even more critical to understand the evolution of the disease and determine over time what or if additional surveillance may be required. Patients should be evaluated twice a year if they’re stable and more often if not. Follow-up is lifelong, even with a onetime treatment of onasemnogene abeparvovec-xioi.

As part of the follow-up, functional scales assess the affect of treatment over time, but it is important to put them in context of each patient’s quality of life. Having less fatigue at the end of the day is key. As Dr Chiriboga emphasizes: “Having mobility that allows you to go to school and use a keyboard or be employed or being able just to negotiate your joystick for your chair is very important.”

Key Points

  • Communication and coordination of care among a range of specialists will optimize care of patients living with SMA.
  • Lifelong monitoring of patients with SMA is essential to optimize changing needs in care, treatment effects, and functional status.
  • Functional assessments should be placed in context of the individual impact on quality of life.


  1. Spinraza (nusinersen) injection [prescribing information]. Cambridge, MA: Biogen; 2019. Accessed August 21, 2019.
  2. Zolgensma (onasemnogene abeparvovec-xioi) [prescribing information]. Bannockburn, IL: AveXis, Inc; 2019. Accessed August 21, 2019.

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