Managing Spinal Muscular Atrophy Nancy Kuntz, MD Professor of - - PowerPoint PPT Presentation

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Managing Spinal Muscular Atrophy Nancy Kuntz, MD Professor of - - PowerPoint PPT Presentation

Mar 30, 2024 307 likes •478 views

CME / CE Managing Spinal Muscular Atrophy Nancy Kuntz, MD Professor of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine SMA Spinal Muscular Atrophy A genetic neurodegenerative disorder Mutations in SMN1

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CME / CE

Managing Spinal Muscular Atrophy

Nancy Kuntz, MD Professor of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine

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SMA

Spinal Muscular Atrophy

  • A genetic neurodegenerative disorder
  • Mutations in SMN1 gene leads to reduced SMN protein
  • Reduced SMN protein levels results in a plethora of cellular

events that can lead to neuronal degeneration

  • Multiple systems are affected, requiring a multidisciplinary

approach

  • Treatments are available that target the pathophysiology

Shorrock HK et al. Drugs. 2018; 78: 293-305. Bharucha-Goebel D, Kaufmann P. Curr Neurol Neurosci Rep. 29017;17:91

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Multiple Specialties

Mercuri E et al. Neuromusc Disord. 2018; 28: 103-115. Licensed under: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Survival in Type 1 SMA: Effect of Standard of Care

Oskoui M, et al. Neurol. 2007;69:1931-36. Images provided by Dr. Kuntz.

1995-2006 1980-1994

Death or Ventilation > 16 hr/day Death

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Multiple Disciplines

  • Coordinator
  • Usually a neurologist or pediatric neurologist
  • Neuromuscular care
  • Metabolic bone health
  • Orthopedic care
  • Pulmonology
  • Nutrition/Gastrointestinal care
  • Other (Physiotherapy, Pediatrics, General Practice)
  • Nurses, Nurse Practitioners

Mercuri E et al. Neuromusc Disord. 2018; 28: 103-115.

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SMA Consensus Care Guidelines

  • Stated goals

– Improve quality of life – Reduce disease burden

  • Updated classification system
  • Non-sitters
  • Sitters
  • Walkers
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Neuromuscular

  • Assessment should be performed every 6 months
  • Therapy program will vary depending on person being a non-sitter,

sitter, or walker

  • Stretching
  • Positioning
  • Mobility and exercise
  • Chest physiotherapy

Mercuri E et al. Neuromusc Disord. 2018; 28: 103-115. Images courtesy Dr. Kuntz and CureSMA.

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Orthopedic Management

  • Scoliosis is highly prevalent in SMA type I and II
  • Hypotonic spinal curves and thoracic kyphosis are also common
  • Chest deformity, hip instability, contractures, fragility fractures are also

common

Mercuri E et al. Neuromusc Disord. 2018; 28: 103-115. Licensed under: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Adapted from Talbot et al. Gene Ther. 2017; 24: 529-533. Licensed under: https://creativecommons.org/licenses/by-nc-nd/4.0/.

  • Issues dependent on severity of SMA
  • Non-sitters
  • Swallow test will determine intervention/care
  • Dietician should assess every 3-6 months
  • Sitters
  • Swallow test will determine intervention/care
  • Dietician should assess every 3-6 months
  • Chewing difficulties and fatigue from eating are common in sitters
  • Ambulatory
  • Educate about diet recommended for healthy sedentary person
  • Calcium and Vitamin D
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Rehabilitation Medicine Pulmonology & Respiratory Therapy Neurology/Pediatric Neurology Physical Therapy Genetics/Genetic Counseling Social Work Orthopedics Gastroenterology Anesthesiology Clinic Coordinator

Patients with SMA are optimally treated by a multidisciplinary team at a specialty care center

Nutrition

Multidisciplinary Approach

Clinicians, Nurses, and Other Health Professionals

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Image courtesy CureSMA

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Pathophysiology and Treatment

Parente et al. Ther Adv Neurol Disord. 2018; 11: 1-13. Licensed under: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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  • FDA approved
  • Antisense oligonucleotide drug that modifies pre-mRNA splicing of SMN2 to promote

increased production of full-length SMN protein

  • Intrathecal injections
  • Loading Dose: First three injections, once every two weeks. Fourth injection 30 days after third

injection.

  • Maintenance dose: Once every four months
  • Phase 3 studies with type 1 and type 2 complete showing the drug to be safe and effective

Nusinersen

Image courtesy Dr. Kuntz

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Onasemnogene Abeparvovec

  • Crosses the blood-brain barrier; targets neurons
  • Non-integrating, nonpathogenic
  • Rapid onset of effect
  • Remains stable within the nucleus
  • Rapid, sustained SMN expression

scAAV ITR Continuous Promoter Human SMN Transgene scAAV ITR

Image courtesy Dr. Kuntz

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Risdiplam

  • Under Priority Review by the FDA (announced November 2019. PDUFA date May

24, 2020)

  • SMN2 splicing modifier
  • Numerous clinical trials underway. Preliminary phase 3 data appears promising

but results have yet to be published in a peer-reviewed publication. Two pivotal clinical trials (one involving SMA type 1 and one involving SMA type 2/3)

Image courtesy Wikimedia Commons

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Summary

  • SMA is a genetic neurodegenerative disorder
  • Treatment requires a multidisciplinary approach
  • Treatment dependent on severity
  • Drugs approved, or in development, are designed to stop progression of the
  • disease. While treatments are effective, these children and young adults will still

require extensive care by a number of specialists

  • Since these medicines can dramatically stop progression which means that early

detection (i.e., newborn screening) can have a profound impact on the person’s quality of life (and their families)