scholarly journals Ethical Perspectives on Treatment Options with Spinal Muscular Atrophy Patients

2022 ◽  
Author(s):  
Crystal J. J. Yeo ◽  
Zachary Simmons ◽  
Darryl C. De Vivo ◽  
Basil T. Darras
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Treatment Options ◽  
Ethical Perspectives

scholarly journals Massachusetts’ Findings from Statewide Newborn Screening for Spinal Muscular Atrophy

2021 ◽  
Vol 7 (2) ◽  
pp. 26
Author(s):  
Jaime E. Hale ◽  
Basil T. Darras ◽  
Kathryn J. Swoboda ◽  
Elicia Estrella ◽  
Jin Yun Helen Chen ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Newborn Screening ◽  
New England ◽  
Screening Program ◽  
Muscular Atrophy ◽  
Treatment Options ◽  
Newborn Screening Program ◽  
Treatment Protocols ◽  
Screening Algorithm ◽  
New Treatment

Massachusetts began newborn screening (NBS) for Spinal Muscular Atrophy (SMA) following the availability of new treatment options. The New England Newborn Screening Program developed, validated, and implemented a screening algorithm for the detection of SMA-affected infants who show absent SMN1 Exon 7 by Real-Time™ quantitative PCR (qPCR). We screened 179,467 neonates and identified 9 SMA-affected infants, all of whom were referred to a specialist by day of life 6 (average and median 4 days of life). Another ten SMN1 hybrids were observed but never referred. The nine referred infants who were confirmed to have SMA were entered into treatment protocols. Early data show that some SMA-affected children have remained asymptomatic and are meeting developmental milestones and some have mild to moderate delays. The Massachusetts experience demonstrates that SMA NBS is feasible, can be implemented on a population basis, and helps engage infants for early treatment to maximize benefit.

scholarly journals Muscle overexpression of Klf15 via an AAV8-Spc5-12 construct does not provide benefits in spinal muscular atrophy mice

Gene Therapy ◽  
2020 ◽  
Vol 27 (10-11) ◽  
pp. 505-515
Author(s):  
Nina Ahlskog ◽  
Daniel Hayler ◽  
Anja Krueger ◽  
Sabrina Kubinski ◽  
Peter Claus ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Treatment Options ◽  
Survival Motor Neuron ◽  
Significant Activity ◽  
Dependent Manner ◽  
Patient Response ◽  
High Gene Expression ◽  
Virus Serotype ◽  
High Gene

AbstractSpinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the survival motor neuron (SMN) gene. While there are currently two approved gene-based therapies for SMA, availability, high cost, and differences in patient response indicate that alternative treatment options are needed. Optimal therapeutic strategies will likely be a combination of SMN-dependent and -independent treatments aimed at alleviating symptoms in the central nervous system and peripheral muscles. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates key metabolic and ergogenic pathways in muscle. We have recently reported significant downregulation of Klf15 in muscle of presymptomatic SMA mice. Importantly, perinatal upregulation of Klf15 via transgenic and pharmacological methods resulted in improved disease phenotypes in SMA mice, including weight and survival. In the current study, we designed an adeno-associated virus serotype 8 (AAV8) vector to overexpress a codon-optimized Klf15 cDNA under the muscle-specific Spc5-12 promoter (AAV8-Klf15). Administration of AAV8-Klf15 to severe Taiwanese Smn−/−;SMN2 or intermediate Smn2B/− SMA mice significantly increased Klf15 expression in muscle. We also observed significant activity of the AAV8-Klf15 vector in liver and heart. AAV8-mediated Klf15 overexpression moderately improved survival in the Smn2B/− model but not in the Taiwanese mice. An inability to specifically induce Klf15 expression at physiological levels in a time- and tissue-dependent manner may have contributed to this limited efficacy. Thus, our work demonstrates that an AAV8-Spc5-12 vector induces high gene expression as early as P2 in several tissues including muscle, heart, and liver, but highlights the challenges of achieving meaningful vector-mediated transgene expression of Klf15.

scholarly journals Current understanding of and emerging treatment options for spinal muscular atrophy with respiratory distress type 1 (SMARD1)

2020 ◽  
Vol 77 (17) ◽  
pp. 3351-3367 ◽  
Author(s):  
Martina G. L. Perego ◽  
Noemi Galli ◽  
Monica Nizzardo ◽  
Alessandra Govoni ◽  
Michela Taiana ◽  
...  
Keyword(s):  
Respiratory Distress ◽  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Treatment Options ◽  
Current Understanding

Emerging treatment options for spinal muscular atrophy

2009 ◽  
Vol 11 (2) ◽  
pp. 90-101 ◽  
Author(s):  
Barrington G. Burnett ◽  
Thomas O. Crawford ◽  
Charlotte J. Sumner
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Treatment Options

scholarly journals Parents’ Experiences of Information and Decision Making in the Care of Their Child With Severe Spinal Muscular Atrophy: A Population Survey

2019 ◽  
Vol 34 (4) ◽  
pp. 210-215 ◽  
Author(s):  
Kim Beernaert ◽  
Malin Lövgren ◽  
Jørgen Jeppesen ◽  
Ulla Werlauff ◽  
Jes Rahbek ◽  
...  
Keyword(s):  
Health Care ◽  
Decision Making ◽  
Spinal Muscular Atrophy ◽  
Population Survey ◽  
Muscular Atrophy ◽  
Treatment Options ◽  
Care Staff ◽  
Health Care Staff ◽  
Bereaved Parents ◽  
Advance Care

Objective: This study aims to assess the experiences and wishes of parents of children with severe spinal muscular atrophy regarding information and decision-making throughout the course of the illness. Study Design: A full population survey, conducted in 2015, among parents of children with severe spinal muscular atrophy who were born in Denmark between January 1, 2003, and December 31, 2013. We used a study-specific questionnaire with items about experiences and wishes concerning the provision of information about diagnosis, treatment, and end-of-life care. Results: Among the 47 parents that were identified, 34 parents of 21 children participated. Eleven of them were nonbereaved and 23 were bereaved parents. All parents stated that health care staff did not take any decisions without informing them. A proportion of parents indicated that they were not informed about what spinal muscular atrophy entails (32%), possible treatment options (18%), or the fact that their child would have a short life (26%) or that death was imminent (57%). Most of the bereaved parents who had wishes concerning how and where their child would pass away had their wishes fulfilled. Conclusions: The study showed that health care staff did not take treatment decisions without parents being informed. However, there is room for improvement concerning information about what spinal muscular atrophy entails, treatment options, and prognosis. Possibilities of palliative care and advance care planning should be investigated for these parents, their child, and health care staff.

scholarly journals Muscle overexpression of Klf15 via an AAV8-Spc5-12 construct does not provide benefits in spinal muscular atrophy mice

2019 ◽  
Author(s):  
Nina Ahlskog ◽  
Daniel Hayler ◽  
Anja Krueger ◽  
Sabrina Kubinski ◽  
Peter Claus ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Treatment Options ◽  
Survival Motor Neuron ◽  
Significant Activity ◽  
Dependent Manner ◽  
Patient Response ◽  
High Gene Expression ◽  
Virus Serotype ◽  
High Gene

ABSTRACTSpinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the survival motor neuron (SMN) gene. While there are currently two approved gene-based therapies for SMA, availability, high cost, and differences in patient response indicate that alternative treatment options are needed. Optimal therapeutic strategies will likely be a combination of SMN-dependent and -independent treatments aimed at alleviating symptoms in the central nervous system and peripheral muscles. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates key metabolic and ergogenic pathways in muscle. We have recently reported significant downregulation of Klf15 in muscle of pre-symptomatic SMA mice. Importantly, perinatal upregulation of Klf15 via transgenic and pharmacological methods resulted in improved disease phenotypes in SMA mice, including weight and survival. In the current study, we designed an adeno-associated virus serotype 8 (AAV8) vector to overexpress a codon-optimised Klf15 cDNA under the muscle-specific Spc5-12 promoter (AAV8-Klf15). Administration of AAV8-Klf15 to severe Taiwanese Smn−/−;SMN2 or intermediate Smn2B/− SMA mice significantly increased Klf15 expression in muscle. We also observed significant activity of the AAV8-Klf15 vector in liver and heart. AAV8-mediated Klf15 overexpression moderately improved survival in the Smn2B/− model but not in the Taiwanese mice. An inability to specifically induce Klf15 expression at physiological levels in a time- and tissue-dependent manner may have contributed to this limited efficacy. Thus, our work demonstrates that an AAV8-Spc5-12 vector induces high gene expression as early as P2 in several tissues including muscle, heart and liver, but highlights the challenges of achieving meaningful vector-mediated transgene expression of Klf15.

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