Drug treatment for spinal muscular atrophy type I

Wadman, Renske I.; Bosboom, Wendy MJ; Berg, Leonard H van den; Wokke, John H. J.; Iannaccone, Susan T.; Vrancken, Alexander FJE

doi:10.1002/14651858.cd006281.pub3

Cited by 9 publications

(5 citation statements)

References 82 publications

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“…However, riluzole treatment increased levels of a hippocampal neuron maturation marker, synaptophysin, suggesting that riluzole may accelerate maturation with consequent decreases in SMN levels. Therefore, it might be worthwhile to investigate the synergistic effects of riluzole in combination with drugs that directly increase SMN levels (Wadman et al , 2011a; Wadman et al, 2011b). In summary, our studies demonstrate the beneficial impact of riluzole in SMA models and suggest that riluzole acts via SK channels to ameliorate SMN loss of function defects, delineating an important therapeutic pathway for neuromuscular disease patients.…”

Section: Discussionmentioning

confidence: 99%

The Neuroprotective Drug Riluzole Acts via Small Conductance Ca²⁺-Activated K⁺Channels to Ameliorate Defects in Spinal Muscular Atrophy Models

et al. 2013

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Spinal muscular atrophy (SMA), a recessive neuromuscular disorder, is caused by diminished function of the Survival Motor Neuron (SMN) protein. To define the cellular processes pertinent to SMA, parallel genetic screens were undertaken in Drosophila and C. elegans SMA models to identify modifiers of the SMN loss of function phenotypes. One class of such genetic modifiers was the small conductance, Ca2+-activated K+ (SK) channels. SK channels allow efflux of potassium ions when intracellular calcium increases and can be activated by the neuroprotective drug riluzole. The latter is the only drug with proven, albeit modest, efficacy in the treatment of Amyotrophic Lateral Sclerosis (ALS). It is unclear if riluzole can extend lifespan or ameliorate symptoms in SMA patients as previous studies were limited and of insufficient power to draw any conclusions. The critical biochemical target of riluzole in motorneuron disease is not known, but the pharmacological targets of riluzole include SK channels. We examine here the impact of riluzole in two different SMA models. In vertebrate neurons, riluzole treatment restored axon outgrowth caused by diminished SMN. Additionally, riluzole ameliorated the neuromuscular defects in a C. elegans SMA model and SK channel function was required for this beneficial effect. We propose that riluzole improves motorneuron function by acting on SK channels and suggest that SK channels may be important therapeutic targets for SMA patients.

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Section: Discussionmentioning

confidence: 99%

The Neuroprotective Drug Riluzole Acts via Small Conductance Ca²⁺-Activated K⁺Channels to Ameliorate Defects in Spinal Muscular Atrophy Models

et al. 2013

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“…Until recently no drug treatment had proved to be able to influence the disease course of SMA. A Cochrane review published in 2012 reported six randomized placebo-controlled trials on treatment for SMA using creatine, phenylbutyrate, gabapentin, thyrotropin-releasing hormone, hydroxyurea and combination therapy with valproate and acetyl-L-carnitine [36,37]. None of these studies showed statistically significant effects on the outcome measures in participants with SMA types 2 and 3.…”

Section: Medication Supplements and Immunizationsmentioning

confidence: 99%

Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics

Finkel

Mercuri

Meyer

et al. 2018

Neuromuscular Disorders

498

428

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This is the second half of a two-part document updating the standard of care recommendations for spinal muscular atrophy published in 2007. This part includes updated recommendations on pulmonary management and acute care issues, and topics that have emerged in the last few years such as other organ involvement in the severe forms of spinal muscular atrophy and the role of medications. Ethical issues and the choice of palliative versus supportive care are also addressed. These recommendations are becoming increasingly relevant given recent clinical trials and the prospect that commercially available therapies will likely change the survival and natural history of this disease.

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“…Natural history studies that document the rate of progression of motor deficits in specific SMA types and age groups are important for the design of clinical trials to test efficacy of disease-modifying therapies [5][6][7][8][9]. Recent studies have primarily focused on younger patients, in particular infants with SMA type 1 and children and teenagers with types 2 and 3.…”

Section: Introductionmentioning

confidence: 99%

Muscle strength and motor function throughout life in a cross‐sectional cohort of 180 patients with spinal muscular atrophy types 1c–4

Wadman¹,

Wijngaarde²,

Stam³

et al. 2018

Euro J of Neurology

151

139

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Drug treatment for spinal muscular atrophy type I

Cited by 9 publications

References 82 publications

The Neuroprotective Drug Riluzole Acts via Small Conductance Ca²⁺-Activated K⁺Channels to Ameliorate Defects in Spinal Muscular Atrophy Models

The Neuroprotective Drug Riluzole Acts via Small Conductance Ca²⁺-Activated K⁺Channels to Ameliorate Defects in Spinal Muscular Atrophy Models

Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics

Muscle strength and motor function throughout life in a cross‐sectional cohort of 180 patients with spinal muscular atrophy types 1c–4

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Drug treatment for spinal muscular atrophy type I

Cited by 9 publications

References 82 publications

The Neuroprotective Drug Riluzole Acts via Small Conductance Ca2+-Activated K+Channels to Ameliorate Defects in Spinal Muscular Atrophy Models

The Neuroprotective Drug Riluzole Acts via Small Conductance Ca2+-Activated K+Channels to Ameliorate Defects in Spinal Muscular Atrophy Models

Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics

Muscle strength and motor function throughout life in a cross‐sectional cohort of 180 patients with spinal muscular atrophy types 1c–4

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Product

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The Neuroprotective Drug Riluzole Acts via Small Conductance Ca²⁺-Activated K⁺Channels to Ameliorate Defects in Spinal Muscular Atrophy Models

The Neuroprotective Drug Riluzole Acts via Small Conductance Ca²⁺-Activated K⁺Channels to Ameliorate Defects in Spinal Muscular Atrophy Models