Muscle impairment in MRI affect variability in treatment response to nusinersen in patients with spinal muscular atrophy type 2 and 3: A retrospective cohort study

Shimizu‐Motohashi, Yuko; Chiba, Emiko; Mizuno, Katsuhiro; Yajima, Hiroyuki; Ishiyama, Akihiko; Takeshita, Eri; Sato, Noriko; Oba, Mari S.; Sasaki, Masayuki; Ito, Shuichi; Komaki, Hirofumi

doi:10.1016/j.braindev.2022.11.002

Cited by 7 publications

(4 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is the most drastic and rarest form of SMA, with onset in womb or within the first few days of life. Neonate with SMA type 0 often exhibit severe muscle weakness and may not survive beyond a few months (15).…”

Section: Sma Typementioning

confidence: 99%

Diving into progress: a review on current therapeutic advancements in spinal muscular atrophy

Bagga,

Singh,

Ram

et al. 2024

Front. Neurol.

View full text Add to dashboard Cite

Spinal muscular atrophy (SMA) is an uncommon disorder associated with genes characterized by the gradual weakening and deterioration of muscles, often leading to substantial disability and premature mortality. Over the past decade, remarkable strides have been made in the field of SMA therapeutics, revolutionizing the landscape of patient care. One pivotal advancement is the development of gene-targeted therapies, such as nusinersen, onasemnogene abeparvovec and risdiplam which have demonstrated unprecedented efficacy in slowing disease progression. These therapies aim to address the root cause of SMA by targeting the survival motor neuron (SMN) gene, effectively restoring deficient SMN protein levels. The advent of these innovative approaches has transformed the prognosis for many SMA patients, offering a glimmer of hope where there was once limited therapeutic recourse. Furthermore, the emergence of small molecule compounds and RNA-targeting strategies has expanded the therapeutic arsenal against SMA. These novel interventions exhibit diverse mechanisms of action, including SMN protein stabilization and modulation of RNA splicing, showcasing the multifaceted nature of SMA treatment research. Collective efforts of pharmaceutical industries, research centers, and patient advocacy groups have played an important role in expediting the translation of scientific discoveries into visible clinical benefits. This review not only highlights the remarkable progress achieved in SMA therapeutics but also generates the ray of hope for the ongoing efforts required to enhance accessibility, optimize treatment strategies, rehabilitation (care and therapies) and ultimately pave the way for an improved quality of life for individuals affected by SMA.

show abstract

Section: Sma Typementioning

confidence: 99%

Diving into progress: a review on current therapeutic advancements in spinal muscular atrophy

Bagga,

Singh,

Ram

et al. 2024

Front. Neurol.

View full text Add to dashboard Cite

show abstract

“…[ [128][129][130][131][132][133] Electrical impedance myography (EIM) EIM measures action potentials on the surface of muscles following stimulation and has been shown to be sensitive to nuanced advancement of disease progression.…”

Section: Imaging Candidatesmentioning

confidence: 99%

“…Other recent candidate biomarkers include genetic factors such as SMN2 copy number [ 10 , 13 – 15 , 81 , 82 ], SMN2 polymorphisms [ 10 , 13 – 16 , 81 – 83 ], and modifier genes [ 73 , 84 – 89 ]; transcription and splicing regulators, such as microRNAs [ 90 – 94 ], methylation factors [ 95 – 99 ], and long non-coding RNAs [ 100 – 103 ]; biomolecular factors such as SMN protein [ 18 , 39 , 48 , 57 , 81 , 104 – 106 ], neurofilament (NF) [ 78 , 107 – 118 ], tau protein [ 112 , 119 – 121 ], and muscle damage indicators [ 122 – 124 ]; muscle imaging parameters including magnetic resonance imaging (MRI) [ 122 – 124 ] and electrical impedance myography (EIM) [ 75 , 125 – 127 ]; and electrophysiological parameters including compound muscle action potential (CMAP) [ 128 – 133 ], motor unit number estimation (MUNE) [ 75 , 125 – 127 ], and repetitive nerve stimulation [ 45 , 75 , 134 – 138 ].…”

Section: Introductionmentioning

confidence: 99%

Identifying Biomarkers of Spinal Muscular Atrophy for Further Development

Glascock,

Darras,

Crawford

et al. 2023

JND

View full text Add to dashboard Cite

Background: Spinal muscular atrophy (SMA) is caused by bi-allelic, recessive mutations of the survival motor neuron 1 (SMN1) gene and reduced expression levels of the survival motor neuron (SMN) protein. Degeneration of alpha motor neurons in the spinal cord causes progressive skeletal muscle weakness. The wide range of disease severities, variable rates of decline, and heterogenous clinical responses to approved disease-modifying treatment remain poorly understood and limit the ability to optimize treatment for patients. Validation of a reliable biomarker(s) with the potential to support early diagnosis, inform disease prognosis and therapeutic suitability, and/or confirm response to treatment(s) represents a significant unmet need in SMA. Objectives: The SMA Multidisciplinary Biomarkers Working Group, comprising 11 experts in a variety of relevant fields, sought to determine the most promising candidate biomarker currently available, determine key knowledge gaps, and recommend next steps toward validating that biomarker for SMA. Methods: The Working Group engaged in a modified Delphi process to answer questions about candidate SMA biomarkers. Members participated in six rounds of reiterative surveys that were designed to build upon previous discussions. Results: The Working Group reached a consensus that neurofilament (NF) is the candidate biomarker best poised for further development. Several important knowledge gaps were identified, and the next steps toward filling these gaps were proposed. Conclusions: NF is a promising SMA biomarker with the potential for prognostic, predictive, and pharmacodynamic capabilities. The Working Group has identified needed information to continue efforts toward the validation of NF as a biomarker for SMA.

show abstract

“…Clinical evolution of treated and non-treated patients is usually performed using neuromuscular evaluations of muscle strength, motor capacities and bulbar and respiratory function. Clinical tools such as SC imaging (29), muscle MRI (30,31) and neurophysiology (motor unit count) (32,33) are being explored as possible biomarkers for the follow-up of patients. However, more specific, and sensitive biomarkers capable of assessing the effect of the treatment and of predicting disease trajectories over time are still partially lacking.…”

mentioning

confidence: 99%

Role of circulating biomarkers in spinal muscular atrophy: insights from a new treatment era

Giorgia,

Gomez Garcia de la Banda,

Smeriglio

2023

Front. Neurol.

View full text Add to dashboard Cite

Spinal muscular atrophy (SMA) is a lower motor neuron disease due to biallelic mutations in the SMN1 gene on chromosome 5. It is characterized by progressive muscle weakness of limbs, bulbar and respiratory muscles. The disease is usually classified in four different phenotypes (1–4) according to age at symptoms onset and maximal motor milestones achieved. Recently, three disease modifying treatments have received approval from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), while several other innovative drugs are under study. New therapies have been game changing, improving survival and life quality for SMA patients. However, they have also intensified the need for accurate biomarkers to monitor disease progression and treatment efficacy. While clinical and neurophysiological biomarkers are well established and helpful in describing disease progression, there is a great need to develop more robust and sensitive circulating biomarkers, such as proteins, nucleic acids, and other small molecules. Used alone or in combination with clinical biomarkers, they will play a critical role in enhancing patients’ stratification for clinical trials and access to approved treatments, as well as in tracking response to therapy, paving the way to the development of individualized therapeutic approaches. In this comprehensive review, we describe the foremost circulating biomarkers of current significance, analyzing existing literature on non-treated and treated patients with a special focus on neurofilaments and circulating miRNA, aiming to identify and examine their role in the follow-up of patients treated with innovative treatments, including gene therapy.

show abstract

Muscle impairment in MRI affect variability in treatment response to nusinersen in patients with spinal muscular atrophy type 2 and 3: A retrospective cohort study

Cited by 7 publications

References 31 publications

Diving into progress: a review on current therapeutic advancements in spinal muscular atrophy

Diving into progress: a review on current therapeutic advancements in spinal muscular atrophy

Identifying Biomarkers of Spinal Muscular Atrophy for Further Development

Role of circulating biomarkers in spinal muscular atrophy: insights from a new treatment era

Contact Info

Product

Resources

About