smn2 gene
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2021 ◽  
Vol 1 (9) ◽  
Author(s):  
Reimbursement Team

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses onasemnogene abeparvovec (Zolgensma), given as a single-dose IV infusion of 1.1 × 1014 vector genomes/kg Indication: For the treatment of pediatric patients with 5q SMA with biallelic mutations in the survival motor neuron 1 (SMN1) gene and: 3 or fewer copies of the SMN2 gene or infantile-onset SMA  


2021 ◽  
Vol 1 (8) ◽  
Author(s):  
Reimbursement Team

CADTH recommends that Evrysdi should be reimbursed by public drug plans for the treatment of spinal muscular atrophy (SMA) in patients aged 2 months and older, if certain conditions are met. Evrysdi should only be reimbursed if the patient is under the care of a specialist with experience in the diagnosis and management of SMA, it is not used in combination with nusinersen or onasemnogene abeparvovec, and the price is reduced. Evrysdi should only be reimbursed to treat patients aged 2 months to 7 months with genetic documentation of 2 or 3 copies of the survival motor neuron 2 (SMN2) gene or non-ambulatory patients aged 8 months to 25 years with genetic documentation of 2 or 3 copies of the SMN2 gene. Patients are ineligible if they currently require permanent invasive ventilation. After 12 months of treatment, patients should be assessed to ensure clinical benefit.


2021 ◽  
Vol 26 (5) ◽  
pp. 437-444
Author(s):  
Aimen Naveed ◽  
Hillary Calderon

Spinal muscular atrophy (SMA) is a debilitating disorder characterized by degeneration of large motor neurons. It is a heterogeneous group of disorders caused by a homozygous deletion in the survival motor neuron (SMN) gene on chromosome 5, resulting in a SMN protein deficiency. Small amounts of SMN protein are also produced by the SMN2 gene, which that differs from SMN1 by a single nucleotide. Spinal muscular atrophy types and phenotypic severity depend on the number of variations of the SMN2 gene and the amount of SMN2 protein produced. Because the SMN protein deficiency is the root cause of the disease, treatment strategies for SMA revolve around increasing SMN protein production. Nusinersen (Spinraza, Biogen, Cambridge, MA) was the only treatment option available for SMA until the FDA approved onasemnogene abeparvovec-xioi (Zolgensma, AveXis Inc, Bannockburn, IL), a one-time–administered adeno-associated viral vector–based gene therapy that delivers the SMN gene to the motor neuron cells. Data from clinical studies show significant improvement in motor milestone achievements and ventilator-free survival but are limited by approximately 5 years' worth of results. This one-time intravenous injection of this new gene therapy also bears a hefty price tag; however, it may be more cost effective in the long run versus the multiple intrathecal administrations needed with nusinersen. Drug access and use are hindered by drug cost, payer reimbursement issues, and lack of long-term data from clinical studies. Questions also remain regarding the safety and efficacy of repeated drug administration for patients with advanced disease.


2021 ◽  
Author(s):  
Laura Blasco‐Pérez ◽  
Ida Paramonov ◽  
Jordi Leno ◽  
Sara Bernal ◽  
Laura Alias ◽  
...  
Keyword(s):  

Neurogenetics ◽  
2021 ◽  
Author(s):  
Deborah L. Stabley ◽  
Jennifer Holbrook ◽  
Mena Scavina ◽  
Thomas O. Crawford ◽  
Kathryn J. Swoboda ◽  
...  

2021 ◽  
Vol 8 ◽  
pp. 2329048X2110087
Author(s):  
Katarzyna Pierzchlewicz ◽  
Izabela Kępa ◽  
Jacek Podogrodzki ◽  
Katarzyna Kotulska

Spinal muscular atrophy (SMA) is a genetic condition characterized by progressive motoneuron loss. Infants affected by SMA type 1 do not gain developmental milestones and acutely decline, requiring ventilatory support. Several scales are used to assess motor disability and its progression in SMA. Recently, 3 disease-modifying therapies have been approved for SMA patients: nusinersen, an intrathecal antisense oligonucleotide enhancing SMN protein production by the SMN2 gene, risdiplam, also influencing the SMN2 gene to stimulate SMN production but administered orally, and onasemnogene abeparvovec-xioi, an SMN1 gene replacement therapy. Thus, the functional scales should now be applicable for patients improving their motor function over time to assess treatment efficacy. In this paper, we compare different functional scales used in SMA patients. Their usefulness in different SMA types, age groups, and feasibility in daily clinical practice is described below. Some changes in motor function assessments in SMA are also suggested.


2020 ◽  
Author(s):  
Yingjie Sun ◽  
Xiangdong Kong ◽  
Zhenhua Zhao ◽  
Xuechao Zhao

Abstract Background Spinal muscular atrophy (SMA) is a common and lethal autosomal recessive neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene. At present, gene therapy medicine for SMA, i.e., Spinraza (Nusinersen), has been approved by the FDA, bringing hope to SMA patients and families. Accurate diagnosis is essential for treatment. Our goal was to detect genetic mutations in SMA patients in China and to show the results of the prenatal diagnosis of SMA.Methods In this study, we examined 419 patients in our hospital from January 2010 to September 2019. Multiplex ligation-dependent probe amplification analysis was used to determine the copy numbers of SMN1 and SMN2. Long-range PCR combined with nested PCR was used to detect point mutations in SMN1. In addition to the above detection methods, we also used QF-PCR in prenatal diagnosis to reduce the impact of maternal contamination. We conducted a total of 339 prenatal diagnoses from January 2010 to September 2019.Results Homozygous deletion of SMN1 exon 7 was detected in 96.40% (404/419) of patients. Homozygous deletion of SMN1 exon 7 alone was detected in 15 patients (3.60%). In total, 10 point mutations were detected in the 15 pedigrees. Most patients with SMA Type I have 1~2 copies of the SMN2 gene. Patients with SMA Type II have 2 or 3 copies of the SMN2 gene. The results of prenatal diagnoses showed that 118 fetuses were normal, 149 fetuses were carriers of heterozygous variants, and the remaining 72 fetuses harbored compound heterozygous variants or homozygous variants. Conclusions Our study found that the most common mutation in SMA was homozygous deletion of SMN1 exon 7 in our study. We suggest that detecting only the deletion of exon 7 of SMN1 can meet most of the screening needs. We also believe that SMN2 copy numbers can help infer the disease classification and provide some reference for future treatment options.


2020 ◽  
Author(s):  
Yingjie Sun ◽  
Xiangdong Kong ◽  
Zhenhua Zhao ◽  
Xuechao Zhao

Abstract Background Spinal muscular atrophy (SMA) is a common and lethal autosomal recessive neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene. At present, gene therapy medicine for SMA, i.e., Spinraza (Nusinersen), has been approved by the FDA, bringing hope to SMA patients and families. Accurate diagnosis is essential for treatment. Our goal was to detect genetic mutations in SMA patients in China and to show the results of the prenatal diagnosis of SMA.Methods In this study, we examined 419 patients in our hospital from January 2010 to September 2019. Multiplex ligation-dependent probe amplification analysis was used to determine the copy numbers of SMN1 and SMN2. Long-range PCR combined with nested PCR was used to detect point mutations in SMN1. In addition to the above detection methods, we also used QF-PCR in prenatal diagnosis to reduce the impact of maternal contamination. We conducted a total of 339 prenatal diagnoses from January 2010 to September 2019.Results Homozygous deletion of SMN1 exon 7 was detected in 96.40% (404/419) of patients. Homozygous deletion of SMN1 exon 7 alone was detected in 15 patients (3.60%). In total, 10 point mutations were detected in the 15 pedigrees. Most patients with SMA Type I have 1~2 copies of the SMN2 gene. Patients with SMA Type II have 2 or 3 copies of the SMN2 gene. The results of prenatal diagnoses showed that 118 fetuses were normal, 149 fetuses were carriers of heterozygous variants, and the remaining 72 fetuses harbored compound heterozygous variants or homozygous variants. Conclusions Our study found that the most common mutation in SMA was homozygous deletion of SMN1 exon 7 in our study. We suggest that detecting only the deletion of exon 7 of SMN1 can meet most of the screening needs. We also believe that SMN2 copy numbers can help infer the disease classification and provide some reference for future treatment options.


2020 ◽  
Vol 40 (03) ◽  
pp. 335-341
Author(s):  
Alex J. Fay ◽  
Renatta Knox ◽  
Erin E. Neil ◽  
Jonathan Strober

AbstractIn the past decade, the number of genes linked to neuromuscular diseases of childhood has expanded dramatically, and this genetic information is forming the basis for gene-specific and even mutation-specific therapies. At the forefront of these advances are the two recently approved treatments for spinal muscular atrophy: one, an antisense oligonucleotide that modifies splicing of the SMN2 gene, and, the other, a gene therapy vector that delivers the SMN1 gene to motor neurons, both of which are allowing patients to acquire developmental milestones previously unseen in this fatal disease. This review highlights these advances and emerging targeted therapies for Duchenne muscular dystrophy and centronuclear myopathy, while also covering enzyme replacement therapy and small molecule-based targeted therapies for conditions such as Pompe's disease and congenital myasthenic syndromes. With these and other newer techniques for targeted correction of genetic defects, such as CRISPR/Cas9, there is now hope that treatments for many more genetic diseases of the nervous system will follow in the near future.


2020 ◽  
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