Nusinersen: First Global Approval

Hoy, Sheridan M.

doi:10.1007/s40265-017-0711-7

Cited by 194 publications

(139 citation statements)

References 7 publications

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“…With a new treatment for SMA, Spinraza (Nusinersen), approved by the FDA and EMA, it is now critically important to understand these cardiovascular pathologies. The drug is administered intrathecally and therefore only targets the central nervous system (Hoy, ), which appears to limit its utility in disease treatment (Finkel et al. ).…”

Section: Discussionmentioning

confidence: 99%

Developmental and degenerative cardiac defects in the Taiwanese mouse model of severe spinal muscular atrophy

et al. 2018

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Spinal muscular atrophy (SMA), an autosomal recessive disease caused by a decrease in levels of the survival motor neuron (SMN) protein, is the most common genetic cause of infant mortality. Although neuromuscular pathology is the most severe feature of SMA, other organs and tissues, including the heart, are also known to be affected in both patients and animal models. Here, we provide new insights into changes occurring in the heart, predominantly at pre- and early symptomatic ages, in the Taiwanese mouse model of severe SMA. Thinning of the interventricular septum and dilation of the ventricles occurred at pre- and early symptomatic ages. However, the left ventricular wall was significantly thinner in SMA mice from birth, occurring prior to any overt neuromuscular symptoms. Alterations in collagen IV protein from birth indicated changes to the basement membrane and contributed to the abnormal arrangement of cardiomyocytes in SMA hearts. This raises the possibility that developmental defects, occurring prenatally, may contribute to cardiac pathology in SMA. In addition, cardiomyocytes in SMA hearts exhibited oxidative stress at pre-symptomatic ages and increased apoptosis during early symptomatic stages of disease. Heart microvasculature was similarly decreased at an early symptomatic age, likely contributing to the oxidative stress and apoptosis phenotypes observed. Finally, an increased incidence of blood retention in SMA hearts post-fixation suggests the likelihood of functional defects, resulting in blood pooling. These pathologies mirror dilated cardiomyopathy, with clear consequences for heart function that would likely contribute to potential heart failure. Our findings add significant additional experimental evidence in support of the requirement to develop systemic therapies for SMA capable of treating non-neuromuscular pathologies.

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Section: Discussionmentioning

confidence: 99%

Developmental and degenerative cardiac defects in the Taiwanese mouse model of severe spinal muscular atrophy

et al. 2018

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“…Nusinersen is an antisense oligonucleotide that alters the splicing of SMN2 pre-mRNA to promote expression of fulllength SMN protein [7 , 21-23] and is the first disease-modifying treatment approved for SMA [24] . In clinical studies in a range of symptomatic children across several SMA populations, nusinersen demonstrated significant and clinically meaningful benefit as assessed by achievement of motor milestones, measures of motor function, and survival in those with infantile-onset SMA, along with a favorable safety profile [8 , 9 , 25] .…”

Section: Introductionmentioning

confidence: 99%

Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study

Vivo

Bertini

Swoboda

et al. 2019

Neuromuscular Disorders

419

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Spinal muscular atrophy (SMA) is a neurodegenerative disease associated with severe muscle atrophy and weakness in the limbs and trunk. We report interim efficacy and safety outcomes as of March 29, 2019 in 25 children with genetically diagnosed SMA who first received nusinersen in infancy while presymptomatic in the ongoing Phase 2, multisite, open-label, single-arm NURTURE trial. Fifteen children have two SMN2 copies and 10 have three SMN2 copies. At last visit, children were median (range) 34.8 [25.7-45.4] months of age and past the expected age of symptom onset for SMA Types I or II; all were alive and none required tracheostomy or permanent ventilation. Four (16%) participants with two SMN2 copies utilized respiratory support for ≥6 h/day for ≥7 consecutive days that was initiated during acute, reversible illnesses. All 25 participants achieved the ability to sit without support, 23/25 (92%) achieved walking with assistance, and 22/25 (88%) achieved walking independently. Eight infants had adverse events considered possibly related to nusinersen by the study investigators. These results, representing a median 2.9 years of follow up, emphasize the importance of proactive treatment with nusinersen immediately after establishing the genetic diagnosis of SMA in presymptomatic infants and emerging newborn screening efforts.

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“…It is caused by homozygous disruption of the survival motor neuron 1 (SMN1) gene either by deletion, conversion, or mutation. There are no medical treatments for SMA except for the anti‐sense oligonucleotide SPINRAZA® (nusinersen) . Several investigations have elucidated possible mechanisms underlying the molecular pathogenesis of the disease proposing the role of the oxidative stress in the progression of SMA.…”

Section: Curcumin In Neurodegenerative Diseasesmentioning

confidence: 99%

Benefits of curcumin in brain disorders

et al. 2019

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Curcumin is widely consumed in Asia either as turmeric directly or as one of the culinary ingredients in food recipes. The benefits of curcumin in different organ systems have been reported extensively in several neurological diseases and cancer. Curcumin has got its global recognition because of its strong antioxidant, anti‐inflammatory, anti‐cancer, and antimicrobial activities. Additionally, it is used in diabetes and arthritis as well as in hepatic, renal, and cardiovascular diseases. Recently, there is growing attention on usage of curcumin to prevent or delay the onset of neurodegenerative diseases. This review summarizes available data from several recent studies on curcumin in various neurological diseases such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Huntington's disease, Prions disease, stroke, Down's syndrome, autism, Amyotrophic lateral sclerosis, anxiety, depression, and aging. Recent advancements toward increasing the therapeutic efficacy of curcuma/curcumin formulation and the novel delivery strategies employed to overcome its minimal bioavailability and toxicity studies have also been discussed. This review also summarizes the ongoing clinical trials on curcumin for different neurodegenerative diseases and patent details of curcuma/curcumin in India.

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Nusinersen: First Global Approval

Cited by 194 publications

References 7 publications

Developmental and degenerative cardiac defects in the Taiwanese mouse model of severe spinal muscular atrophy

Developmental and degenerative cardiac defects in the Taiwanese mouse model of severe spinal muscular atrophy

Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study

Benefits of curcumin in brain disorders

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