Prospective Cohort Study of Nusinersen Treatment in Adults with Spinal Muscular Atrophy

Yeo, Crystal Jing Jing; Simeone, Sarah D; Townsend, Elise L.; Zhang, Ren Zhe; Swoboda, Kathryn J.

doi:10.3233/jnd-190453

Cited by 56 publications

(60 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The cases reported above might suggest further evidence on the effects of nusinersen in stabilizing the disease course in adult SMA patients [4]; in fact HFMSE and RULM scores have remained stable after two years of therapy and these results are in line with what reported by Yeo and colleagues who observed a substantial stability of these scores in a cohort of 6 SMA type 3 patients followed for 12 months during treatment with nusinersen.…”

Section: Discussionsupporting

confidence: 86%

“…Recent studies have demonstrated the role of DTI in the detection and quantification of muscle fibers fat replacement [ 20 , Table 1 ]; FA is a parameter used to quantify the directional orientation of water molecules within the fibers; FA values are ranged between 0 and 1: in principle, when [ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] ] tissues are intact, water is forced to move in a specific direction and the FA value is close to 1; unexpectedly patients with severe fat replacement show positive correlation with FA values and negative correlation with Apparent Diffusion Coefficient (ADC); a possible explanation is the artificial increase of FA values in patients with more than 40–45% fat muscle infiltration [ 25 ]. In our cases DTI showed that nusinersen treatment may have a positive effect on size, length and organization of fiber tracts raising the potential neurogenic rescue even in long-standing chronic SMA patients.…”

Section: Discussionmentioning

confidence: 99%

“…Spinal Muscular Atrophy (SMA) is an autosomal-recessive disorder caused by mutations in SMN1 gene, leading to degeneration of alpha motor neurons in the spinal cord resulting in progressive muscle weakness and disability [ [1] , [2] , [3] ]. The results from the pivotal [ 4 ] and more recent trials [ 5 ] with intrathecal nusinersen treatment, as well as the results from real world data [ 6 ], have created great expectations in older patients having long-lasting muscular atrophy and weakness; in fact there is growing evidence that treatment is at the very least stabilizing or providing some degree of improvement in motor function [ 7 ]. However, there are still some critical issues in understanding results in adults, including the lack of natural history data and outcome measures to monitor disease progression [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Muscle MRI in two SMA patients on nusinersen treatment: A two years follow-up

Barp

Carraro

Albamonte

et al. 2020

Journal of the Neurological Sciences

View full text Add to dashboard Cite

Introduction: The effects of nusinersen in adults with SMA rely on neuromotor function scales and qualitative assessments. There are limited clinical or imaging data on muscle changes over time. Methods: Two adult SMA patients underwent clinical assessments including measures of upper and lower limb function with Revised Upper Limb Module (RULM) and Hammersmith Function Motor Scale Expanded (HFMSE); both patients were also studied with whole-body muscle MRI (T1-weighted and Diffusion Tensor Imaging/DTI sequences), at baseline and after 10 and 24 months from the beginning of treatment with nusinersen. Results: After two years of treatment, HFMSE and RULM scores were stable in both patients. DTI sequences revealed an increased number, length and organization of muscle fiber tracks, and Fractional Anisotropy (FA) values showed a significant reduction after 10 and 24 months from baseline, in their corresponding maps. Discussion: Muscle DTI imaging seems to play an interesting role to monitor treatment effects over time in adult SMA patients.

show abstract

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Muscle MRI in two SMA patients on nusinersen treatment: A two years follow-up

Barp

Carraro

Albamonte

et al. 2020

Journal of the Neurological Sciences

View full text Add to dashboard Cite

show abstract

“…Nusinersen was the first FDA-approved treatment and was approved for all SMA types (11). The approval of nusinersen was based on robust data from infants and children (12)(13)(14), but data in adults is more limited (15)(16)(17)(18)(19)(20)(21)(22). The goals of this study were to investigate the safety, tolerabilty and treatment effect of nusinersen in older, more severely affected, non-ambulatory individuals with SMA.…”

Section: Introductionmentioning

confidence: 99%

Safety, Tolerability, and Effect of Nusinersen in Non-ambulatory Adults With Spinal Muscular Atrophy

et al. 2021

View full text Add to dashboard Cite

Objective: Investigation of the safety, tolerability, and treatment effect of nusinersen treatment in non-ambulatory adults with spinal muscular atrophy (SMA).Methods: Non-ambulatory individuals, aged 18 years or older with genetically confirmed 5q SMA were enrolled. In participants with spinal fusion, fluoroscopy guided cervical C1–C2 lateral approach was used. Outcomes at 2, 6, 10, and 14 months post-treatment were compared with baseline assessment. Forced vital capacity (FVC) was the primary outcome, and RULM, HFMSE, the modified SMA-FRS, and ulnar nerve electrophysiology [compound muscle action potential (CMAP), single motor unit size, and motor unit number] were secondary. Adverse and serious adverse events and clinically significant vital sign or lab abnormalities were recorded.Results: Results from 12 women and 7 men (mean age: 39.7 ± 13.9, range: 21–64 years) were analyzed. No clinically significant changes of vital signs or laboratory parameters were observed. Five participants were hospitalized for pneumonia. Other adverse events included headache, back pain, cervical injection site pain, and upper respiratory and urinary tract infections. High baseline protein/creatinine ratio without significant change on treatment noted in 4 participants. FVC was feasible in all participants. HFMSE and RULM were not feasible in the majority of participants. FVC and functional outcomes were stable without improvement. CMAP and single motor unit potential sizes showed enlargement while motor unit numbers were stable.Conclusions: Nusinersen, including C1/C2 delivery, was safe overall and well-tolerated. Several outcome measures were limited by floor effect. Overall, treatment resulted in stability of motor outcomes, but motor unit and CMAP size were increased.

show abstract

“…4 This implies a therapeutic window for SMN rescue treatment even in late stages of disease when many motor neurons are already lost in pediatric and adult patients with SMA. 5 Nusinersen, onasemnogene abeparvovec-xioi, and risdiplam primarily target the motor neurons, which drive death in SMA; however, due to systemic modes of administration, onasemnogene abeparvovec-xioi and risdiplam also act on peripheral tissues. It is important to consider the therapeutic window, define cell targets of gene therapies, and decide on therapeutic regimes based on our understanding of SMA pathology.…”

mentioning

confidence: 99%