SMA Patients Research Articles

The socioeconomic burden of spinal muscular atrophy in Saudi Arabia: a cross-sectional pilot study.

Spinal muscular atrophy (SMA) is a rare debilitating condition with a significant burden for patients and society. However, little is known about how it affects Saudi Arabia's population. The socioeconomic and medical characteristics of affected SMA patients and their caregivers are lacking. This study aimed to describe the socioeconomic and medical characteristics of SMA patients and caregivers in Saudi Arabia. A cross-sectional questionnaire-based study was conducted using snowball sampling. Assessment tools including EuroQol (EQ-5D-5L) and visual analog scale (EQ-VAS), Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire (PHQ-9), and Costs for Patients Questionnaire (CoPaQ) were used to assess the quality of life (QoL), anxiety, depression, and out-of-pocket expenditures. Sixty-four caregivers of SMA patients participated. Type I patients had higher sibling concordance, ICU hospitalization, and mechanical support needs. Type III patients had better QoL. Type I patients' caregivers had higher depression scores. Type III patients' caregivers had higher out-of-pocket expenditures. Forty-eight percent received supportive care, while others received SMA approved therapies. SMA imposes a significant socioeconomic burden on patients and caregivers, requiring more attention from the healthcare system. Access to innovative therapies varied across SMA types. Pre-marital screening and early detection are crucial to reduce disease incidence and ensure timely treatment.

Impaired Neurodevelopment in Children with 5q-SMA - 2 Years After Newborn Screening.

Numerous studies have consistently found that reduced SMN protein expression does not severely affect cognitive function in SMA patients. However, the average intelligence quotient of SMA patients has ranged above to below average in different studies. The cognitive development of SMA patients identified through newborn screening remains largely unknown. 40 of 47 eligible SMA patients (23 females/17 males) from 39 families identified through newborn screening between January 2018 and December 2020 underwent developmental testing using Bayley III (BSID) after the 2 years of age. The mean age was 29.25 months (23-42 months). 17 patients had 2, 11 patients had 3 and 12 patients had ≥4 copies of SMN2. cognitive scale: mean 94.55 (SD 24.01); language scale: mean 86.09 (SD 26.41); motor scale: 81.28 (SD 28.07). Overall, the cognitive scales show that 14 children were below average, 20 children were average and 6 children were above average. 10/14 children with below average scores had 2 SMN2 copies. The post-hoc pairwise comparisons showed that the cognition main scale was significantly more sensitive to the number of SMN2 copies than the motor main scale of the BSID (MΔ= 10.27, p = 0.014). There is also evidence that cognition scored higher than the language main scale (MΔ= 7.11, p = 0.090). The impaired cognitive development of SMA children with 2 SMN2 copies, despite early initiation of therapy, underscores the critical role of the SMN protein in the early stages of brain development.

Gray and white matter abnormalities in children with type 2 and 3 SMA: A morphological assessment.

Type 2 and 3 children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. The lack of SMN protein possibly interacted with cerebellar structural changes in somatosensory areas. • MRI has found brain changes in SMA patients, however, there is no unified conclusion and lack of correlation with clinical degree in children SMA with type 2-3. • Type II and II children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. Cerebellar structural changes in somatosensory areas may attribute to the lack of SMN protein.

Paradoxical increase of neurofilaments in SMA patients treated with onasemnogene abeparvovec-xioi.

Neurofilament light chain (NfL) has been proposed as a biomarker reflecting disease severity and therapy response in children with spinal muscular atrophy type 1 and 2 (SMA1 and 2). The objective of this study was to examine how serum NfL changes after gene replacement therapy (GRT) with onasemnogene abeparvovec-xioi. We measured NfL in serum probes from 19 patients (10 SMA 1 and 6 SMA 2; 15 previously treated with nusinersen or risdiplam; 12 male) before and at variable time points after GRT. These values were related to motor scores (CHOP-Intend, HFMSE and RULM). Median age at GRT was 19 months (range 2-46 months). Median NfL of all patients before GRT was 39 pg/ml (range 0-663 pg/ml; normal values <25 pg/ml), increased significantly to 297 pg/ml (range 61-1,696 pg/ml; p<0,002) 1 month after GRT, and decreased to 49 pg/ml (range 24-151 pg/ml) after 6 months. Subjects pre-treated with nusinersen or risdiplam had lower baseline NfL levels than naïve patients (p<0,005), but absolute increases of NfL were similar in both groups. While motor scores were improved in 14 out of 18 SMA patients (78%) 6 months after GRT NfL values differed not significantly from those measured at baseline (p = 0,959). Serum NfL showed a paradoxical transient increase after GRT in both, pre-treated and naïve patients, which may reflect an immunological reaction in the CNS related to transfection of neuronal cells by AAV9. The clinical meaning of this increase should be assessed in future studies. Our findings encourage regular monitoring of NfL in OA treated patients.

Study on the efficacy, safety, and biomarkers of nusinersen in type II and III spinal muscular atrophy in children.

The time span for the approval of nusinersen to treat SMA remains short. Most studies on the efficacy and safety of this drug within clinical trials, are lacking real-world research data. This study is based on real-world studies of SMA patients in children with type II and III SMA and is committed to objectively evaluating the effectiveness and safety of this drug. A retrospective analysis was conducted on the clinical data of 18 children with type II and III SMA from January 2022 to June 2023. The motor function assessment scale, SMN protein, platelet, liver and kidney function, and other laboratory indicators of all patients before and after treatment were collected for statistical analysis. After load dose treatment (after 64 days of treatment), compared with baseline, the Revised Upper Limb Module (RULM) of SMA patients showed significant improvement (improvement rate: 44%), confirming the short-term effectiveness of the drug. The increase in cerebrospinal fluid SMN protein was greater in patients with significant improvement in motor function than in patients without improvement in motor function. Compared with baseline, there was no significant increase in AST and ALT levels in SMA patients, indicating that the drug had almost no effect on the liver. After each treatment, thrombocytopenia and partial urinary protein positivity may occur, but it could recover before the next treatment. This indicates that nusinersen is potentially harmful to platelet and renal function, although the effect is weak and reversible. Nusinersen has shown good efficacy and overall safety, but platelets and urinary protein are still indicators that require long-term monitoring. The increase in cerebrospinal fluid SMN protein was greater in patients with significant improvement in motor function than in patients without improvement in motor function.

Correlations between clinical motor scores and CMAP in patients with type 2 spinal muscular amyotrophy treated with nusinersen

BackgroundSpinal muscular atrophy (SMA) is a neuromuscular disorder characterized by the degeneration of the anterior horn cells of the spinal cord. Nusinersen for the treatment of SMA has been covered by public healthcare in France since May 2017. ObjectiveOur aim was to investigate whether there is a correlation between clinical and compound motor action potential (CMAP) measurements in SMA patients treated with nusinersen after 3 years’ follow-up. MethodMotor skills were evaluated regularly between M0 and M36 using the Motor Function Measure (MFM) score. CMAP measurements were collected regularly between M0 and M22. ResultsData for 10 patients with SMA type 2 were collected and divided into two age groups (< 5 years and > 5 years). Motor function improved, but not significantly, regarding distal motor skills (D3) in both groups, and in axial and proximal motor function (D2) in the younger group. CMAP measurements improved in all patients. CMAP increased significantly for the median nerve, and this improvement correlated significantly with global MFM and with axial and proximal tone (D2). ConclusionOur study shows gain in distal motor function with nusinersen, especially in younger patients with SMA type 2. These results encourage the screening of SMA patients and treatment as early as possible. CMAP measurements of the median nerve show clear improvement in patients treated with nusinersen and could be performed as routine follow-up.

Gene therapy in spinal muscular atrophy

Infantile SMA is a neuromuscular disease caused by the motor neuron degeneration, depending on the age of appearance of clinical signs and the evolution of the disease, three types of decreasing severity have been defined. SMA is caused by mutations or deletions of the SMN1 gene and disease. Various therapies aimed at increasing SMN protein levels have been developed. Gene therapy is part of the therapeutic arsenal now available for the treatment of SMA under certain conditions. It uses the scAAV9 vector carrying a functional copy of SMN1 to restore SMN protein expression at the cellular level. Because the adeno-associated virus genome is maintained as it is an episome, a single intravenous administration is sufficient to producing a long-lasting therapeutic effect. The effectiveness of gene replacement therapy in patients with SMA has been demonstrated in various studies. It is now clear that treatment as early as possible provides better clinical results. However, this treatment must be carried out in a suitable medical environment, with close monitoring initially due to potentially serious side effects. In France, this treatment has been available since 2019. A national committee of experts involved in the treatment of pediatric SMA patients has established that pediatric patients with SMA decide on the indications for disease-modifying therapies (DMT) in children. The French Spinal Muscular Atrophy Registry (SMA France Registry) was established in January 2020. The registry includes all patients with genetically confirmed SMN1-related SMA. All patients treated with GT are systematically included in the registry. As of July 21, 2023: 72 patients with SMA have been treated with GT in France since June 2019. The arrival of new treatments reveals new clinical phenotypes of SMA which constitute a new management challenge. Treatment as early as possible is also a very important factor for a favorable outcome and calls for presymptomatic screening. However, the arrival of these new treatments, extremely expensive raises other socio-economic questions. © 2023 Published by Elsevier Masson SAS on behalf of French Society of Pediatrics.

Respiratory function in a large cohort of treatment-naïve adult spinal muscular atrophy patients: a cross-sectional study

Due to poor data in literature, we aimed to investigate the respiratory function in a large cohort of naïve Italian adult (≥18 years) SMA patients in a multi-centric cross-sectional study. The following respiratory parameters were considered: forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and need for non-invasive ventilation (NIV). We included 145 treatment-naïve adult patients (SMA2=18, SMA3=125; SMA4=2), 58 females (40 %), with median age at evaluation of 37 years (range 18–72). Fifty-six (37 %) and 41 (31 %) patients had abnormal (<80 %) values of FVC and FEV1, respectively. Fourteen (14 %) patients needed NIV, started at median age of 21 (range 4–68). Motor function, measured by Hammersmith Functional Motor Scale Expanded and Revised Upper Limb Module as well as SMA2, loss of walking ability, surgery for scoliosis, use of NIV, and cough assisting device (CAD) were all significantly associated to lower FVC and FEV1 values, while no association with age at baseline, disease duration, gender or 6 min walking test was observed, except for a correlation between FVC and age in SMA3 walkers (p < 0.05). In conclusion, respiratory function in adult SMA patients is relatively frequently impaired, substantially stable, and significantly correlated with motor function and disease severity.

P07 Does spinal surgery hinder intrathecal nusinersen injections in paediatric SMA patients?

P07 Does spinal surgery hinder intrathecal nusinersen injections in paediatric SMA patients?

Modified nusinersen intrathecal injection method: inclusion of a septal needle-free closed infusion connector.

Nusinersen, an extremely expensive biologic drug (around 100,000 US$ per dose) that needs to be administered intrathecally, is approved for the treatment of 5q-spinal muscular atrophy (SMA). Because of the low muscle tone of the back muscles of pediatric SMA patients, especially type 1 SMA patients, the safe, effective, and fast execution of sheath injection is needed. Therefore, a modified intrathecal injection method was developed accordingly. This paper aims to describe the applicability and safety of this modified method. The modified intrathecal injection method (MIIM) mainly includes a septal needle-free closed infusion connector between the lumbar puncture needle and the syringe, besides the procedures of routine lumbar puncture. Its applicability and safety were evaluated through clinical observation. A total of 92 children with SMA have successfully received nusinersen treatment at our hospital using the modified method since 2019 without obvious adverse events related to the modified injection method. Based on the clinical feedback of operators, the advantages of the modified method include successfully injecting the total dose of nusinersen with constant injection rate and a more stable fixation of the puncture needle, as well as making the operator more relaxed. However, compared with the routine method, the procedure of the modified method has additional steps. The modified intrathecal injection method is an effective and safe method to inject nusinersen when weighing the pros and cons, and it may also be used for administering intrathecal injections of other expensive medicines or for patients with other strict requirements for intrathecal injection.

Preliminary insights into RNA in CSF of pediatric SMA patients after 6 months of nusinersen

BackgroundSpinal muscular atrophy (SMA) is a rare autosomal-recessive neurodegenerative disorder caused by mutations in survival motor neuron 1 (SMN1) gene, and consequent loss of function of SMN protein, which results in progressive loss of lower motor neurons, and muscular wasting. Antisense oligonucleotide (ASO) nusinersen (Spinraza®) modulates the pre–mRNA splicing of the SMN2 gene, allowing rebalance of biologically active SMN. It is administered intrathecally via lumbar puncture after removing an equal amount of cerebrospinal fluid (CSF). Its effect was proven beneficial and approved since 2017 for SMA treatment. Given the direct effect of nusinersen on RNA metabolism, the aim of this project was to evaluate cell-free RNA (cfRNA) in CSF of SMA patients under ASOs treatment for biomarker discovery.MethodsBy RNA-sequencing approach, RNA obtained from CSF of pediatric SMA type 2 and 3 patients was processed after 6 months of nusinersen treatment, at fifth intrathecal injection (T6), and compared to baseline (T0).ResultsWe observed the deregulation of cfRNAs in patients at T6 and we were able to classify these RNAs into disease specific, treatment specific and treatment dependent. Moreover, we subdivided patients into “homogeneous” and “heterogeneous” according to their gene expression pattern. The “heterogeneous” group showed peculiar activation of genes coding for ribosomal components, meaning that in these patients a different molecular effect of nusinersen is observable, even if this specific molecular response was not referable to a clinical pattern.ConclusionsThis study provides preliminary insights into modulation of gene expression dependent on nusinersen treatment and lays the foundation for biomarkers discovery.

Closing the Gap - Detection of 5q-Spinal Muscular Atrophy by Short-Read Next-Generation Sequencing and Unexpected Results in a Diagnostic Patient Cohort.

The importance of early diagnosis of 5q-Spinal muscular atrophy (5q-SMA) has heightened as early intervention can significantly improve clinical outcomes. In 96% of cases, 5q-SMA is caused by a homozygous deletion of SMN1. Around 4 % of patients carry a SMN1 deletion and a single-nucleotide variant (SNV) on the other allele. Traditionally, diagnosis is based on multiplex ligation probe amplification (MLPA) to detect homozygous or heterozygous exon 7 deletions in SMN1. Due to high homologies within the SMN1/SMN2 locus, sequence analysis to identify SNVs of the SMN1 gene is unreliable by standard Sanger or short-read next-generation sequencing (srNGS) methods. The objective was to overcome the limitations in high-throughput srNGS with the aim of providing SMA patients with a fast and reliable diagnosis to enable their timely therapy. A bioinformatics workflow to detect homozygous SMN1 deletions and SMN1 SNVs on srNGS analysis was applied to diagnostic whole exome and panel testing for suggested neuromuscular disorders (1684 patients) and to fetal samples in prenatal diagnostics (260 patients). SNVs were detected by aligning sequencing reads from SMN1 and SMN2 to an SMN1 reference sequence. Homozygous SMN1 deletions were identified by filtering sequence reads for the ,, gene-determining variant" (GDV). 10 patients were diagnosed with 5q-SMA based on (i) SMN1 deletion and hemizygous SNV (2 patients), (ii) homozygous SMN1 deletion (6 patients), and (iii) compound heterozygous SNVs in SMN1 (2 patients). Applying our workflow in srNGS-based panel and whole exome sequencing (WES) is crucial in a clinical laboratory, as otherwise patients with an atypical clinical presentation initially not suspected to suffer from SMA remain undiagnosed.

Registry of Patients with Spinal Muscular Atrophy in a Tertiary Care Unit in Egypt

Background Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Objectives To register patients with SMA who are diagnosed clinically and genetically (typical and atypical forms) in a tertiary care unit in Egypt. Patient and methods 80 Patients with SMA who are diagnosed clinically and genetically at Neuromuscular Unit of Ain Shams University Hospital were registered. Demographical data and genetics of the patients were collected and analyzed. The patients were assessed for skeletal deformities, cardiac evaluation by echo and pulmonary evaluation by PFTs (for patients above 5 years old) and functional assessment by motor scales according to age and type of each patient was done. Results SMA was more common in males with predominance of type II and median age of 4.5 years old, a considerable number of cases had positive history of consanguinity and similar cases in family, 98.8% of cases had the typical form of SMA with homozygous deletion of SMN1 gene with variable SMN2 copy number according to type. 32.5% of cases had skeletal deformities in the form of scoliosis with or without kyphosis, extremities contractures and chest cave deformities. 4 cases had restrictive pattern due to scoliosis cardiac abnormalities were detected in 3 cases of type I. 31 cases were assessed by CHOP INTEND and 49 cases were assessed by HFMSE giving a good tool for assessing disease progress and role of physiotherapy. Severe chest infection and respiratory failure was the cause of death of 3 cases of type I during the period of study. Conclusion registry of SMA patients will lead to a better understanding of the natural history of SMA and the influence of drug treatment. This is crucial to improve the care of SMA patients.

A Family-based Association Test of the VDR Gene in Proximal Spinal Muscular Atrophy

Different factors may be involved in the clinical heterogeneity of spinal muscular atrophy disease. The vitamin D receptor (VDR) might be a candidate gene for this disease. Our study aimed to assess the preferential transmission of VDR polymorphisms from parents to SMA children. We genotyped 261 subjects (87 SMA nuclear families) for VDR FokI, BsmI, ApaI, and TaqI polymorphisms. The transmission of the genetic marker was estimated with Plink and FBAT software. It detected a preferential transmission of the rs731236 and rs7975232 variants to SMA1 patients and of rs1544410 variants to SMA2 patients. The variants of rs2228570 were preferentially transmitted to parents of all SMA patients. Haplotype analysis identified that haplotypes C-C-G-A and T-A-A-G seem to be involved in the booth type of SMA whereas the impact of T-A-A-A seems to be limited only to SMA2. Strong linkage disequilibrium (LD) between rs7975232 and rs1544410 was detected in samples from parents. Even though we investigated a small number of nuclear families the results suggest a potential link between VDR polymorphisms and SMA disease.

Evaluating the performance of four assays for carrier screening of spinal muscular atrophy

Background and aimsSpinal muscular atrophy (SMA) is an autosomal recessive inherited neuromuscular condition caused by biallelic mutations in the survival of motor neuron 1 (SMN1) gene. A homozygous deletion of the SMN1 gene accounts for approximately 95–98% of SMA patients. A highly homologous gene survival motor neuron 2 (SMN2) can partially compensate for SMN1 deletion, and its copy number is associated with disease severity. Population-based carrier screening by simultaneous quantification of SMN1 and SMN2 copy numbers is the best method to prevent SMA. Materials and methodsIn this study, a total of 516 samples were re-tested for the SMN1 copy number by using quantitative polymerase chain reaction (qPCR), multiplex ligation probe amplification (MLPA), droplet digital PCR (ddPCR), high-resolution melting (HRM) analysis, and PCR-based capillary electrophoresis (PCR/CE) simultaneously. Then, the performance of these methods was compared by using MLPA results as the reference. ResultsThe results of qPCR, ddPCR, HRM, and PCR/CE in detecting heterozygous deletion of SMN1 exon 7 and the results of ddPCR, HRM, and PCR/CE in detecting ≥2 copies of SMN1 exon7 are totally consistent with those of MLPA. The sensitivity and specificity of qPCR for detection of 2 copies of SMN1 exon 7 were 99.7% and 98.8%, respectively. The sensitivity and specificity of qPCR for detection of >2 copies of SMN1 exon 7 were 96.3% and 99.8%, respectively. Compared with the MLPA results, the sensitivity and specificity of qPCR and HRM for detection of heterozygous deletion of SMN1 exon 8 were 100% and 100%, respectively. They were 99.4% and 100%, respectively for detection of 2 copies, and 100% and 100%, respectively for detection of >2 copies. The results of PCR/CE in detecting SMN1 exon 8 were consistent with those of MLPA. ConclusionAll these four methods show excellent performance in detecting heterozygous deletion of SMN1 exon 7. All PCR/CE results are totally concordant with those of MLPA. As the most cost-effective method, qPCR also shows high sensitivity and specificity in detecting SMN1. Taken together, our study provides useful information to select appropriate methods for SMA carrier screening.

Caregivers' Expectations on Possible Functional Changes following Disease-Modifying Treatment in Type II and III Spinal Muscular Atrophy: A Comparative Study.

Background: The primary aim of this study was to explore current caregivers' expectations on possible functional changes following treatment in comparison to data obtained in the pre-pharmacological era. Methods: A questionnaire, previously used in 2016, was administered to caregivers of type II and III SMA patients of age between 3 and 71 years, and to patients over the age of 13 years. The questionnaire focuses on (1) caregivers and patients expectations, (2) meaningfulness of the changes observed on the functional motor scales, and (3) their willingness to be enrolled in a clinical trial. A comparative study was performed with data obtained using the same questionnaire soon before the advent of disease-modifying therapies. Results: We administered the questionnaire to 150 caregivers. When comparing current caregiver data to those obtained in 2016, the most obvious differences were related to disease perception over the last year (stability: 16.5% in 2016 vs. 43.6% in 2022; deterioration 70.5% vs. 12.8%, and improvement: 12.9% vs. 43.6%) and expectations from clinical trials with higher expectations in 2022 compared to 2016 (p < 0.001). Forty-five of the 150 in the current study were caregivers of patients above the age of 13. In these 45 the questionnaire was also administered to the patient. No difference was found in responses between patients and their caregivers. Conclusions: Both carers and patients reported that even small changes on functional scales, similar to those reported by clinical studies and real-world data, are perceived as meaningful. Comparing the recent responses to those obtained in 2016, before pharmacological treatment was available, we found significant changes in caregivers' perception with increased expectations. These findings will provide a better understanding of the patients' expectations and facilitate discussion with regulators.

CO41 Real-World Outcomes of Nusinersen or Onasemnogene Abeparvovec (OA) Monotherapy, or Switching to OA from Nusinersen in SMA Patients Aged ≥6 Months

CO41 Real-World Outcomes of Nusinersen or Onasemnogene Abeparvovec (OA) Monotherapy, or Switching to OA from Nusinersen in SMA Patients Aged ≥6 Months

N°207 – Evaluation of motor unit number with MScanFit in SMA and ALS patients at diagnosis and one year after the treatment with nusinersen and riluzole respectively

N°207 – Evaluation of motor unit number with MScanFit in SMA and ALS patients at diagnosis and one year after the treatment with nusinersen and riluzole respectively

Cervical Spinal Cord Gray Matter Area is Associated with Motor Unit Number Index in Spinal Muscular Atrophy (S33.008)

<h3>Objective:</h3> To evaluate the association between spinal cord (SC) gray matter (GM) atrophy and Motor Unit Number Index (MUNIX) in patients with 5q-Spinal Muscular Atrophy (SMA). <h3>Background:</h3> There is an unmet need for valid imaging markers to monitor the disease course and therapeutic outcome in SMA. The novel rAMIRA (radially sampled Averaged Magnetization Inversion Recovery Acquisitions) method enables high in-plane resolution MR-imaging with improved contrast of SC GM in clinically feasible acquisition times. MUNIX is an established quantitative neurophysiological measure that provides an index of the number of functioning lower motor neurons that supply a muscle. The association between SC GM area and MUNIX has not been investigated in SMA yet. <h3>Design/Methods:</h3> Using axial 2D rAMIRA imaging, we prospectively investigated 21 patients with 5q-SMA, types 2 and 3 (mean age/SD 41.3/11.6y, 9 women) and 21 age- and sex-matched healthy controls (HC) (mean age/SD 41.7/11.4y, 9 women) at the intervertebral disc level C5/C6 perpendicular to the spinal cord. SC GM areas were determined using a semi-automated approach. MUNIX of the biceps brachii (BB) was measured following the ENCALS protocol. The association between SC GM area and MUNIX was assessed using multivariable regression analysis covarying for age and sex. <h3>Results:</h3> SC GM area at C5/6 was significantly reduced in patients compared to HC (mean GM area in mm² (SD): SMA 17.5 (2.2); HC 21.1 (2.3); relative reduction: 17.1% (p&lt;0.0001)). In multivariable regression analysis SC GM area at C5/6 explained 53% of MUNIX variance of the BB in SMA patients. <h3>Conclusions:</h3> In patients with SMA, SC GM area is strongly associated with motor neuron function quantitated by MUNIX in the corresponding myotome, indicating the functional relevance of this structural marker. Further longitudinal studies are necessary to evaluate the potential of this novel imaging marker for monitoring the disease course and therapeutic outcome. <b>Disclosure:</b> Dr. Wendebourg has nothing to disclose. Dr. Kesenheimer has nothing to disclose. An immediate family member of Dr. Weidensteiner has received personal compensation for serving as an employee of Siemens Healthineers. Dr. Sander has nothing to disclose. The institution of Matthias Weigel, PhD has received research support from Biogen. Matthias Weigel, PhD has received intellectual property interests from a discovery or technology relating to health care. Tanja Haas has nothing to disclose. The institution of Dirk Fischer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hoffmann La Roche AG. The institution of Dirk Fischer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann La Roche AG. Christoph Neuwirth has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen USA. Christoph Neuwirth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen Switzerland. Nathalie Braun has nothing to disclose. Dr. Weber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen Idec. Dr. Weber has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Granziera has nothing to disclose. Prof. Sinnreich has nothing to disclose. The institution of Oliver Bieri has received research support from Swiss National Science Foundation. The institution of Oliver Bieri has received research support from MIAC Foundation. The institution of Oliver Bieri has received research support from Biogen. Oliver Bieri has received intellectual property interests from a discovery or technology relating to health care. Regina Schlaeger has nothing to disclose.

Single Center Experience of Nusinersen and Risdiplam in Adult SMA patients (P2-8.015)

<h3>Objective:</h3> We aim to understand the benefits between two therapies in adults and potential adverse events. <h3>Background:</h3> Spinal Muscular Atrophy is an autosomal recessive disorder causing progressive degeneration of anterior horn cell resulting in muscle weakness. This is due to mutation in SMN1 gene. SMA is phenotypically classified into 5 types based on age at onset of symptoms. Current approved therapies for adults include antisense oligonucleotide-Nusinersen and a small molecule mRNA splicing modifier-Risdiplam. <h3>Design/Methods:</h3> 15 adult SMA patient who are on treatment with either Nusinersen or Risdiplam were reviewed and RULM score, treatment adverse effect data were collected. <h3>Results:</h3> We reviewed a total of 15 adult SMA patients. The mean age was 44.6 years (30–64) and 10 were female. 10 had 3 copies, 3 had 4 copies and 1 had 2 copies of SMN2 gene. 12 patients received Nusinersen out of which 7 switched to Risdiplam. The RULM scoring that was performed at each of their clinic visit were collected for pre and post treatment from 2018 to 2022. On Nusinersen 7/12 (58.3%, <i>p-value 0.003</i>) showed increase in their scores while 2/12 (16.6%) showed decrease and 3/12 (25%) showed no change. Most improvement was observed in fine motor category. On Risdiplam 1/7 (14.2%) showed increase and 4/7 (57.1%) showed decrease in scores and 2/7 (28.5%) were stable. There were no serious adverse events related to intrathecal administration of Nusinersen and were switched to Risdiplam due to patient preference or no improvement in scores. Only one patient discontinued Risdiplam due to significant GI side effects. <h3>Conclusions:</h3> In our single center experience Nusinersen was seen to have better functional outcome RULM scores in comparison to Risdiplam. This however is subject to limited number of patients on Risdiplam and phenotypic variability in patients. There were no serious adverse effects in either of the medications. <b>Disclosure:</b> Dr. Shivaprasad has nothing to disclose. Dr. Benitez has nothing to disclose. Dr. Yari has nothing to disclose. Dr. Anderson has nothing to disclose. Dr. Shroff has received personal compensation for serving as an employee of Alnylam. Dr. Shroff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam.