INTRODUCTION/AIMS:Dissociation of echogenicity of the flexor digitorum profundus (FDP) and flexor carpi ulnaris (FCU) on neuromuscular ultrasound has been reported to be a useful sign to differentiate inclusion body myositis (IBM) from more common disease mimics, but it is not clear that this finding is pathognomonic of IBM. Our study aimed to evaluate whether this sign may be present in certain muscular dystrophies. METHODS:This case series included 6 genetically confirmed muscular dystrophy patients (2 Becker muscular dystrophy [BMD], 2 myotonic dystrophy type 2 [DM2], 1 myotonic dystrophy type 1 [DM1], and 1 facioscapulohumeral muscular dystrophy type 1 [FSHD1]), whose clinical picture was notable for selective deep finger flexor weakness. Neuromuscular ultrasound had been used to image the proximal medial forearm, where echointensity (EI) of the FDP and FCU was visually graded according to the Heckmatt scale and an FDP/FCU EI ratio was generated from quantitative grayscale analysis. RESULTS:The FDP had a higher EI-by Heckmatt grade and quantitative grayscale-than the FCU in all 6 patients, indicating preferential ultrasonographic involvement of the FDP in these muscular dystrophy cases. DISCUSSION:Ultrasonographic FDP-FCU dissociation of echogenicity confirms selective deep finger flexor involvement. The differential diagnosis of this imaging sign includes IBM but also certain muscular dystrophies (BMD, DM1, DM2, and FSHD), which should be considered in uncommon presentations of suspected IBM or when additional supportive diagnostic findings thereof are lacking.

Introduction: Autologous CD19 CART therapies have been utilized across a wide range of B cell driven autoimmune diseases (AD), including systemic lupus erythematous (SLE), idiopathic inflammatory myopathies (IIM), systemic sclerosis (SSc), & myasthenia gravis (MG). To date, a number of autologous CD19-CART therapies have delivered durable drug free responses in AD patients. However, the safety profile of autologous CD19-CART therapies across different AD has yet to be fully explored. This is especially true for CRS & ICANS. Here, we provide novel insight into the mechanism underlying the safety profile of resecabtagene autoleucel (rese-cel) an autologous CD19 41BBz CART therapy across four separate Phase I/II clinical trials in SLE, IIM, SSc, & MG. Objectives: The primary objective of each trial is safety & tolerability of rese-cel at Day 29. Key secondary objectives include changes in clinical scores & use of immunomodulatory agents. Key translational assessments include CART cell pharmacokinetics (PK), impact on peripheral B cell populations (pharmacodynamics), & serum cytokine levels. Methods: 19 Patients (data cutoff: 6/2/2025 SLE; 5/6/2025 IIM, SSc, and MG), with active disease refractory to standard of care have been treated across 4 Phase I/II clinical trials in SLE (8 patients; NCT06121297), IIM (8 patients; NCT06154252), SSc (2 patients; NCT06328777), & MG (1 patient; NCT06359041). All patients were treated with a single weight-based infusion of rese-cel at a dose of 1 x 106 cells/kg following lymphodepletion (flu 25 mg/m2/d on Days -5, -4, & -3, & cy 1,000 mg/m2/d on Day -3). All non-glucocorticoid immunomodulatory agents were stopped prior to lymphodepletion. Glucocorticoids were tapered post-infusion. Patients were not given prophylactic tocilizumab pre-infusion. Translational assessments were determined as follows: CART PK was evaluated by flow cytometry & dPCR; B-cell enumeration & phenotyping were evaluated by flow cytometry; & serum cytokines were evaluated via immunoassay. Results: Across all indications (19 patients), 7 episodes of CRS were observed (7/19). 6 of 7 patients experienced a Grade 1 CRS, & 1 patient had a Grade 2 CRS. 2 patients developed ICANS; 1 patient had a Grade 4 (previously presented at ACR Convergence 2024), & the other patient had a Grade 3. Both ICANS events were rapidly resolved without sequelae using standard therapy. These CRS and ICANS events differed across indications. In IIM, 4 of 8 patients experienced Grade 1 CRS and no patients experienced ICANs. In SLE, 2 patients experienced Grade 1 CRS and one developed Grade 4 ICANs. In SSC, 1 of 2 patients experienced Grade 2 CRS & the other experienced Grade 3 ICANS. In MG, no CRS or ICANS was observed. Rese-cel infusion products were ~ 66% transduced, with a mean CD4:CD8 ratio of 6. Post-infusion, peak CART expansion was observed on day 12 & the mean peak expansion was 89 cells/µL (SD +/- 214). B cells were rapidly depleted from peripheral blood post-infusion, with nadir occurring at 13 days & repopulation beginning at 62 days post-infusion on average. Re-emergent B cells were largely of the CD24+CD38+ transitional naïve phenotype. Commensurate with B cell depletion, serum BAFF induction was observed, with a mean fold induction of 16 & mean peak level of 56,404 pg/µL (SD: +/- 45,547). Serum cytokines associated with CRS & ICANS; IFNg, IL6, & IL8 reached peak elevation on days 10, 9, & 10 respectively post-infusion. The mean peak elevation for IFNg, IL6, & IL8 were 232 pg/ µL (SD: +/- 320), 44 pg/ µL (SD: +/- 60), & 80 pg/ µL (SD +/- 73), respectively. Conclusion: Rese-cel appears to be well tolerated in autoimmune patients with rates of CRS & ICANS of 37% & 11% across all autoimmune indications, respectively (SLE patients had a 25% CRS rate & 12.5% ICANS rate, IIM patients had a 50% CRS rate & 0% ICANS rate, SSC patients had a 50% CRS & 50% ICANS rate, & MG patients had a 0% CRS & ICANS rate). Notably, the frequency & severity of CRS appears to be low, with no CRS in 63% of patients (12/19) & most CRS events (6/7) being Grade 1. The lower frequency & severity of both CRS & ICANS events are likely correlated with the relatively modest induction of serum IFNg, IL6, & IL8 found in autoimmune patients post rese-cel weight-adjusted dose infusion. High BAFF levels reflect deep systemic B cell depletion. Together, these data support further support late-stage clinical development of rese-cel in autoimmune disease.

OBJECTIVE:We report the 12-month follow-up outcomes from a Phase 2 clinical trial (NCT04146051) evaluating Descartes-08, a BCMA-directed RNA chimeric antigen receptor T-cell (rCAR-T) therapy for refractory generalized myasthenia gravis (MG). These findings provide insight into the potential applicability of BCMA-targeted rCAR-T therapy for antibody-mediated autoimmune diseases. METHODS:In the Phase 2a part of the study, Descartes-08 was administered at 52.5 × 106 CAR+ cells/kg per infusion with varying dosing frequencies as an outpatient treatment and without lymphodepletion chemotherapy. A subset of participants received Descartes-08 as six weekly infusions and were followed long term with assessments conducted at 2, 3, 6, 9, and 12 months. RESULTS:All seven participants who received six weekly infusions of Descartes-08 exhibited clinically meaningful improvement in common MG severity scales (MG Composite, MG Activities of Daily Living, Quantitative MG scores, and Quality of Life 15-revised) at Month 3 without significant toxicity. At Month 9 follow-up, all participants continued to experience marked clinically meaningful improvements. Five out of seven participants maintained the response at Month 12. A third participant experienced a relapse approximately 6 months after completing on-study follow-up. All three participants who experienced loss of clinical effects were retreated. Two had rapid improvement in clinical scores with minimal symptom expression at Week 8, which was maintained through 12 months of retreatment follow-up. The third participant experienced similar improvement in MG severity scores to their initial treatment. INTERPRETATION:These data support continued development of Descartes-08 in myasthenia gravis and other autoantibody-associated autoimmune disorders.

BACKGROUND:Immune-mediated necrotizing myopathy (IMNM) and dermatomyositis (DM) are characterized by weakness, hyperCKemia, associated autoantibodies, and varying extramuscular manifestations. Muscle MRI, currently subordinate to histopathology and serology in idiopathic inflammatory myopathy (IIM) classification, has an evolving role. Our study aims to define thigh muscle MRI involvement in IMNM and DM by direct comparison. METHODS:This single-center, retrospective, cross-sectional study included 25 participants, who met IIM classification criteria (14 IMNM, 11 DM) and had available thigh MRI. Clinical and paraclinical data were available and reviewed. 11 muscles were graded for edema on MRI using a semi-quantitative scale (0: normal, 1: <30% of muscle involvement, 2: 31-75%, 3: > 75%). For 3 participants with no significant muscle edema, muscle fatty infiltration was scored according to the same scale. Using linear mixed-effects models, muscle scores were compared between the two groups and a secondary analysis was performed of only edema scores, excluding the 3 participants with fatty infiltration scores. RESULTS:The most affected muscles in IMNM were the semimembranosus (3.0 [2.7-3.0] {median [IQR]}), biceps femoris-long head (BF-LH) (2.7 [2.0-3.0]), and adductors (2.5 [2.0-3.0]). In DM, the most affected muscles were the vastus lateralis (2.7 [2.3-3.0]), vastus intermedius (2.9 [2.2-3.0]), vastus medialis (2.3 [1.7-2.7]), semitendinosus (2.2 [1.0-2.7]), rectus femoris (RF) (2.0 [1.0-2.8]), biceps femoris-short head (BF-SH) (1.9 [1.0-2.7]), gracilis, and sartorius. Intergroup statistical difference of scores was significant (p < 0.01) for 10/11 thigh muscles excluding the RF (p = 0.19), supporting an inverse relationship of muscle involvement for DM and IMNM. The secondary comparative analysis of only muscle edema scores was significant (p < 0.05) for the same 10/11 muscles with a consistent direction for all comparisons. CONCLUSION:DM and IMNM affect disparate thigh muscles on MRI. DM preferentially affects the anterior thigh, semitendinosus and BF-SH in the posterior thigh, and gracilis in the medial thigh, whereas IMNM preferentially affects the posterior thigh (semimembranosus and BF-LH) and adductors in the medial thigh.

Treatment options for amyotrophic lateral sclerosis (ALS) remain suboptimal. Results from a phase 2 study of reldesemtiv in ALS suggested that it may slow disease progression. To assess the effect of reldesemtiv vs placebo on functional outcomes in ALS. A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (COURAGE-ALS) was a double-blind, placebo-controlled phase 3 randomized clinical trial conducted at 83 ALS centers in 16 countries from August 2021 to July 2023. The first 24-week period was placebo controlled vs reldesemtiv. All participants received reldesemtiv during the second 24-week period with a 4-week follow-up. Two interim analyses were planned, the first for futility and the second for futility and possible resizing. This was a hybrid decentralized trial with approximately half the trial visits performed remotely and the remaining visits in the clinic. Eligible participants met criteria for definite, probable, or possible ALS with lower motor neuron signs by modified El Escorial Criteria, ALS symptoms for 24 months or less, ALS Functional Rating Scale–Revised (ALSFRS-R) total score of 44 or less, and forced vital capacity of greater than or equal to 65% of predicted. Oral reldesemtiv, 300 mg, or placebo twice daily. The primary end point was change in ALSFRS-R total score from baseline to week 24. Of the 696 participants screened, 207 were screen failures. A total of 486 participants (mean [SD] age, 59.4 [10.9] years; 309 male [63.6%]) were randomized to reldesemtiv (n = 325) or placebo (n = 161); 3 randomized patients were not dosed. The second interim analysis at 24 weeks after randomization included 256 participants. The data monitoring committee recommended that the trial should end due to futility, and the sponsor agreed. The mean (SE) group difference in the ALSFRS-R score from baseline to week 24 was −1.1 (0.53; 95% CI, −2.17 to −0.08; P = .04, favoring placebo). Given excess missing data from early termination, the combined assessment assumed greater importance; it, too, failed to show a benefit from treatment with reldesemtiv (win probability was 0.44 for reldesemtiv and 0.49 for placebo, with a win ratio of 0.91; 95% CI of win ratio, 0.77-1.10; P = .11). This randomized clinical trial failed to demonstrate efficacy for reldesemtiv in slowing functional decline in ALS. ClinicalTrials.gov Identifier: NCT04944784

Anti-NT5c1A antibodies, directed against cytosolic 5’-nucleotidase that is abundant in skeletal muscle, were identified as the first serological biomarker for IBM. Prior research suggested that NT5c1A seropositivity prognosticated a more severe motor phenotype with more severe motor weakness and bulbar involvement. Subsequent studies produced conflicting data, either confirming previous observations or not showing any relationship. The debate remains whether serological status may provide insight into functional severity and disease behavior. INSPIRE-IBM is a prospective NIH-funded observational study including patients ages 40 years or older with clinically defined IBM fulfilled by the ENMC 2011 criteria, and disease onset within the past 10 years of the Baseline visit. Serology for NT5c1A was collected at Baseline. Functional assessments to evaluate disease severity included Manual Muscle Testing (MMT), Timed get up-and-go (TUG), Sydney Swallow Questionnaire (SSQ), and EAT-10. Serological status was available for 140 out of 150 participants with IBM who were enrolled. Sixty-nine of the 140 IBM patients (49%) were seropositive for NT5c1A antibodies at Baseline. Patients were divided into two groups (Group A with disease duration between 0-5 years and Group B with disease duration between 6-10 years). Seropositive group A showed significantly greater difficulty swallowing (EAT-10 and SSQ) than seronegative group A. Seropositive group B showed a trend towards more difficulty swallowing (EAT-10 and SSQ) and motor function weakness (MMT) compared to the seronegative group but did not reach statistical significance. Seropositive IBM patients appear to have more swallowing difficulties than seronegative patients, and this difference appears early on in the disease course.

Becker muscular dystrophy (BMD) is a progressive disorder and impairs upper extremity (UE) function. The Performance of Upper Limb (PUL) measures UE function in muscular dystrophy, but has a ceiling effect in high-functioning subjects. Yet, fat fraction (FF) values via quantitative magnetic resonance (qMRI) have been used as biomarkers of muscle deterioration. Thus, the study aims to 1) determine if the PUL or qMRI FF can discriminate between functional groups of men with BMD and controls, and 2) assess relationships between PUL scores and qMRI FF. In a cross-sectional study, 56 men with BMD and 9 controls (18-63 yrs) completed PUL 2.0 and whole-body qMRI. Composite FF values for UE (deltoid, biceps & triceps) and whole-body were calculated. To understand the impact of mobility on UE performance, men with BMD were grouped using the 10-m run/walk test. Functional groups were: A) non-ambulatory B) walks – with no increase in speed possible; C) fast walking or jog; or D) run. One-way ANOVA/Kruskal-Wallis and Spearman's rho were used to assess differences between groups and correlations, respectively. Men with BMD scored 18-42 on the PUL. The PUL only detects differences between non-ambulatory (Group A) and high-functioning (Group C: p<0.001; Group D: p=0.02; Controls: p<0.001) groups. However, qMRI UE FF composite can discriminate between low-functioning (Groups A-B) and high-functioning (Groups C-D) men with BMD and whole-body FF composite can discriminate between all BMD functional groups (p<0.001 to 0.02). Higher PUL scores were associated with lower qMRI FF (p<0.05; rho =-0.70 to -0.50) only in low-functioning men with BMD (Groups A&B). Thus, the PUL has utility in assessing UE function in low-functioning men with BMD. Because the PUL may provide limited information about UE impairment in high-functioning men with BMD, it should be used cautiously or together with other biomarkers such as qMRI FF.

A patient in their 60s developed gradual-onset, painless weakness of the left ankle associated with numbness involving the lateral aspect of the left foot. Toe walking was difficult, and imbalance contributed to several falls. Neurological examination was notable for left-sided ankle plantarflexion

Inclusion body myositis (IBM) is a common muscular disorder in individuals over the age of 40 years, characterized by atrophy and progressive muscle weakness. Patient-reported outcomes such as the IBMFRS or the sIFA questionnaire provide valuable insights into disease impact from the patient's perspective on their symptoms, functional limitations, and quality of life. However, it remains a topic of further investigation to determine which of these questionnaires exhibits stronger correlations with disease progression. The INSPIRE-IBM is a natural history study involving 150 IBM patients across 13 different US sites. Evaluations are conducted biannually over two years and patients complete IBMFRS, sIFA, EAT-10, Sydney Swallow Questionnaire, PROMIS, along with manual muscle testing and pulmonary functions tests. This abstract analyzes correlations between IBMFRS and sIFA with the other assessments by regression analysis to identify which is a stronger correlator with disease progression. Preliminary analysis, involving 87 patients who completed three time points, revealed a strong correlation between IBMFRS and sIFA (R2=0.7, p=3.21E-96). Both outcomes show moderate correlation with PFTs (R2 between 0.5-0.7), with no significant difference in strength of correlation. IBMFRS and sIFA exhibit similar correlation with MMTs (R2=0.43, p=0.93). As the study is ongoing, more timepoints will be available per patient closer to the conference date and will be included in the analysis.

Inclusion body myositis is an enigmatic slowly progressive acquired myopathy. There is strong evidence favoring autoimmune origin, including the invasion of non-necrotic myofibers by clonally expanded cytotoxic CD8+ T cells, which have the hallmark of highly and possibly terminally differentiated T cells, expressing the killer cell lectin-like receptor G1 (KLRG1) cell surface ligand, and have features of senescence. Previous research suggests there is greater T cell differentiation with longer disease severity, though there is a paucity of information surrounding how muscle-invading T cells may influence disease behavior. Understanding the frequency of highly differentiated lymphocytes and their relationship to disease severity and behavior may influence novel therapeutic solutions. INSPIRE-IBM is a longitudinal NIH-funded multicenter study including patients ages 40 years or older with clinically defined IBM fulfilled by the ENMC 2011 criteria, and disease onset within the past 10 years of the Baseline visit. Complete dataset for the baseline cross-sectional visit was available from 60 participants. Flow cytometry was used on PBMCs to analyze percentage of immunosenescent lymphocytes staining for CD8+, KRLG1+, TEMRAs, and Tregs. Functional assessments to evaluate disease severity included Manual Muscle Testing (MMT), Timed get up-and-go (TUG), Sydney Swallow Questionnaire (SSQ), and EAT-10. Data will be analyzed in May 2024 and results from Baseline will be presented.

Objective. No clinical trials have been conducted to establish optimal and effective treatment in patients with immune-mediated necrotizing myopathy (IMNM), which can have a refractory course with increased morbidity from permanent muscle damage, especially in patients who experience delay in diagnosis and treatment. A subset of autoimmune necrotizing myopathy is associated with antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Treatment involves withdrawing statins and using a combination of immunosuppressant and immunomodulatory treatment. Our study aims to provide longitudinally collected data on outcomes of early versus late initiation of intravenous Ig (IVIG) using our myositis center cohort of patients with anti-HMGCR IMNM. Methods. We conducted a retrospective chart review of 31 adult patients of the Oregon Health and Science University Myositis Center who were diagnosed with anti-HMGCR IMNM from September 2016 through October 2022 and reviewed physical examination, serologic laboratory data, and their treatment including prednisone reception as well as treatment response at 0 (the evaluation immediately before IVIG initiation), 3, 6, and 12 months on treatment. We divided this cohort into those who received IVIG at or before six months after receiving the diagnosis of anti-HMGCR IMNM and refer this as the cohort with nondelayed treatment, and those who received IVIG after six months following their diagnosis, which we referred to as the cohort with delayed treatment. Diagnosis of anti-HMGCR IMNM was defined as per the 2016 European Neuromuscular Centre criteria as having all three of elevated serum creatine kinase (CK), proximal muscle weakness, and anti-HMGCR antibodies. We evaluated the response to treatment by using a limited total improvement score (TIS) as per 2016 American College of Rheumatology/EULAR myositis response criteria. Results. Among the 31 total patients, 19 were included within the cohort with nondelayed treatment, and 12 within the cohort with delayed treatment. The two cohorts had a comparable amount of time between the onset of symptoms and diagnosis; however, the cohort with delayed treatment had a significantly longer time between diagnosis and IVIG treatment (P < 0.001). At disease onset, cohorts had a comparable serum CK (P > 0.999), but patients with delayed treatment had an expected lower serum CK (P = 0.016) at the 0-month time point. At the 0-month time point, nine of the patients with nondelayed treatment (47%) required the use of a walker or wheelchair, whereas eight of the cohort with delayed treatment (66%) did. Patients who received nondelayed treatment demonstrated significant improvement in manual muscle testing 8 at the 12-month intervals (P < 0.001). Average serum CK values of all patients measured at the 3, 6, and 12 months did not significantly differ between the groups with nondelayed and delayed treatment. TIS improved more in the group with nondelayed treatment than in the group with delayed treatment (P = 0.002 at 3 months, P = 0.019 at 6 months, and P = 0.001 at 12 months). Seven patients in the group with delayed treatment had permanent residual muscle weakness requiring walker or wheelchair use at 12 months, whereas none of the patients in the group with nondelayed treatment did. Conclusion. Though our results have limitations, they contribute to a growing body of evidence that suggests that IVIG may prove to be a valuable addition to an early and aggressive induction regimen in patients afflicted by anti-HMGCRIMNM, particularly those with moderate to severe weakness requiring the use of a wheelchair or walking aids. Delay in IVIG treatment may lead to the development of permanent residual weakness and long-term disability.

Objective No clinical trials have been conducted to establish optimal and effective treatment in patients with immune‐mediated necrotizing myopathy (IMNM), which can have a refractory course with increased morbidity from permanent muscle damage, especially in patients who experience delay in diagnosis and treatment. A subset of autoimmune necrotizing myopathy is associated with antibodies against 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR). Treatment involves withdrawing statins and using a combination of immunosuppressant and immunomodulatory treatment. Our study aims to provide longitudinally collected data on outcomes of early versus late initiation of intravenous Ig (IVIG) using our myositis center cohort of patients with anti‐HMGCR IMNM. Methods We conducted a retrospective chart review of 31 adult patients of the Oregon Health and Science University Myositis Center who were diagnosed with anti‐HMGCR IMNM from September 2016 through October 2022 and reviewed physical examination, serologic laboratory data, and their treatment including prednisone reception as well as treatment response at 0 (the evaluation immediately before IVIG initiation), 3, 6, and 12 months on treatment. We divided this cohort into those who received IVIG at or before six months after receiving the diagnosis of anti‐HMGCR IMNM and refer this as the cohort with nondelayed treatment, and those who received IVIG after six months following their diagnosis, which we referred to as the cohort with delayed treatment. Diagnosis of anti‐HMGCR IMNM was defined as per the 2016 European Neuromuscular Centre criteria as having all three of elevated serum creatine kinase (CK), proximal muscle weakness, and anti‐HMGCR antibodies. We evaluated the response to treatment by using a limited total improvement score (TIS) as per 2016 American College of Rheumatology/EULAR myositis response criteria. Results Among the 31 total patients, 19 were included within the cohort with nondelayed treatment, and 12 within the cohort with delayed treatment. The two cohorts had a comparable amount of time between the onset of symptoms and diagnosis; however, the cohort with delayed treatment had a significantly longer time between diagnosis and IVIG treatment ( P < 0.001). At disease onset, cohorts had a comparable serum CK ( P > 0.999), but patients with delayed treatment had an expected lower serum CK ( P = 0.016) at the 0‐month time point. At the 0‐month time point, nine of the patients with nondelayed treatment (47%) required the use of a walker or wheelchair, whereas eight of the cohort with delayed treatment (66%) did. Patients who received nondelayed treatment demonstrated significant improvement in manual muscle testing 8 at the 12‐month intervals ( P < 0.001). Average serum CK values of all patients measured at the 3, 6, and 12 months did not significantly differ between the groups with nondelayed and delayed treatment. TIS improved more in the group with nondelayed treatment than in the group with delayed treatment ( P = 0.002 at 3 months, P = 0.019 at 6 months, and P = 0.001 at 12 months). Seven patients in the group with delayed treatment had permanent residual muscle weakness requiring walker or wheelchair use at 12 months, whereas none of the patients in the group with nondelayed treatment did. Conclusion Though our results have limitations, they contribute to a growing body of evidence that suggests that IVIG may prove to be a valuable addition to an early and aggressive induction regimen in patients afflicted by anti‐HMGCRIMNM, particularly those with moderate to severe weakness requiring the use of a wheelchair or walking aids. Delay in IVIG treatment may lead to the development of permanent residual weakness and long‐term disability.

Becker muscular dystrophy (BMD) results in fat replacement of skeletal muscle and impaired functional performance. Quantitative magnetic resonance (qMR) imaging of muscle fat fraction (FF) has been used as a biomarker of muscle deterioration in muscular dystrophies. Specifically, qMR whole-body imaging (WBI) can quickly analyze multiple muscles and develop FF composites. The North Star Assessment for limb-girdle type muscular dystrophies (NSAD), has the potential to assess motor function in men with BMD across a wide range of abilities. Thus, we aimed to 1) assess the relationship between qMR FF and NSAD scores, and 2) determine qMR FF cut-off values for loss of performance on NSAD tasks that require gluteal and thigh muscle contractions. 41 men with BMD (18-62 years) completed 3-point Dixon qMR WBI and the NSAD. GlutThigh was calculated as the average FF of the right gluteus maximus, gluteus medius/minimus, quadriceps femoris, and hamstrings. The relationship between GlutThigh and function was assessed using Spearman's rho. GlutThigh cut-off values to discriminate men able or unable to perform each NSAD task were calculated using the receiver operating characteristic (ROC) and the Youden Index. Men with BMD had GlutThigh values from 0.08-0.89 (median: 0.58). Higher GlutThigh was strongly associated with lower NSAD scores (rho=-0.93; p<0.001). GlutThigh cut-off values ranged from 0.27 for rise from squat and running to 0.82 for standing and showed 83-100% sensitivity and 67-100% specificity. In men with BMD, higher GlutThigh values are strongly associated with poorer NSAD performance and more challenging NSAD tasks have lower GlutThigh cut-offs. GlutThigh cut-off values have high sensitivity and specificity to detect NSAD task failures across a wide range of men with BMD. Thus, qMR WBI GlutThigh provides important insight into functional performance in men with BMD and may serve as a functionally relevant biomarker of disease status in future clinical trials.

We report the 12-month follow-up results of a phase 2 clinical of Descartes-08 ([NCT04146051][1]), BCMA-directed RNA chimeric antigen receptor T-cell (rCAR-T) therapy for myasthenia gravis (MG) given as an outpatient treatment without lymphodepletion. In the Phase 2a part of the study, all 7 participants who received six weekly infusions of Descartes-08 exhibited clinically meaningful improvement in common MG severity scales (MG Composite, MG Activities of Daily Living, Quantitative MG scores, and Quality of Life 15-revised) at Month 3. At Month 9 follow-up, all participants continued to experience marked clinical improvements. Five out of seven participants maintained clinical improvement at Month 12. Of the two participants who experienced loss of clinical effect at Month 12 and were eligible for retreatment, one was retreated and had rapid improvement in clinical scores with minimal symptom expression which was ongoing at Month 6 of follow-up. All three participants with detectable anti-acetylcholine receptor (AChR) antibody levels at baseline experienced autoantibody reductions by Month 6, which deepened further by Month 9, and were maintained at Month 12. These data support continued development of Descartes-08 in myasthenia gravis and other autoantibody-associated autoimmune disorders. ### Competing Interest Statement G Sahagian has received research support from Cartesian Therapeutic, Inc., Immunovant, and argenx paid to his institution; consulting fees from UCB pharma and Immunovant; honoraria from argenx and Alexion, and travel support from argenx and Immunovant; he also has unpaid positions at MGFCA and AANEM. M Feinberg has received honoraria as a consultant or advisory board member from argenx. CM Jewell has an equity position in Barinthus Biotherapeutics. CM Jewell, M Kurtoglu, and MD Miljkovic are employees of and have ownership interest in Cartesian Therapeutics, Inc. CM Jewell is appointed as an employee of the University of Maryland and VA Maryland Health Care System. The views in this paper do not reflect the views of the state of Maryland or the US Government. MD Miljkovic is appointed as an employee of the University of Maryland Baltimore County. The views in this paper do not reflect the views of the state of Maryland. T Vu is the USF Site Principal Investigator for MG clinical trials sponsored by Alexion/AstraZeneca, argenx, Ra/UCB, Horizon/Viela Bio, Janssen/Momenta, Immunovant, Regeneron, Dianthus, and Cartesian Therapeutics, and receives speaking and/or consulting honoraria relating to MG from Alexion, argenx, and UCB. T Mozaffar has received research support (paid to his institution) from Alexion Pharmaceuticals, Inc, Amicus, Annji, argenx, Astellas Gene Therapy, Cartesian Therapeutics, ML Bio, Sanofi, Spark Therapeutics, UCB and Valerion; consulting fees from Alexion Pharmaceuticals, Inc, Amicus, Annji, argenx, Audentes/Astellas Gene Therapy, Horizon Therapeutics, Maze Therapeutics, Momenta, Sanofi and UCB; support for attending meetings and/or travel from Sanofi; participation on a DSMB or an advisory board from Srepta, Applied Therapeutics, and the National Institutes of Health. JF Howard, Jr. has received research support (paid to his institution) from Alexion AstraZeneca Rare Disease, argenx, Cartesian Therapeutics, the Centers for Disease Control and Prevention, Myasthenia Gravis Foundation of America, Muscular Dystrophy Association, National Institutes of Health (including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), Patient-Centered Outcomes Research Institute, Ra Pharmaceuticals Inc (now UCB), and Takeda Pharmaceuticals; honoraria from Alexion AstraZeneca Rare Disease, argenx, Biologix Pharma, Immunovant, Inc, Merck EMB Serono, NMD Pharma, Novartis Pharma, Ra Pharmaceuticals Inc (now UCB), Regeneron Pharmaceuticals Inc, Sanofi US, Viela Bio/ Horizon Therapeutics plc, Inc (now Amgen) and Zai Labs; he has also received nonfinancial support from Alexion Pharmaceuticals, Inc, argenx BV, Ra Pharmaceuticals Inc (now UCB), Toleranzia AB and Zai Labs. All other authors declare no competing interests. ### Clinical Trial NCT04146051 ### Funding Statement Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Awards Number R25NS088248 and NS115426-01A1. Study was sponsored by Cartesian Therapeutics, Inc. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: A central Institutional Review Board (Western IRB) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Access to anonymised, individual, and trial-level data (analysis datasets) will be provided by request from qualified researchers performing independent, rigorous research, after review and approval of a research proposal and statistical analysis plan and execution of a data sharing agreement. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04146051&atom=%2Fmedrxiv%2Fearly%2F2024%2F01%2F04%2F2024.01.03.24300770.atom