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Browsing by Author "Goyal, Namita A."
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Item Investigating Late-Onset Pompe Prevalence in Neuromuscular Medicine Academic Practices: The IPaNeMA Study(Wolters Kluwer, 2021-10-18) Wencel, Marie; Shaibani, Aziz; Goyal, Namita A.; Dimachkie, Mazen M.; Trivedi, Jaya; Johnson, Nicholas E.; Gutmann, Laurie; Wicklund, Matthew P.; Bandyopadhay, Sankar; Genge, Angela L.; Freimer, Miriam L.; Goyal, Neelam; Pestronk, Alan; Florence, Julaine; Karam, Chafic; Ralph, Jeffrey W.; Rasheed, Zinah; Hays, Melissa; Hopkins, Steve; Mozaffar, Tahseen; Neurology, School of MedicineBackground and objectives: We investigated the prevalence of late-onset Pompe disease (LOPD) in patients presenting to 13 academic, tertiary neuromuscular practices in the United States and Canada. Methods: All successive patients presenting with proximal muscle weakness or isolated hyperCKemia and/or neck muscle weakness to these 13 centers were invited to participate in the study. Whole blood was tested for acid alpha-glucosidase (GAA) assay through the fluorometric method, and all cases with enzyme levels of ≤10 pmoL/punch/h were reflexed to molecular testing for mutations in the GAA gene. Clinical and demographic information was abstracted from their clinical visit and, along with study data, entered into a purpose-built REDCap database, and analyzed at the University of California, Irvine. Results: GAA enzyme assay results were available on 906 of the 921 participants who consented for the study. LOPD was confirmed in 9 participants (1% prevalence). Another 9 (1%) were determined to have pseudodeficiency of GAA, whereas 19 (1.9%) were found to be heterozygous for a pathogenic GAA mutation (carriers). Of the definite LOPD participants, 8 (89%) were Caucasian and were heterozygous for the common leaky (IVS1) splice site mutation in the GAA gene (c -32-13T>G), with a second mutation that was previously confirmed to be pathogenic. Discussion: The prevalence of LOPD in undiagnosed patients meeting the criteria of proximal muscle weakness, high creatine kinase, and/or neck weakness in academic, tertiary neuromuscular practices in the United States and Canada is estimated to be 1%, with an equal prevalence rate of pseudodeficiency alleles.Item A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of Reldesemtiv In Patients With ALS(Taylor & Francis, 2021-05) Shefner, Jeremy M.; Andrews, Jinsy A.; Genge, Angela; Jackson, Carlayne; Lechtzin, Noah; Miller, Timothy M.; Cockroft, Bettina M.; Meng, Lisa; Wei, Jenny; Wolff, Andrew A.; Malik, Fady I.; Bodkin, Cynthia; Brooks, Benjamin R.; Caress, James; Dionne, Annie; Fee, Dominic; Goutman, Stephen A.; Goyal, Namita A.; Hardiman, Orla; Hayat, Ghazala; Heiman-Patterson, Terry; Heitzman, Daragh; Henderson, Robert D.; Johnston, Wendy; Karam, Chafic; Kiernan, Matthew C.; Kolb, Stephen J.; Korngut, Lawrence; Ladha, Shafeeq; Matte, Genevieve; Mora, Jesus S.; Needham, Merrilee; Oskarsson, Bjorn; Pattee, Gary L.; Pioro, Erik P.; Pulley, Michael; Quan, Dianna; Rezania, Kourosh; Schellenberg, Kerri L.; Schultz, David; Shoesmith, Christen; Simmons, Zachary; Statland, Jeffrey; Sultan, Shumaila; Swenson, Andrea; Van Den Berg, Leonard H.; Vu, Tuan; Vucic, Steve; Weiss, Michael; Whyte-Rayson, Ashley; Wymer, James; Zinman, Lorne; Rudnicki, Stacy A.; Neurology, School of MedicineTo evaluate safety, dose response, and preliminary efficacy of reldesemtiv over 12 weeks in patients with amyotrophic lateral sclerosis (ALS). Methods: Patients (≤2 years since diagnosis) with slow upright vital capacity (SVC) of ≥60% were randomized 1:1:1:1 to reldesemtiv 150, 300, or 450 mg twice daily (bid) or placebo; active treatment was 12 weeks with 4-week follow-up. Primary endpoint was change in percent predicted SVC at 12 weeks; secondary measures included ALS Functional Rating Scale-Revised (ALSFRS-R) and muscle strength mega-score. Results: Patients (N = 458) were enrolled; 85% completed 12-week treatment. The primary analysis failed to reach statistical significance (p = 0.11); secondary endpoints showed no statistically significant effects (ALSFRS-R, p = 0.09; muscle strength mega-score, p = 0.31). Post hoc analyses pooling all active reldesemtiv-treated patients compared against placebo showed trends toward benefit in all endpoints (progression rate for SVC, ALSFRS-R, and muscle strength mega-score (nominal p values of 0.10, 0.01 and 0.20 respectively)). Reldesemtiv was well tolerated, with nausea and fatigue being the most common side effects. A dose-dependent decrease in estimated glomerular filtration rate was noted, and transaminase elevations were seen in approximately 5% of patients. Both hepatic and renal abnormalities trended toward resolution after study drug discontinuation. Conclusions: Although the primary efficacy analysis did not demonstrate statistical significance, there were trends favoring reldesemtiv for all three endpoints, with effect sizes generally regarded as clinically important. Tolerability was good; modest hepatic and renal abnormalities were reversible. The impact of reldesemtiv on patients with ALS should be assessed in a pivotal Phase 3 trial. (ClinicalTrials.gov Identifier: NCT03160898).