Shafeeq Ladha
A5039905544- Amyotrophic Lateral Sclerosis Research
- Lysosomal Storage Disorders Research
- Peripheral Neuropathies and Disorders
- Neurogenetic and Muscular Disorders Research
- Glycogen Storage Diseases and Myoclonus
- Biochemical and Molecular Research
- Hereditary Neurological Disorders
- Child Nutrition and Feeding Issues
- Parkinson's Disease Mechanisms and Treatments
- Myasthenia Gravis and Thymoma
- Autoimmune Neurological Disorders and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Peripheral Nerve Disorders
- Nerve injury and regeneration
- Genetic Neurodegenerative Diseases
- Carbohydrate Chemistry and Synthesis
- Long-Term Effects of COVID-19
- Health Systems, Economic Evaluations, Quality of Life
- Biochemical Acid Research Studies
- Neurological disorders and treatments
- Prion Diseases and Protein Misfolding
- Antifungal resistance and susceptibility
- Alcoholism and Thiamine Deficiency
- Muscle Physiology and Disorders
- biodegradable polymer synthesis and properties
Barrow Neurological Institute
2016-2025
St. Joseph's Hospital and Medical Center
2013-2024
Jeroen Bosch Ziekenhuis
2023
Duke University
2022
Assistance Publique – Hôpitaux de Paris
2022
University of Kansas Medical Center
2016-2022
University of Florida
2016-2022
Inserm
2022
University of Missouri
2022
University Medical Center Utrecht
2022
Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration tofersen being studied for treatment amyotrophic lateral sclerosis (ALS) due mutations.We conducted a phase 1-2 ascending-dose trial evaluating in adults with ALS mutations. In each dose cohort (20, 40, 60, or 100 mg), participants were randomly assigned 3:1 ratio receive five doses placebo, administered...
Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy safety of a combination the two compounds persons with amyotrophic lateral sclerosis (ALS) are not known.
Poly(GP) proteins are a promising pharmacodynamic marker for developing and testing therapeutics treating C9ORF72 -associated amyotrophic lateral sclerosis.
Abstract An orally administered, fixed‐dose coformulation of sodium phenylbutyrate‐taurursodiol (PB‐TURSO) significantly slowed functional decline in a randomized, placebo‐controlled, phase 2 trial ALS (CENTAUR). Herein we report results long‐term survival analysis participants CENTAUR. In CENTAUR, adults with were randomized 2:1 to PB‐TURSO or placebo. Participants completing the 6‐month (24‐week) eligible receive open‐label extension. all‐cause mortality (35‐month maximum follow‐up...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor nervous system. Clinical studies have demonstrated cortical and spinal neuron hyperexcitability using transcranial magnetic stimulation threshold tracking nerve conduction studies, respectively, although metrics excitability not been used as pharmacodynamic biomarkers in multi-site clinical trials.To ascertain whether ezogabine decreases ALS.This double-blind, placebo-controlled phase 2 randomized...
Abstract Objective To investigate neurodegenerative and inflammatory biomarkers in people with amyotrophic lateral sclerosis (PALS), evaluate their predictive value for ALS progression rates, assess utility as pharmacodynamic monitoring treatment effects. Methods De‐identified, longitudinal plasma, cerebrospinal fluid (CSF) samples from PALS ( n = 108; 85 ≥2 visits) controls without neurological disease 41) were obtained the Northeast Consortium (NEALS) Biofluid Repository. Seventeen of 108...
Coformulated sodium phenylbutyrate/taurursodiol (PB/TURSO) was shown to prolong survival and slow functional decline in amyotrophic lateral sclerosis (ALS).
Abstract GGGGCC repeat expansion in C9ORF72 , which can be translated both sense and antisense directions into five dipeptide (DPR) proteins, including poly(GP), poly(GR), poly(GA), is the most common genetic cause of amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD). Here we developed sensitive assays that detect poly(GA) poly(GR) cerebrospinal fluid (CSF) patients with mutations. CSF levels did not correlate age at disease onset, duration, or rate decline ALS Functional...
In the previously reported Comparative Enzyme Replacement Trial With neoGAA Versus rhGAA (COMET) trial, avalglucosidase alfa treatment for 49 weeks showed clinically meaningful improvements in upright forced vital capacity (FVC) percent predicted and 6-minute walk test (6MWT) compared with alglucosidase alfa.
A subset of regulatory B cells in humans and mice has been defined functionally by their ability to produce interleukin (IL)-10. We characterized IL-10-producing (B10) myasthenia gravis (MG) patients correlated them with disease activity responsiveness rituximab therapy.Frequencies B10 from MG healthy controls were monitored fluorescence-activated cell sorting (FACS).MG had fewer than controls, which was associated more severe status. Moreover, who responded well therapy exhibited rapid...
Abstract Myasthenia gravis (MG) is a chronic humoral immunity–mediated autoimmune disorder of the neuromuscular junction characterized by muscle weakness. Follicular helper T (Tfh) cells may be key Th cell subset that promotes MG development, as their major function helping B activation and Ab production. Aberrance thymus-derived Tfh might implicated in diseases including MG; just how circulating cells, especially those from patients with normal thymus, contribute to pathogenesis remains...
Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase (GAA) and subsequent glycogen accumulation. Avalglucosidase alfa, recombinant human GAA enzyme replacement therapy designed for increased cellular uptake clearance, has been studied long-term efficacy safety in patients with late-onset (LOPD). Here, we report up to 6.5 years' experience avalglucosidase alfa during the NEO1 NEO-EXT studies.NEO1 participants LOPD, either treatment...
A summit held March 2023 in Scottsdale, Arizona (USA) focused on the intronic hexanucleotide expansion C9ORF72 gene and its relevance frontotemporal dementia (FTD) amyotrophic lateral sclerosis (ALS; C9ORF72-FTD/ALS). The goal of this was to connect basic scientists, clinical researchers, drug developers, individuals affected by C9ORF72-FTD/ALS evaluate how collaborative efforts across FTD-ALS disease spectrum might break down existing silos. Presentations discussions covered recent...
Objective To 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) slow upright vital capacity (SVC) ≥60% were randomized 1:1:1:1 to 150, 300, or 450 mg twice daily (bid) placebo; active treatment was 4-week follow-up. Primary endpoint change percent predicted SVC at weeks; secondary measures included ALS Functional Rating Scale-Revised (ALSFRS-R) muscle strength...
Abstract Introduction/Aims We tested safety, tolerability, and target engagement of tocilizumab in amyotrophic lateral sclerosis (ALS) patients. Methods Twenty‐two participants, whose peripheral blood mononuclear cell (PBMC) gene expression profile reflected high messenger ribonucleic acid (mRNA) inflammatory markers, were randomized 2:1 to three or placebo treatments (weeks 0, 4, 8; 8 mg/kg intravenous). Participants followed every 4 wk a double‐blind fashion for 16 assessed plasma clinical...
Importance The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play role in disease progression. Objective To determine the effects zilucoplan, an inhibitor C5, individuals with ALS. Design, Setting, Participants Zilucoplan was tested as regimen A HEALEY ALS Platform Trial, phase 2 to 3 multicenter, randomized, double-blind, placebo-controlled perpetual platform clinical trial sharing...
ABSTRACT Introduction/Aims Tofersen is approved for the treatment of amyotrophic lateral sclerosis (ALS) due to superoxide dismutase 1 mutations ( SOD1 ‐ALS). Here we report serious neurologic adverse events (AEs) that occurred in tofersen clinical trials people with ‐ALS. Methods Serious AEs myelitis, radiculitis, aseptic meningitis, and papilledema reported are described. were defined according International Conference Harmonization guidelines, diagnosed by investigators based on symptoms,...
Importance 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. Objective To assess the effect vs placebo on functional outcomes ALS. Design, Setting, and Participants A Study to Evaluate Efficacy Safety Reldesemtiv Patients With Amyotrophic Lateral Sclerosis (COURAGE-ALS) was double-blind, placebo-controlled 3 randomized clinical trial conducted at 83 centers 16...
Abstract Neoplastic lumbosacral plexopathy occurs with some abdominal and pelvic malignancies. Patients present severe pain radiating from the low back down to lower extremities, this progresses weakness. is virtually always associated known malignancy or obvious metastatic disease. Uncommonly, prostate cancer can as a occurring through direct spread. We describe two cases of radiculoplexopathy infiltrative without evidence other extraprostatic The probable etiology tumor spreading along...