Neurology Research

Phase 3 CAPTIVATE Trial for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Sponsor: Dianthus
Site Principal Investigator: Dora Leung, MD
Site Co-Investigator: Erin Manning, MD
Contact: Kathleen Peterson
Tel: 917-260-4904
Email: neurologyresearch@hss.edu

HSS Neurology is participating in a new phase 3 clinical trial evaluating DNTH103, an investigational therapy for CIDP. Led by Principal Investigator Dr. Dora Leung, this trial marks a significant step forward in the development of targeted immunotherapies for chronic neuromuscular disease. DNTH103 is an extended half-life human IgG4 monoclonal antibody that selectively inhibits activated C1s, the initiating enzyme of the classical complement pathway. The study is designed in three parts: an open-label induction phase, a randomized double-blind placebo-controlled phase, and a long-term extension phase, collectively spanning over three years of clinical evaluation, including a 40-week safety follow-up. This trial not only investigates the therapeutic efficacy and safety of DNTH103, but also explores its potential to offer durable, precision-targeted immune modulation in CIDP. The study underscores HSS Neurology’s leadership in advancing mechanistic treatments in peripheral neuropathies through rigorously designed international clinical research.

Phase 3 Clinical Trial: Ulixcaltamide (PRAX-944) in Adults with Essential Tremor

Sponsor: Praxis Precision Medicine
Principal Investigator: Alexander Shtilbans, MD

This multicenter study, led by HSS neurologist Dr. Alexander Shtilbans, is to evaluate the therapeutic potential of an investigational drug to treat essential tremors in adults.

PROPEL — A New Phase 3, Multicenter, Randomized, Placebo-controlled, Double-blind Study to Assess the Efficacy and Safety of IMVT-1402 in Patients with Mild to Severe Generalized Myasthenia Gravis (gMG).

Site Principal Investigator: Dr. Dora Leung, MD
Site Co-Investigator: Erin Manning, MD
Contact: Kathleen Peterson
Tel: 917-260-4904
Email: neurologyresearch@hss.edu

HSS Neurology is participating in a Phase 3 global clinical trial evaluating IMVT-1402, a next-generation therapeutic monoclonal antibody for the treatment of gMG. Spearheaded at HSS by Dr. Dora Leung, this randomized, double-blind, placebo-controlled study investigates the efficacy, safety, and pharmacologic profile of IMVT-1402 in patients with mild to severe gMG. IMVT-1402 is a fully human anti-FcRn IgG1 monoclonal antibody, specifically engineered to reduce circulating pathogenic IgG autoantibodies, central drivers of gMG pathophysiology, while minimizing effector functions such as antibody-dependent cellular cytotoxicity. The study targets seropositive patients with anti-AChR, anti-MuSK, or anti-LRP4 antibodies and seeks to validate the role of FcRn inhibition as a precision approach in autoimmune neuromuscular disease. This trial represents a critical step in expanding treatment options for patients with refractory or difficult-to-manage gMG and reflects HSS Neurology’s leadership in advancing immunologically targeted therapies in complex autoimmune disorders. Through this trial, HSS Neurology contributes to expanding targeted, immunomodulatory treatment options in gMG, with the potential to improve functional outcomes and quality of life for patients living with this chronic autoimmune neuromuscular disorder.

MOBILIZE — A study Evaluating Efficacy and Safety of Riliprubart in Participants with Refractory Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).

Site Principal Investigator: Dr. Dora Leung, MD
Site Co-Investigator: Erin Manning, MD
Contact: Kathleen Peterson
Tel: 917-260-4904
Email: neurologyresearch@hss.edu

This global, multicenter, placebo-controlled, Phase 3 study is designed to evaluate the efficacy and safety of riliprubart in adult participants with CIDP who have demonstrated insufficient response or refractoriness to standard-of-care therapies, including intravenous immunoglobulin, subcutaneous immunoglobulin, or corticosteroids. The study will follow a treatment duration of 48 weeks, with the primary objective being to assess riliprubart’s potential to improve clinical outcomes in this patient population. Participants must be at least 18 years of age at the time of signing the informed consent. This pivotal trial is poised to provide valuable insights into a promising therapeutic approach for CIDP, a rare and debilitating peripheral neuropathy, with the potential to significantly enhance treatment options for patients who have not responded adequately to conventional therapies.

VITALIZE — A Study Evaluating Efficacy and Safety of Riliprubart versus Intravenous Immunoglobulin (IVIg) in Participants with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).

Site Principal Investigator: Dr. Dora Leung, MD
Site Co-Investigator: Erin Manning, MD
Contact: Kathleen Peterson:
Tel: 917-260-4904
Email: neurologyresearch@hss.edu

This global, multicenter Phase 3 clinical trial investigates the efficacy and safety of riliprubart, an investigational complement pathway inhibitor, in adults with CIDP who continue to experience residual functional impairment despite maintenance IVIg therapy. The study is designed in two parts: an initial double-blind phase comparing riliprubart with IVIg, followed by an open-label extension in which all participants receive riliprubart monotherapy after IVIg withdrawal. By rigorously comparing these therapeutic strategies, this trial aims to advance the treatment landscape for CIDP and evaluate riliprubart’s potential to provide targeted, sustained disease control.

Data Registry for Neurological Complications Associated with Orthopedic Surgeries

Principal Investigator: Ashley Weng, MD
Co-Investigator: Lan Zhou, MD; PhD; Dora Leung, MD; Erin Manning, MD
Contact: Navdeep Singh Nayyar
Tel: 646-714-6135
Email: neurologyresearch@hss.edu

This Neuromuscular Registry at Hospital for Special Surgery is prospective research aiming at systematically capturing and analyzing neurological complications associated with orthopedic surgeries. The study will register all patients who require post-operative neurology consultation to study the incidence, risks, clinical presentations, diagnosis, management, and prognosis of neurological complications by analyzing perioperative variables, intraoperative neuromonitoring data, neuroimaging and electrodiagnostic test findings, and validated clinical outcomes. The findings may help guide prevention of complications and improvement of surgical outcomes.

Retrospective Study on the Effect of Corticosteroid Administration on Foot Drop following Total Knee Arthroplasty (TKA) and Total Hip Arthroplasty (THA)

Principal Investigator: Dr. Erin Manning, MD
Co-Investigator: Dora Leung, MD
Contact: Navdeep Singh Nayyar
Tel: 646-714-6135
Email: neurologyresearch@hss.edu

This retrospective study conducted at the Hospital for Special Surgery investigates the incidence, etiology, and recovery trajectories of postoperative foot drop following TKA) and THA. Key variables assessed include corticosteroid administration patterns, surgical and anesthetic factors, and detailed postoperative neurological outcomes. Data from diagnostic evaluations incorporating electromyography, nerve conduction studies, and advanced imaging modalities (MRI, CT) that were used to characterize the pattern and severity of neural impairment will be analyzed. This investigation provides critical insights into the pathophysiological underpinnings of postoperative foot drop and informs evolving perioperative strategies aimed at minimizing neurological complications while optimizing functional recovery in lower extremity arthroplasty patients.

Retrospective Study of Diffusion Tensor Imaging and Quantitative Susceptibility Mapping as Potential Biomarkers for Diagnosis and Prognostication in Patients with ALS and PLS

Principal Investigator: Dora Leung, MD
Co-Investigator: Erin Manning, MD
Contact: Navdeep Singh Nayyar
Tel: 646-714-6135
Email: neurologyresearch@hss.edu

This collaborative retrospective study between the Hospital for Special Surgery (HSS) and Weill Cornell Medicine (WCM) aims to evaluate advanced neuroimaging techniques, Diffusion Tensor Imaging (DTI) and Quantitative Susceptibility Mapping (QSM), as potential diagnostic and prognostic biomarkers in patients with Amyotrophic Lateral Sclerosis (ALS) and Primary Lateral Sclerosis (PLS). Given the clinical overlap and diagnostic complexity of these progressive motor neuron disorders, our goal is to determine whether quantitative imaging markers of white matter integrity and iron deposition correlate with disease severity and progression. By analyzing existing imaging and clinical data, this study seeks to enhance diagnostic accuracy, facilitate earlier intervention, and ultimately improve patient care. The findings may support the integration of DTI and QSM into routine MRI protocols, offering clinicians objective tools for differentiating ALS and PLS from mimicking neurological conditions.

Quantitative Mapping of Substantia Nigra Iron in Parkinson's Disease and Controls.

Principal Investigator: Alexander Shtilbans, MD

At the intersection of neurology, radiology, and neurosurgery, the study we are conducting explores the role of aberrant brain iron accumulation in the pathophysiology of Parkinson’s disease. Utilizing advanced magnetic resonance imaging techniques—specifically, quantitative susceptibility mapping (QSM), our research aims to non-invasively measure and characterize iron deposition in key deep brain nuclei across different stages of Parkinson’s disease. Preliminary findings demonstrate that iron accumulation is most pronounced in the substantia nigra and red nucleus, appearing early in the disease course and persisting as the condition progresses. Interestingly, other basal ganglia structures do not show similar alterations, suggesting a region-specific vulnerability. These insights not only advance our understanding of disease mechanisms but also highlight QSM's potential as a sensitive biomarker for disease staging and progression. The work reflects the commitment of scientists at Hospital for Special Surgery and Weill Cornell Medicine to pioneering diagnostic and translational approaches in neurodegenerative research.

Role of Macrophages in Skeletal Muscle Injury and Repair

Principal Investigator: Lan Zhou, MD; PhD
Co-Investigator: Xingyu Wang, PhD

Supported by NIH and institutions, Dr. Lan Zhou’s research team has been conducting this line of research for nearly 20 years. They have found that inflammation in response to acute skeletal muscle injury and chronic injury associated with muscular dystrophy is predominated by macrophage infiltration. Adequate infiltration of macrophages is essential to acute skeletal muscle injury repair, as macrophages phagocytose necrotic tissue and produce myotrophic growth factors to promote muscle regeneration. However, infiltrating macrophages contribute to muscle dystrophic changes in Duchenne muscular dystrophy. But blocking macrophage infiltration via CCR2 ablation is not sufficient to improve muscle dystrophy, because muscle resident macrophages expand and undergo pathogenic activation to contribute to muscle fibrosis. Currently, Dr. Zhou’s team is exploring whether inhibition of both inflammatory macrophage infiltration and resident macrophage expansion could represent a viable therapeutic approach to improve muscle pathology and function in Duchenne muscular dystrophy. The goal of this research is to explore a novel and useful macrophage-based therapy.

Role of Fibro/Adipogenic Progenitors in Skeletal Muscle Injury and Repair

Principal Investigators: Lan Zhou, MD; PhD and Xingyu Wang, PhD

This study is to dissect diverse roles of fibro/adipogenic progenitors (FAPs) in acute and chronic skeletal muscle injury and repair. Being the muscle mesenchymal stromal cells, FAPs play a critical role in promoting muscle injury repair or fibrosis via production of extracellular matrix proteins. Studies by Dr. Lan Zhou’s team and others, using single-cell RNA sequencing, demonstrate that FAPs have diverse functional subsets. They interact with other cells in injured muscles, influencing inflammation, regeneration, and injury repair. Dr. Zhou’s team is currently dissecting the interactions between FAPs and macrophages to further determine inflammation regulation by FAPs during skeletal muscle injury and repair.

Molecular Mechanisms of Paraspinal Muscle Fatty Degeneration Associated with Spine Scoliosis

Principal Investigators: Sohrab Virk, MD; Lan Zhou, MD; PhD and Xingyu Wang, PhD

Collaborating with spine surgery team, this study will explore molecular pathogenic mechanisms underlying paraspinal muscle atrophy and fatty infiltration associated with degenerative spine scoliosis. The goal of this research is to develop targeted interventions to reduce paraspinal muscle degeneration, promote muscle regeneration and function, and improve outcomes before and after spine surgery.

Characterization of Muscle Fatty Degeneration Associated with Massive Rotator Cuff Tear

Principal Investigators: Claire Eliasberg, MD and Xingyu Wang, PhD
Co-Investigators: Lan Zhou, MD; PhD and Scott Rodeo, MD

Rotator cuff tears are the most common cause of pain and disability related to the shoulder. About 25% of rotator cuff repairs fail to heal, and the presence of rotator cuff muscle atrophy and fatty degeneration is a known independent risk factor. Over one-third of patients with full-thickness rotator cuff tears have fatty degeneration of supraspinatus or infraspinatus muscles. Collaborating with physician-scientists in orthopedic surgery, this study will characterize the timing and nature of muscle pathological changes arising after massive rotator cuff tears, as well as the underlying molecular and cellular mechanisms. The goal of this study is to develop novel treatments aimed at preventing or ameliorating muscle degenerative changes to improve patient outcomes.