Delving into the Latest Updates on rHIgM22 with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms-

Target

PDGFRs x bFGF

Action

agonists, stimulants

Mechanism

PDGFR agonists(Platelet-derived growth factor receptor agonists), bFGF agonists(Fibroblast growth factor 2 agonists), Myelin proteins stimulants

Therapeutic Areas

Nervous System Diseases

Active Indication

Demyelinating Diseases

Inactive Indication

Multiple Sclerosis, Relapsing-Remitting

Originator Organization

Acorda Therapeutics, Inc.

Active Organization

Mayo Clinic

Inactive Organization

Acorda Therapeutics, Inc.

License Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 181720L

Sequence Code 181715H

Failure of the immune system to discriminate myelin components from foreign antigens plays a critical role in the pathophysiology of multiple sclerosis. In fact, the appearance of anti-myelin autoantibodies, targeting both proteins and glycolipids, is often responsible for functional alterations in myelin-producing cells in this disease. Nevertheless, some of these antibodies were reported to be beneficial for remyelination. Recombinant human IgM22 (rHIgM22) binds to myelin and to the surface of O4-positive oligodendrocytes, and promotes remyelination in mouse models of chronic demyelination. Interestingly, the identity of the antigen recognized by this antibody remains to be elucidated. The preferential binding of rHIgM22 to sulfatide-positive cells or tissues suggests that sulfatide might be part of the antigen pattern recognized by the antibody, however, cell populations lacking sulfatide expression are also responsive to rHIgM22. Thus, we assessed the binding of rHIgM22 in vitro to purified lipids and lipid extracts from various sources to identify the antigen(s) recognized by this antibody. Our results show that rHIgM22 is indeed able to bind both sulfatide and its deacylated form, whereas no significant binding for other myelin sphingolipids has been detected. Remarkably, binding of rHIgM22 to sulfatide in lipid monolayers can be positively or negatively regulated by the presence of other lipids. Moreover, rHIgM22 also binds to phosphatidylinositol, phosphatidylserine and phosphatidic acid, suggesting that not only sulfatide, but also other membrane lipids might play a role in the binding of rHIgM22 to oligodendrocytes and to other cell types not expressing sulfatide.

01 Apr 2022·Multiple Sclerosis Journal - Experimental, Translational and Clinical

A double-blind, placebo-controlled, single-ascending-dose intravenous infusion study of rHIgM22 in subjects with multiple sclerosis immediately following a relapse

Article

Author: Eisen, Andrew ; Alvarez, Enrique ; Warrington, Arthur E. ; Greenberg, Benjamin M. ; Bowen, James D. ; Zhao, Ping ; Rodriguez, Moses ; Caggiano, Anthony O.

Background Recombinant human immunoglobulin M22 (rHIgM22) has promoted remyelination in animal models and was well tolerated in people with clinically stable multiple sclerosis. Objective Safety/tolerability of a single rHIgM22 dose was investigated following an acute relapse and to determine whether this enhanced CNS/CSF concentrations. Methods Adults (N = 27) with acute relapse were assigned to rHIgM22 (0.5 or 2.0 mg/kg) or placebo. Study included screening/steroid administration periods and 10 study visits over 6 months. rHIgM22 CSF concentrations were assessed on days 2 and 29. Pharmacokinetic and safety samples were taken for up to 60 days. Assessments included adverse events and other clinical measures. Brain magnetic resonance imaging was performed with/without gadolinium. Results rHIgM22 CSF levels were consistent with dose-dependent concentration on both days 2 and 29. Infusion was generally well tolerated during an acute relapse. Immunogenicity was mild. Most adverse events did not appear to be dose dependent, were mild/moderate, and were events often associated with multiple sclerosis. Conclusion Although limited by high variability and small sample size, the data suggest enhanced CNS uptake associated with a drop in CSF levels. This study demonstrated safety of an antibody directed to myelin and oligodendrocytes in the course of active demyelinating disease. Further research into rHIgM22 is warranted. ClinicalTrials.gov: NCT02398461 https://clinicaltrials.gov/ct2/show/NCT02398461

03 Aug 2021·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Remyelination therapies for multiple sclerosis: optimizing translation from animal models into clinical trials

Q2 · MEDICINE

Review

Author: Sutiwisesak, Rujapope ; Warrington, Arthur E. ; Burns, Terry C. ; Rodriguez, Moses

Introduction: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system (CNS). Demyelination, the main pathology in MS, contributes to clinical symptoms and long-term neurological deficits if left untreated. Remyelination, the natural repair of damaged myelin by cells of the oligodendrocyte lineage, occurs in MS, but eventually fails in most patients as they age. Encouraging timely remyelination can restore axon conduction and minimize deficits.Areas covered: We discuss and correlate human MS pathology with animal models, propose methods to deplete resident oligodendrocyte progenitor cells (OPCs) to determine whether mature oligodendrocytes support remyelination, and review remyelinating agents, mechanisms of action, and available clinical trial data.Expert opinion: The heterogeneity of human MS may limit successful translation of many candidate remyelinating agents; some patients lack the biological targets necessary to leverage current approaches. Development of therapeutics for remyelination has concentrated almost exclusively on mobilization of innate OPCs. However, mature oligodendrocytes appear an important contributor to remyelination in humans. Limiting the contribution of OPC mediated repair in models of MS would allow the evaluation of remyelination-promoting agents on mature oligodendrocytes. Among remyelinating reagents reviewed, only rHIgM22 targets both OPCs and mature oligodendrocytes.

100 Deals associated with rHIgM22

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Demyelinating Diseases	Phase 1	United States	Mayo Clinic	30 Sep 2013
Multiple Sclerosis, Relapsing-Remitting	Discovery	United States	Acorda Therapeutics, Inc.	01 Apr 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ECTRIMS2013	Phase 1	Spinal Cord Diseases	-	rHIgM22	jopljrmbok(qorubhblps) = hqsyocuopu ygttclaosw (wwvfhsznsx ) View more	-	30 Sep 2013

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Biosimilar

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