Gene Therapy for IGHMBP2-Related Diseases

NCT ID: NCT05152823

Last Updated: 2025-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ENROLLING_BY_INVITATION

Clinical Phase

PHASE1/PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-04

Study Completion Date

2030-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Open-label, single intrathecal injection study of a AAV9 vector carrying the IGHMBP2 gene for IGHMBP2-related diseases.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

SMARD1 CMT2S

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Single Intrathecal Delivery

Group Type EXPERIMENTAL

Gene Therapy

Intervention Type BIOLOGICAL

AAV9 carrying the IGHMBP2 gene.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Gene Therapy

AAV9 carrying the IGHMBP2 gene.

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Confirmation of two pathogenic variants in the IGHMBP2 gene from a CLIA-certified lab
* Pre-ambulant (not yet walking and less than 18 months) or ambulant (as defined by the ability to walk 10 meters without assistance) or non-ambulant (inability to walk more than 10 meters unassisted)
* Ability to cooperate with functional assessments as per PI's discretion

Exclusion Criteria

* Prior participation in a gene or cell therapy program for any kind.
* Immunizations of any kind in the month prior to the study.
* Active infection based on clinical observations
* Serological evidence of HIV infection, or Hepatitis B or C infection
* Diagnosis of (or ongoing treatment for) an autoimmune disease
* Persistent leukopenia or leukocytosis (WBC ≤ 3.5 10\^3/μL or ≥ 20.0 10\^3/μL) or an absolute neutrophil count \< 1.5 10\^3/μL
* Abnormal liver function as indicated by an elevated GGT (\>2X normal if no other laboratory abnormalities), bilirubin and/or abnormal PT/INR
* Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
* AAV9 binding antibody titers \> 1:50 as determined by ELISA immunoassay performed by Athena Diagnostics
* Abnormal laboratory values in the clinically significant range, based upon normal values in the Nationwide Children's Hospital Laboratory
* Diagnosis of any other systemic illness that increases the risk of gene transfer per the PI's opinion; Has a medical condition or extenuating circumstance that, in the opinion of the PI, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's well-being, safety, or clinical interpretability
* Any requirement for immune modulatory therapy and for which it would be unsafe for the subject to undergo an appropriate wash out period
* Contraindication for intrathecal injection
* A positive JCV antibody test of \>0.40
Minimum Eligible Age

2 Months

Maximum Eligible Age

14 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Megan Waldrop

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Megan Waldrop

Professor of Neurology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Megan Waldrop, MD

Role: PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Grohmann K, Schuelke M, Diers A, Hoffmann K, Lucke B, Adams C, Bertini E, Leonhardt-Horti H, Muntoni F, Ouvrier R, Pfeufer A, Rossi R, Van Maldergem L, Wilmshurst JM, Wienker TF, Sendtner M, Rudnik-Schoneborn S, Zerres K, Hubner C. Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1. Nat Genet. 2001 Sep;29(1):75-7. doi: 10.1038/ng703.

Reference Type BACKGROUND
PMID: 11528396 (View on PubMed)

Saladini M, Nizzardo M, Govoni A, Taiana M, Bresolin N, Comi GP, Corti S. Spinal muscular atrophy with respiratory distress type 1: Clinical phenotypes, molecular pathogenesis and therapeutic insights. J Cell Mol Med. 2020 Jan;24(2):1169-1178. doi: 10.1111/jcmm.14874. Epub 2019 Dec 4.

Reference Type BACKGROUND
PMID: 31802621 (View on PubMed)

Guenther UP, Handoko L, Varon R, Stephani U, Tsao CY, Mendell JR, Lutzkendorf S, Hubner C, von Au K, Jablonka S, Dittmar G, Heinemann U, Schuetz A, Schuelke M. Clinical variability in distal spinal muscular atrophy type 1 (DSMA1): determination of steady-state IGHMBP2 protein levels in five patients with infantile and juvenile disease. J Mol Med (Berl). 2009 Jan;87(1):31-41. doi: 10.1007/s00109-008-0402-7. Epub 2008 Sep 18.

Reference Type BACKGROUND
PMID: 18802676 (View on PubMed)

Viguier A, Lauwers-Cances V, Cintas P, Manel V, Peudenier S, Desguerre I, Quijano-Roy S, Vanhulle C, Fradin M, Isapof A, Jokic M, Mathieu-Dramard M, Dieterich K, Petit F, Magdelaine C, Giuliano F, Gras D, Haye D, Nizon M, Magen M, Bieth E, Cances C. Spinal muscular atrophy with respiratory distress type 1: A multicenter retrospective study. Neuromuscul Disord. 2019 Feb;29(2):114-126. doi: 10.1016/j.nmd.2018.10.002. Epub 2018 Oct 31.

Reference Type BACKGROUND
PMID: 30598237 (View on PubMed)

Tomaselli PJ, Horga A, Rossor AM, Jaunmuktane Z, Cortese A, Blake JC, Zarate-Lopez N, Houlden H, Reilly MM. IGHMBP2 mutation associated with organ-specific autonomic dysfunction. Neuromuscul Disord. 2018 Dec;28(12):1012-1015. doi: 10.1016/j.nmd.2018.08.010. Epub 2018 Aug 29.

Reference Type BACKGROUND
PMID: 30385095 (View on PubMed)

Eckart M, Guenther UP, Idkowiak J, Varon R, Grolle B, Boffi P, Van Maldergem L, Hubner C, Schuelke M, von Au K. The natural course of infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1). Pediatrics. 2012 Jan;129(1):e148-56. doi: 10.1542/peds.2011-0544. Epub 2011 Dec 12.

Reference Type BACKGROUND
PMID: 22157136 (View on PubMed)

Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A, Jaunmuktane Z, Saveri P, Rasic VM, Baets J, Bartsakoulia M, Ploski R, Teterycz P, Nikolic M, Quinlivan R, Laura M, Sweeney MG, Taroni F, Lunn MP, Moroni I, Gonzalez M, Hanna MG, Bettencourt C, Chabrol E, Franke A, von Au K, Schilhabel M, Kabzinska D, Hausmanowa-Petrusewicz I, Brandner S, Lim SC, Song H, Choi BO, Horvath R, Chung KW, Zuchner S, Pareyson D, Harms M, Reilly MM, Houlden H. Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. Am J Hum Genet. 2014 Nov 6;95(5):590-601. doi: 10.1016/j.ajhg.2014.10.002. Epub 2014 Oct 30.

Reference Type BACKGROUND
PMID: 25439726 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

STUDY00002143

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

PS-002 for the Treatment of IgA Nephropathy in Adults
NCT07182227 RECRUITING PHASE1/PHASE2
A Study of Anti-IL-6R mAb Injection in Patients With iMCD
NCT05345522 ACTIVE_NOT_RECRUITING PHASE2
Study of CM310 in Healthy Subjects
NCT06161090 COMPLETED PHASE1