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Enrolling by invitationNCT05152823Updated Sep 30, 2025

Gene Therapy for IGHMBP2-Related Diseases

A Phase 1/2 interventional study of Gene Therapy in SMARD1 and CMT2S, sponsored by Megan Waldrop. Enrolling by invitation at 1 site in United States. Open to participants aged 2 Months to 14 Years. Per ClinicalTrials.gov, last updated 2025-09-30.

Sponsored by Megan Waldrop · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
10
Allocation
Not applicable
Ages
2 Months to 14 Years
Sex
All
01

Study summary

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

02

Conditions studied

  • SMARD1
  • CMT2S

Keywords

  • IGHMBP2
03

In context

Lead sponsor

Megan Waldrop is the lead sponsor of 2 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
2 Months to 14 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
10 participants (estimated)

Study arms

  • Experimental
    Single Intrathecal Delivery

    Biological: Gene Therapy

Interventions

  • BiologicalGene Therapy

    AAV9 carrying the IGHMBP2 gene.

06

What researchers measure

Primary outcomes

  1. Monitoring for the development of unacceptable toxicity.

    Unacceptable toxicity is defined as the occurrence of two or more unexpected Grade III or higher treatment-related toxicities, as defined by CTCAE 5.0.

    Time frame: 3 years

Secondary outcomes

  1. For pre-ambulant participants, ages less than 18 months, change in the Neuromuscular Gross Motor Outcome (GRO) from baseline

    Time frame: Days 90 and 180, Months 12, 18, 24 and 36

  2. For ambulant participants, change in the 100-meter timed test from baseline

    Time frame: Days 90 and 180, Months 12, 18, 24 and 36

  3. For non-ambulant participants, ages 18 months to 6 years, change in the Neuromuscular Gross Motor Outcome (GRO) from baseline

    Time frame: Days 90 and 180, Months 12, 18, 24 and 36

  4. For non-ambulant participants, ages greater than 6 years, change in the revised upper limb module for SMA (RULM) from baseline

    Time frame: Days 90 and 180, Months 12, 18, 24 and 36

07

Study locations

1 site
  • Nationwide Children's Hospital
    Columbus, Ohio 43205, United States
08

References and documents

Publications

  • 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. PubMed 11528396 ↗
  • 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. PubMed 31802621 ↗
  • 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. PubMed 18802676 ↗
  • 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. PubMed 30598237 ↗
  • 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. PubMed 30385095 ↗
  • 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. PubMed 22157136 ↗
  • 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. PubMed 25439726 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 30, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05152823
Lead sponsor
Megan Waldrop
Responsible party
Megan Waldrop (Professor of Neurology, Nationwide Children's Hospital) — Sponsor-investigator
First posted
Dec 10, 2021
Start date
Nov 4, 2021
Primary completion
Jul 2028 (estimated)
Completion
Jul 2030 (estimated)
Last update
Sep 30, 2025

Study contacts

Megan Waldrop, MD
principal investigator · Nationwide Children's Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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