Gene Therapy Development and Validation for Huntington's Disease Fibro TG-HD

NCT06444217 | Recruiting

• 1 other identifier: 2024-A00877-40
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Huntington's disease is a rare and fatal monogenic neurodegenerative disorder whose molecular origin is an expansion of CAG triplets within the first exon of the Huntingtin gene. Although a growing number of emerging therapies are in clinical trials, there are no proven neuroprotective or curative treatments approved by the health authorities, as they have not yet demonstrated any real therapeutic benefit or absence of toxicity. Trans-splicing gene therapy is defined as the correction of a mutated endogenous pre-messenger RNA by a therapeutic exogenous pre-messenger RNA. Trans-splicing is a suitable alternative approach, since it is capable of allelic selectivity and replacement of mutated sequences by the wild-type one, criteria that no therapy tested to date meets. This project involves the therapeutic validation of trans-splicing of Huntingtin gene transcripts, and will evaluate its therapeutic effects in vitro, into primary fibroblast cell lines derived from skin biopsies of Huntington's disease patients.

Conditions

Huntington Disease

Keywords

Huntington; gene therapy; trans-splicing; fibroblasts

Outcome Measures

Primary Outcomes (1)

• In vitro validation of a RNA trans-splicing gene therapy for the correction of supernumerary CAG repeats into fibroblasts derived from skin biopsies of patients with Huntington's disease.

  Correction of mutated endogenous transcripts.

  At the inclusion

Secondary Outcomes (1)

• Quantify the expression of Huntingtin protein (HTT) and its (in)usual protein partners.

  At the inclusion

Study Arms (1)

Huntington's patient

EXPERIMENTAL

skin biopsy

Procedure: skin biopsy

Interventions

skin biopsy PROCEDURE

skin biopsy

Huntington's patient

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≤ age ≤ 70 years.
• Signed written, free and informed consent to participate in the study.
• Patients with a CAG≥36 allele (with reduced or full penetrance). penetrance)
• People affiliated to or benefiting from a social security scheme.

You may not qualify if:

• Individuals who have participated in a gene therapy trial using AAV, ASO, mi/si/shRNA administration, likely to disrupt expression, splicing of pre-mRNAs, mRNA splicing, mRNA expression/regulation/translation, energy or protein metabolism directly or indirectly linked to the Huntingtin gene (HTT), its transcripts and proteins.
• Clinical or paraclinical elements that may suggest a differential diagnosis.
• People unable to express their consent.
• Pregnant, breast-feeding or parturient women
• People deprived of liberty by administrative or judicial decision
• People under legal protection (curatorship, guardianship).

Sponsors & Collaborators

• University Hospital, Angers: lead

Study Sites (1)

ABRIAL

Angers, Maine et Loire, 49933, France

RECRUITING

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• VERNY Christophe, MD, PhD

  University Hospital, Angers

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charlotte ABRIAL, PhD

CONTACT

02.41.35.56.15; Charlotte.abrial@chu-angers.fr

Anne-Catherine AUBE-NATHIER, PhD

CONTACT

02 41 34 54 96; acaube-nathier@chu-angers.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2024
• First Posted: June 5, 2024
• Study Start: September 23, 2024
• Primary Completion (Estimated): July 23, 2026
• Study Completion (Estimated): July 23, 2028
• Last Updated: December 13, 2024

Record last verified: 2024-10

Locations

FR (1)