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

Huntington Disease Clinical Trial

— FibroTG-HD  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06444217
• Other study ID #: 2024-A00877-40
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2024
• Est. completion date: July 1, 2028

Study information

• Verified date: May 2024
• Source: University Hospital, Angers
• Contact: Charlotte ABRIAL, PhD
• Phone: 02.41.35.56.15
• Email: Charlotte.abrial[@]chu-angers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: July 1, 2028
• Est. primary completion date: July 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 18 = 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.

Exclusion Criteria:

• 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).

Related Conditions & MeSH terms

• Huntington Disease

Intervention

Procedure:
• skin biopsy
skin biopsy

Locations

Country	Name	City	State
France	ABRIAL	Angers	Maine Et Loire

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Angers

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Quantify the expression of Huntingtin protein (HTT) and its (in)usual protein partners.	At the inclusion	At the inclusion