Clinical trial NCT05225051: N- Homocysteinylated Huntingtin in Huntington's Disease
Official title: N-homocysteinylated Huntingtin in Huntington's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Huntington Disease
Keywords: homocysteinemia
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2022-02-04
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

Brief summary: Descriptive analysis of N- homocysteinylated Huntingtin in 3 groups of human fibroblasts:

1. presymptomatic HD individuals with UHDRS motor ≤ 5 (Mutated Huntingtin),
2. symptomatic HD individuals with motor UHDRS \> 5 (Mutated Huntingtin)
3. human control cell lines, unmutated Huntingtin

Detailed description: Prospective inclusions of 32 subjects with 24 symptomatic HD patients and 8 presymptomatic HD patients.Rationale: This is a pilot study in humans. Over a period of 2 years, the potential recruitment should make it possible to include 32 patients This number will make it possible to calculate the overall variability of the dosage and to have statistics of position and dispersion in the 2 subgroups identified.

Controls: Eight standardized cell lines from human fibroblasts

Eligibility criteria: Inclusion Criteria:

* Patient with the symptomatic or presymptomatic Huntington's disease gene (CAG \>= 36)
* Molecularly confirmed Huntington's disease
* Patient 18 years of age and older
* Person affiliated to or benefiting from a social security assurance

Exclusion Criteria:

* Person deprived of liberty by a judicial or administrative decision, persons subject to psychiatric care pursuant to Articles L. 3212-1 and L. 3213-1
* Pregnant woman, parturient or nursing mother
* Women of childbearing potential who do not have effective contraception
* Intellectual deterioration preventing the understanding of research

Primary outcomes:
measure: Huntingtin homocysteinylated level
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: Blood levels of B9, B12
timeFrame: Through study completion, an average of 2 years
measure: Blood levels of homocysteinemia
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
Study officials:
affiliation: CHRU Nancy
name: Mathilde Renaud
role: PRINCIPAL_INVESTIGATOR
References:
citation: Geoffroy A, Kerek R, Pourie G, Helle D, Gueant JL, Daval JL, Bossenmeyer-Pourie C. Late Maternal Folate Supplementation Rescues from Methyl Donor Deficiency-Associated Brain Defects by Restoring Let-7 and miR-34 Pathways. Mol Neurobiol. 2017 Sep;54(7):5017-5033. doi: 10.1007/s12035-016-0035-8. Epub 2016 Aug 17.
citation: Bossenmeyer-Pourie C, Smith AD, Lehmann S, Deramecourt V, Sablonniere B, Camadro JM, Pourie G, Kerek R, Helle D, Umoret R, Gueant-Rodriguez RM, Rigau V, Gabelle A, Sequeira JM, Quadros EV, Daval JL, Gueant JL. N-homocysteinylation of tau and MAP1 is increased in autopsy specimens of Alzheimer's disease and vascular dementia. J Pathol. 2019 Jul;248(3):291-303. doi: 10.1002/path.5254. Epub 2019 Mar 19.