Study of BDNF Pathway Biomarkers in the Cerebrospinal Fluid in Patients With Huntington's Disease

Sponsor
University Hospital, Montpellier
Study ID
NCT04012411
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Accepted

Interventions

  • Brain MRI — PROCEDURE
    Multimodal brain MRI: volumetry, diffusion tensor, functional rest MRI
  • Lumbar Punction — PROCEDURE
    Analysis of BDNF, Tau, NFL and TrkB in cerebrospinal fluid
  • Blood sample — GENETIC
    Analysis of BDNF, Tau, NFL, and Val66Met polymorphism
  • Cognitive evaluation — OTHER
    Symbol Digit Modality Test (SDMT), Stroop test, Trail Making Test, Empan

Study Details

Huntington disease (HD, 1.3/10 000) is an autosomal dominant disease due to an abnormal expansion of CAG triplets in HTT gene. Several pathophysiological mechanisms have been evoked, including an alteration of the signaling pathway of the Brain Derived Neurotrophic Factor (BDNF), a neurotrophic factor involved in the survival of neurons (striatal and hippocampal) and synaptic plasticity. BDNF is synthesized at the level of cortical neurons and transported, through the axonal transport in which the Htt is involved, to the nerve endings; it's then secreted in response to excitatory synaptic activity, especially at the level of glutamatergic synapses. Besides, at the postsynaptic level it binds with great specificity to TrkB receptors (tropomyosin-related kinase receptors B) with a neuroprotective effect on dendritic and axonal growth and an increase in synaptic plasticity, especially at the level of the striatum and the hippocampus. BDNF is decreased in the brain of animal models, as well as in patients with HD; the alteration of this pathway would occur in the early stages of the disease. In the context of concomitant multiple treatments, the BNDF pathway may be one of the therapeutic targets of HD. Moreover, in HD it remains essential to detect biological markers representative of the different pathogenic pathways that can be tested in vivo in humans to confirm the hypotheses developed at the level of basic research; these biomarkers could subsequently become biomarkers of disease progression and/or biomarkers of therapeutic efficacy of potential targeted treatments. Therefore, this study aims to characterize potential biomarkers of the BNDF pathway in plasma and CSF in subjects with HD and to confirm the importance of this pathogenic mechanism in vivo in humans.

Key Dates

First listed
Jul 9, 2019
Start date
Mar 3, 2020
Status verified
Feb 2026
Primary completion
Sep 30, 2027
Completion
Sep 30, 2027

Study Design

Enrollment
135 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE

Arms

  • Active Comparator: Patient with LP
    Huntington's disease patients who agreed to have LP
  • Active Comparator: Patient without LP
    Huntington's disease patient with contraindication to LP or refusal to have LP
  • No Intervention: Control Group
    Retrospective study with biologic samples of patients without Huntington's disease

Primary Outcome Measure

BDNF(csf) in HD subjects compared to age-matched control subjects (+/- 5 years) [ Time Frame: Inclusion ]

Central Contacts

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