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.
age ≥ 18 years-old
national health insurance cover
genetically confirmed Huntington's disease diagnosis (≥ 35 CAG repeat in HTT gene exon 1)
written informed consent
protected by law
Huntington's disease stage too Evolved that may interfere with cognitive evaluations or MRI
contraindications to brain MRI
only for patients "with LP": contraindications to LP
Parallel
Brain MRI
Procedure/SurgeryMultimodal brain MRI: volumetry, diffusion tensor, functional rest MRI
Lumbar Punction
Procedure/SurgeryAnalysis of BDNF, Tau, NFL and TrkB in cerebrospinal fluid
Blood sample
GeneticAnalysis of BDNF, Tau, NFL, and Val66Met polymorphism
Cognitive evaluation
Other interventionSymbol Digit Modality Test (SDMT), Stroop test, Trail Making Test, Empan
BDNF(csf) in HD subjects compared to age-matched control subjects (+/- 5 years)
centralized ELISA assay with Simoa - Quanterix kit technology at the Laboratory of Clinical Proteomic Biochemistry of Montpellier, France.
plasmatic BDNF in HD subjects vs controls
Correlation between BDNF in CSF and BDNF in plasma
Correlation between BDNF and disease parameters
Correlation between BDNF in CSF or plasma and: disease severity, assessed through a Scale that quantifies the severity of the disease, the disease burden formula \[(n.CAG-35.5) x age\], the Total Functional Capacity functional scale (TFC), and cognitive scales (Symbol Digit Modalities Test, STROOP test, Trail Making test A and B, direct and indirect digit span); - MRI brain imaging: cerebral and striatal atrophy by morphological imaging, functional resting state MRI, and anatomical connectivity by diffusion tensor imaging
Total Tau and NFL levels in plasma and CSF in HD subjects vs control subjects
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