Neuroprotection by Cannabinoids in Huntington's Disease
Status:
Completed
Trial end date:
2012-06-01
Target enrollment:
Participant gender:
Summary
Huntington's disease (HD) is a progressive neurodegenerative disorder, related to an abnormal
expansion of CAG triplets in the huntingtin gene, characterized by motor, cognitive and
behavioral abnormalities, without known effective symptomatic treatment and without known
disease slowing strategy. The most severe neuropathological lesions observed in HD take place
in the striatum, one brain area important in motor control and rich in cannabinoid receptors
(CBR). CBR are subdivided in two classes: CB1R are located in neurons and play a role in
neuronal function; CB2R in brain are located mostly in microglia and modulate
neuroinflammation.
CBR disappear early in the course of HD, before there is a massive drop out of cells in the
striatum. Cannabinoid transmission is also an early event in brains of animal models of HD.
In R6/2 mice, which carry large CAG expansions and develop an early and severe HD phenotype
the suppression of the CB1R gene further accelerate the development of a severe clinical
syndrome and the characteristic brain inclusions and abnormalities of synaptic density. R6/2
treated mice treated with cannabinoids improve their clinical phenotype, their brain lesions,
the synaptic density and the levels of BNDF, a neurotrophic factor which enhances survival
and resistance of striatal neurons.
Preliminary studies of cannabinoids in patients with HD have shown that these compounds are
safe in these patients. Those studies, however, did not show efficacy because 1) they were
underpowered from the statistical point of view, 2) were performed with isolated pure
cannabinoids, instead of the more physiological stimulation with a mixture of compounds, and
3) they did use insensitive clinical parameters instead of sensitive end points, such as
pathogenically important biomarkers.
The investigators propose a phase II trial with combination of cannabinoids with evaluation
of safety, by the profile of adverse events, and efficacy, according to changes of important
biomarkers
Phase:
Phase 2
Details
Lead Sponsor:
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal