In Huntington disease (HD) the identification of biomarkers (besides the number of CAG repeats) may be useful to predict age of onset and disease progression. Biomarkers reflecting different types of pathophysiology in the brain can be used, especially in the early stages of the disease, to predict progression, to monitor effects of novel drug candidates in clinical trials, and in clinical research to better understand the pathogenesis of the disease. A recent focus was on easily accessible biomarkers, coming from peripheral leucocytes and plasma.
In this context, we got informative preliminary results on a circulating small nucleolar RNA (snoRNA), whose plasma level was high in HD patients and normal in HD premanifests and healthy controls.
We now propose a project that will be carried on with both a cross sectional and a longitudinal study design: the cross-sectional study aims to demonstrate snoRNA as specific biomarker for HD, with a significant difference between HD manifest patients and other control groups. We will obtain blood samples from 150 participants, divided into five cohorts (30 pre-HD, 30 HD, 30 healthy donors, 30 psychiatric patients and 30 Alzheimer's disease patients).
The longitudinal phase aim to validate the relationship between snoRNA levels and disease progression. In this phase, we plan to re-sample and clinically re-evaluate at least 15 HD and 15 pre-HD, at a second point of time, that will be on average 72 months apart, considering the characteristics of our population and the time of collection at the baseline.
The snoRNA quantification will be performed by quantitative reverse transcription-PCR (qRTPCR) analysis.
This proposal may improve some aspects of HD management: disclosing new potential therapeutic targets, improving disease course prediction, monitoring current treatments, and providing handy quantitative data to implement possible `preventive therapies¿ for premanifest HD.
We wish to find peripheral "reporters" of the central pathogenic events in HD. This approach may unveil measurable parameters, with multiple applicative potentials:
1) monitor the progression of pathogenic events leading to manifest disease;
2) track disease progression in HD patients;
3) contribute to define a temporal window in which patients could be effectively treated;
4) monitor the efficacy of novel therapies;
5) disclosing new potential therapeutic targets.