Delineating the role of HTT Cis-Variants in the pathogenesis of Huntington disease

Provider

Ministry of Education, Youth and Sports

Programme

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Call for proposals

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Main participants

Všeobecná fakultní nemocnice v Praze

Contest type

M2 - International cooperation

Contract ID

31177/2022

Project name in Czech

Delineating the role of HTT Cis-Variants in the pathogenesis of Huntington disease

Annotation in Czech

Huntington disease (HD) is a fatal neurodegenerative disorder without disease modifying therapies. It is well known that HD is always caused by an expanded CAG repeat in the huntingtin (HTT) gene leading to translation of a mutant HTT (mHTT) protein with an expanded polyglutamine stretch in the whole body. However, a number of clinical trials aiming to reduce levels of mHTT has so far failed. There is an inverse correlation between the length of the CAG repeat and the age of onset of typical motor symptoms in HD, that define the age of onset of the clinical HD today. Several large genetic studies including genome-wide and transcription-wide association studies have revealed important genetic modifiers of age-of-onset with cisvariants in HTT suggested to exert major effects. However, these variants have not been considered in the characterization of clinical cohorts of individuals with HD including in the development of or inclusion for clinical trials aiming to modify disease progression. Also, the impact of the genetic variants on the function of mHTT or on neuropathology is not known. Here we propose to fill an important and urgent gap in the knowledge of clinical genetics in HD.

R&D category

AP - Applied research

OECD FORD - main branch

30230 - Other clinical medicine subjects

OECD FORD - secondary branch

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OECD FORD - another secondary branch

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CEP - equivalent branches <br>(according to the <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">converter</a>)

FP - Other medical fields

Realization period - beginning

Jun 1, 2024

Realization period - end

May 31, 2027

Project status

Z - Beginning multi-year project

Latest support payment

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Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data delivery code

CEP24-MSM-9F-R

Data delivery date

Mar 8, 2024

Total approved costs

5,918 thou. CZK

Public financial support

5,918 thou. CZK

Other public sources

0 thou. CZK

Non public and foreign sources

0 thou. CZK