Objectives. Here we aim at testing the activity and expression levels of a restricted number of molecules in peripheral blood cells from patients with Huntington Disease (HD). These molecules were chosen because they are affected in cells or mice expressing mutant huntingtin. Other hereditary neurological diseases both associated and non- associated to polyglutamine (Spinocerebellar Ataxias, SCA, and Friedreich Ataxia) will be considered to evaluate whether similar peripheral alterations are present. Background/rationale. HD is part of a group of hereditary late-onset neurodegenerative diseases that share a similar genetic mutation, characterized by an expansion of glutamine tract in specific proteins. Although genetic test can easily assess the presence of the mutation, no other tests are currently available to monitor disease onset and progression. The identification of reliable peripheral indicators of disease would be especially important in clinical therapeutic trials. Recently, members of this network have shown that alterations in A2A receptor profile can be detected both in experimental HD models and also in lymphocytes from HD patients. Description of the project. On these bases, we plan to establish whether the observed adenosine A2A receptor alterations are also present in other polyglutamine disorders, such as SCAs and to verify if the changes correlate with disease progression and clinical severity: In addition, we will study a group of other biological indicators, including endocannabinoid receptors (CB1and non-CB1), brain-derived-neurotrophic factor (BDNF) mRNA and protein levels, mRNA levels of cholesterol enzyme biosynthetic pathway, in blood of HD and SCA patients. Anticipated output. To make available informative peripheral biomarkers that may implement clinical monitoring of disease progression in future clinical trials evaluating the efficacy of potential therapeutic interventions.
Progetto: Telethon - Unità di Ferrara. Identification of peripheral biological markers of disease in patients with Huntington Disease and other polyglutamine disorders.
BOREA, Pier Andrea
2004
Abstract
Objectives. Here we aim at testing the activity and expression levels of a restricted number of molecules in peripheral blood cells from patients with Huntington Disease (HD). These molecules were chosen because they are affected in cells or mice expressing mutant huntingtin. Other hereditary neurological diseases both associated and non- associated to polyglutamine (Spinocerebellar Ataxias, SCA, and Friedreich Ataxia) will be considered to evaluate whether similar peripheral alterations are present. Background/rationale. HD is part of a group of hereditary late-onset neurodegenerative diseases that share a similar genetic mutation, characterized by an expansion of glutamine tract in specific proteins. Although genetic test can easily assess the presence of the mutation, no other tests are currently available to monitor disease onset and progression. The identification of reliable peripheral indicators of disease would be especially important in clinical therapeutic trials. Recently, members of this network have shown that alterations in A2A receptor profile can be detected both in experimental HD models and also in lymphocytes from HD patients. Description of the project. On these bases, we plan to establish whether the observed adenosine A2A receptor alterations are also present in other polyglutamine disorders, such as SCAs and to verify if the changes correlate with disease progression and clinical severity: In addition, we will study a group of other biological indicators, including endocannabinoid receptors (CB1and non-CB1), brain-derived-neurotrophic factor (BDNF) mRNA and protein levels, mRNA levels of cholesterol enzyme biosynthetic pathway, in blood of HD and SCA patients. Anticipated output. To make available informative peripheral biomarkers that may implement clinical monitoring of disease progression in future clinical trials evaluating the efficacy of potential therapeutic interventions.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
