Clinical Trial: Biomarkers in Autosomal Dominant Cerebellar Ataxia

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Identification of Biomarkers in Patients With Autosomal Dominant Cerebellar Ataxia

Brief Summary: Autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders that are clinically and genetically various. BIOSCA study aims to identify markers of the metabolism (energy production inside the cells) in the blood and the brain of ADCA 1,2,3 and 7 patients and control subjects, in the perspective of future therapeutic trials.

Detailed Summary:

Rational. Autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of neurodegenerative disorders caused by unstable CAG repeat expansions encoding polyglutamine tracts. ADCA have a wide range of neurological symptoms including ataxia of gait, stance, and limbs, cerebellar dysarthria, oculomotor disturbances of cerebellar and supranuclear genesis, retinopathy, optic atrophy, spasticity, extra-pyramidal movement disorders, peripheral neuropathy, sphincter disturbances, cognitive impairment, and epilepsy. Corresponding to neuropathological findings in hereditary ataxia, there are three fundamental patterns of degeneration on MRI: spinal atrophy, olivopontocerebellar atrophy, and cortical cerebellar atrophy. We previously showed an hypercatabolism in premanifest and early stage Huntington's disease (HD), along with a systemic metabolic defect: progressive decrease of the plasmatic branched-chain amino acids (BCAA) - correlated with low serum IGF1 (insulin-like growth factor 1) - and muscle energy metabolism abnormalities measured by 31P-NMR spectroscopy. We also observed a weight loss in SCA1, 3 and mostly SCA7 patients. In addition, we underlined in a preliminary study a significant decrease of the BCAA in SCA1,2,3 and 7 patients, suggesting that an energy deficit would also be implied in SCA pathogenesis. Transcriptional interferences are likely a part of SCA physiopathology, as shown in the retinal cells of a SCA7 mouse model, or as we detected over the cerebellum growth of these mice. The hallmark of the gene expression studies in SCA1 and SCA7 mice points out the implication of IGF1 pathway and IGF1 receptor. As in HD, these transcriptional disorders might witness the metabolic defects above-mentioned.

Study objectives. The primary aim of the study is to provide metabolic and imaging biomarkers in SCA1,2,3 and 7 patients and controls in the pers
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: metabolic biomarkers of SCA [ Time Frame: 12 months or 24 months ]

Original Primary Outcome:

Current Secondary Outcome: imaging biomarkers of SCA [ Time Frame: 24 months ]

Original Secondary Outcome:

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: November 9, 2011
Date Started: November 2011
Date Completion:
Last Updated: December 15, 2015
Last Verified: June 2014