View clinical trials related to Spinocerebellar Degenerations.
Filter by:The purpose of this study is to evaluate the long-term safety, efficacy, and pharmacokinetics of KPS-0373 in SCD patients
The purpose of this study is to evaluate the long-term safety, efficacy, and pharmacokinetics of KPS-0373 in SCD patients.
The purpose of this study is to investigate the superiority of KPS-0373 to placebo, and evaluate the safety and pharmacokinetics of KPS-0373 in SCD patients.
The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of dominantly inherited progressive ataxia disorders. More than 30 different gene loci have been identified so far. The most common SCAs, which together account for more than half of all affected families, are SCA1, SCA2, SCA3, and SCA6. Each of these disorders is caused by a translated CAG repeat expansion mutation. SCA1, SCA2, and SCA3 usually have an onset between 30 and 40, and SCA6 usually begins at the age of 50 to 60. In addition to progressive ataxia, SCA1, SCA2, and SCA3 frequently present with additional non-ataxic symptoms, including parkinsonism. Carbidopa/levodopa was found to have a good therapeutic effect on parkinsonism. The SCA6 used to be considered a pure cerebellar disorder. However, a recent large study on natural history of SCAs found that patients with SCA6 often had nonataxia symptoms, an observation that challenges the view that SCA6 is a purely cerebellar disorder. Parkinsonism in SCA6 was rarely reported, except in a case serial, or a small size study in Korean patients. Dopamine transporter (DAT) is a very reliable dopaminergic neuronal marker. Reduction in DAT density detected by I123 SPECT DaTscanTM in the dopaminergic neuron terminal striatum was reported in one small size study consisting of eight SCA6 patients in Korea. There was also a PET study using different radioligand for DAT in a small group of SCA6 patients in Germany, which found sub-clinical change in DAT density in some patients with SCA6. There has been no study so far in the US on parkinsonism and other non-ataxia spectrum and striatal dopaminergic damage in SCA6, probably because non-ataxia feature of SCA6 hasn't received much attention, and also because DaTscanTM hasn't been clinically available in US until recently. The only two published studies on SCA6 and DAT were from Korea and Germany, which were of small subject size. There has been no treatment available for SCA6 so far. Our hypothesis is that parkinsonism and other non-ataxia spectrum and striatal dopaminergic neurodegeneration are part of the SCA6 disease spectrum.
Investigators expect there will be improvement in walking speed and steadiness after taking Dalfampridine, thereby improving activities of daily living and enhancing social and occupational functions for patients with spinocerebellar ataxia.
Congenital ataxias (CA) are rare, non progressive diseases, characterized by psychomotor retardation, hypotonia followed by ataxia. The presence of the "molar tooth" on MRI allowed to define Joubert syndrome, a peculiar form of CA. Apart from this group, CA are mostly associated with cerebellar atrophy or hypoplasia without molar tooth on MRI. CA are a clinically as well as genetically heterogeneous group of diseases. Early-onset ataxias are progressive but may be difficult to distinguish from CA in the first years of the disease. To date, few genes responsible for CA have been identified: ABC7 (X-linked CA associated with sideroblastic anemia), SLC9A6 (X-linked CA associated with severe mental retardation, autism and epilepsy), GPR56 (CA associated with polymicrogyria), ATCAY (pure CA in Cayman isolate); the involvement of the ATCAY and ABC7 genes has never been assessed in a large cohort of CA patients. Primary objective: To assess the frequency of mutations of the ATCAY and ABC7 genes in patients affected with non Joubert congenital or early-onset ataxia. Secondary objective: To identify new loci and/or genes responsible for CA To further describe the clinical phenotype of the CA and to assess the frequency of the various clinical types (pure CA/CA associated with spasticity/ syndromic CA, congenital/early-onset CA, sporadic/familial CA). To describe the clinical phenotype of CA related to mutations in one of analysed genes.
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.
The purpose of this study is to evaluate the efficacy and safety of KPS-0373 compared to placebo in patients with Spinocerebellar Degeneration (SCD).
This is a preliminary study to determine the safety and efficacy of intravenous immune globulin in treating Spinocerebellar Ataxia. The investigators aim to assess changes in clinical measures of disease severity before and after treatment.
The hereditary cerebellar ataxias include diverse neurodegenerative disorders. Hereditary ataxias can be divided into autosomal dominant ataxias (ADCAs), autosomal recessive ataxias (ARCAs), X-linked, and mitochondrial ataxias on the basis of mode of inheritance. The key feature in all these disorders is ataxia typically characterised by poor balance, hand incoordination, postural or kinetic tremor, dysarthria and dysphagia. To date no treatment has been shown to slow progression of the disease and symptomatic therapies are limited to few options that are partially effective. Purkinje cells project inhibitory signals to the deep cerebellar nuclei(DCN) which have a critical role in cerebellar function and motor performance. DCN neurons fire spontaneously in the absence of synaptic input from Purkinje neurons and modulation of the DCN response by Purkinje input is believed to be responsible for coordination of movement, while uncontrolled spontaneous firing of DCN neurons may underlay cerebellar ataxia. Recent studies have demonstrated that small-conductance calcium-activated potassium (SK) channels inhibitor are able to increase DCN firing rate. Since SK channels are critical regulators of DCN firing rate, SK openers such as the drug riluzole may reduce neuronal hyperexcitability and thereby be useful in the therapy of cerebellar ataxia. On this base the investigators published a pilot study in patients with chronic cerebellar ataxia (Ristori et al., Neurology 2010) investigating safety and efficacy of riluzole or placebo administration for 8 weeks. The results demonstrated a significative improvement in International Cooperative Ataxia Rating Scale (ICARS) global score after four weeks and after 8 weeks in the riluzole arm. The present protocol is aimed at verifying the safety and efficacy of riluzole administration for a longer period, in a larger sample size of patients, with more stringent diagnostic criteria (hereditary cerebellar ataxia), respect to the above pilot study. Sixty patients will be enrolled in a double-blind, placebo-controlled trial. By central randomisation, patients will take 50 mg of riluzole or placebo twice daily for 12 months. Treatment effects will be assessed by comparing the Scale for the Assessment and Rating of Ataxia (SARA) before treatment and during therapy at months 3 and 12.