Cell-Based Approaches For Modeling and Treating Ataxia-Telangiectasia
Ataxia-Telangiectasia (A-T)This research is being done to better understand the causes of the disease Ataxia-Telangiectasia and, in the longer-term, develop new therapies for the disease using stem cells. Induced pluripotent stem cells (iPSC) are a type of cells that can be made in the laboratory from cells in your body, such as blood cells or skin cells (fibroblasts). These stem cells can then be used for research purposes. For example, stem cells can be used to investigate how the mutation in ATM causes the actual symptoms of Ataxia-Telangiectasia. In addition, the stem cells can be used to screen for drugs that could be helpful to treat the disease or to develop new laboratory techniques to correct the mutation that causes Ataxia-Telangiectasia. where the mutation that causes the disease is corrected by the investigators. The stem cells generated in this study will not be used directly for patient therapy and therefore this research does not have a direct benefit to you. However, it will help advance our understanding of the disease and develop future therapies. Patients who enroll in this study will get all of the standard therapy they would get for their tumor whether or not they participate in this study. There is no extra or different therapy given. The study involves a one-time procedure (either blood collection or skin biopsy).
Coronary Artery Disease in Patients With Friedreich's Ataxia
Friedreich AtaxiaFriedreich's ataxia is a debilitating, inherited disease cause by mutations in a protein called frataxin (FXN). FXN is one of several proteins that controls the production of iron-sulfur clusters, molecules that are essential for energy production in our cells as well as repair of our genetic code embedded in DNA molecules. Friedreich's ataxia (FRDA) and deficiency of FXN results in a nerve disease affecting coordination and a condition called hypertrophic cardiomyopathy (HCM), marked by an abnormal thickening of the heart. Patients with HCM can then develop pulmonary hypertension (PH), a deadly condition of the blood vessels of the lung. While most of the research in FRDA has focused on nerves and heart muscle, alterations in blood vessels of the heart and lung may worsen disease in FRDA. But, the role of FXN in these blood vessels has never been defined. Investigators pilot data suggest that Frataxin (FXN ) deficiency can control senescence and downstream function in various types of Endothelial cells (ECs), investigators hypothesize that Friedreich's Ataxia (FRDA) patients may demonstrate endothelial cells EC abnormalities throughout the vasculature potentially before overt cardiomyopathy develops.
Oxidative Stress, Low Grade Inflammation, Tissue Breakdown and Biomarkers in Cerebrospinal Fluid...
Ataxia TelangiectasiaAtaxia telangiectasia (A-T) is a rare devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. The underlying mechanism and process of neurodegeneration leading to loss of cerebellar neurons and neurological function is largely unknown. Laboratory diagnostic approaches to neurodegeneration in A-T are hampered by sampling issues. It is dangerous, impractical, and not ethically to directly sample brain tissue by surgical biopsy. In contrast cerebrospinal fluid (CSF), a fluid that is in direct contact with brain tissue, is relatively easy to sample in a safe procedure (lumbar puncture). The aim of the proposal is to investigate oxidative stress, low grade inflammation and tissue break down in the brain of A-T patients by analyzing CSF. In addition the alterations in protein expression related to A-T will be quantified by liquid chromatography/mass spectrometry (LC/MS)-based proteomic analysis of CSF from healthy individuals and A-T patients to determine candidate proteins (new biomarkers) which relative expression levels could be used as surrogate marker of disease progression.
4-Aminopyridine in Episodic Ataxia Type 2
Episodic Ataxia Type 2Episodic ataxia type 2 (EA2) is a rare familial neurological condition characterized by debilitating episodes of vertigo and imbalance. Since the serendipitous discovery of dramatic response of EA2 to acetazolamide, acetazolamide has been the first-line treatment for EA2. Yet, for those patients who do not respond to or cannot tolerate acetazolamide, there is no alternative treatment. The purpose of this randomized trial is to test whether 4-aminopyridine may reduce the ataxia episodes in EA2 as an alternative to acetazolamide. Funding Source - FDA OOPD
Study of CAD-1883 for Spinocerebellar Ataxia
Spinocerebellar AtaxiasSpinocerebellar Ataxia Type 18 moreThis is a randomized, double-blind, placebo-controlled Phase 2 study evaluating oral administration of CAD-1883 in the treatment of adults with a genotypic diagnosis of Spinocerebellar Ataxia (SCA). This study offers the opportunity to understand the safety, tolerability, and efficacy of CAD-1883 in the SCA patient population.
Pilot Study of Safety and Efficacy of Sodium Phenylbutyrate in Spinocerebellar Ataxia Type 3
Spinocerebellar Ataxia Type 3DESIGN: Pilot, Phase II, double-blind, placebo-controlled study JUSTIFICATION: In the literature one does not find a pharmacological treatment that changes the natural history of Spinocerebellar ataxtia type 3 (SCA3). Patients with this disease invariably become dependent. OBJECTIVES I. To determine safety and tolerability of phenylbutyrate in patients with SCA3. II. To provide early subsidies on the efficacy of phenylbutyrate in SCA3. DURATION: 12 months of a double-blind study. PLACE OF REALIZATION: Hospital de Clínicas de Porto Alegre, Brazil. NUMBER OF PATIENTS: 20 patients. CONCOMITANT MEDICATIONS: There are no concomitant medications that are prohibited unless they affect safety parameters of this study (hemogram and platelets; fasting serum glucose, AST, ALT, Gamma-GT, Bilirubins, Prothrombin time, Creatinine, Urea, Na, K, chlorides and arterial gasometry; electrocardiogram and echocardiogram). MEDICATIONS UNDER INVESTIGATION: Powdered sodium phenylbutyrate in sachets containing each 3g. At the start of the study, the dose will be 15g/day (five sachets) and may be reduced in case of mild adverse events. OUTCOMES Primary safety outcome: The number of adverse events, interruptions and dose reductions in the two groups (cases and controls). Efficacy outcomes: Efficacy outcomes are the following scores in both groups: NESSCA, SARA, Barthel, BDI, and WHOQol.
Body Composition and Hormonal Status in Ataxia Telangiectasia
Ataxia TelangiectasiaAtaxia telangiectasia (A-T) is a rare devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. In addition to that, a high percentage of patients show dystrophy, growth retardation and poor weight gain. Nevertheless, there are only a few studies assessing this problem. Aim of the present proposal is to investigate the exact body composition, manual muscle strength and hormonal status in patients with A-T compared to healthy controls matched for gender and age. A pelvic sonography in females was performed in order to evaluate the sexual maturity of their inner genitalia. Tanner score was determined to define the physical development. Every subject received a nutritional diary to review its calorie intake and the quality of diet. The investigators expect that the A-T cohort shows an altered body composition, impaired muscle strength, changed hormonal status concerning the sexual hormones and a delayed physical development compared to healthy controls.
NAD+ Precursor Supplementation in Friedreich's Ataxia
Friedreich AtaxiaThe primary objective is to test the safety and tolerability of short-term therapy with a nicotinamide adenine dinucleotide (NAD+) precursor (MIB-626) in adults with Friedreich's Ataxia (FA) without overt heart failure and with a left ventricular ejection fraction ≥ 40%. A key secondary objective is to test the effects of MIB-626 on cardiac and skeletal muscle bioenergetics.
Efficacy of EGb761 in Patients Suffering From Friedreich Ataxia
Friedreich AtaxiaThe purpose of this protocol is to determine the efficacy of EGb 761 120 mg bid versus placebo in patients suffering from Friedreich Ataxia
Could Tai-chi Help Maintain Balance of Spinocerebellar Ataxia Patients
Spinocerebellar AtaxiasTai ChiSpinocerebellar atrophy is the most common autosomal dominant inherited ataxia. There are over thirty subtypes, which characterize neurologic features differently. They all have obvious substantial cerebellar atrophies in image, and unstable gait、ataxia. In general a prevalence of about three cases per 100 000 people is assumed, but this may be an underestimate. Progressive neurologic degeneration, in about 10-20 years, will leads to disability or wheelchair-dependent. Accompanying with fatigue, downhill course of the disease often made patients depressive and hopeless. The recent review of researches concludes no effective therapy for the disease. The purpose of the investigator's study is to explore the Tai-chi exercise effect for spinocerebellar ataxia.