Elevated Bile Acid 3β,5α,6β-Trihydroxycholanoyl Glycine in a Subset of Adult Ataxias Including Niemann-Pick Type C.

Ataxia is a common neurological feature of Niemann-Pick disease type C (NPC). In this disease, unesterified cholesterol accumulates in lysosomes of the central nervous system and hepatic cells. Oxidation by reactive oxygen species produces oxysterols that can be metabolised to specific bile acids.

Embedding Patient Input in Outcome Measures for Long-Term Disease-Modifying Parkinson Disease Trials.

Background: Clinical trials of disease-modifying therapies in PD require valid and responsive primary outcome measures that are relevant to patients.

Objectives: The objective is to select a patient-centered primary outcome measure for disease-modification trials over three or more years.

Methods: Experts in Parkinson's disease (PD), statistics, and health economics and patient and public involvement and engagement (PPIE) representatives reviewed and discussed potential outcome measures.

Stage-Dependent Biomarker Changes in Spinocerebellar Ataxia Type 3.

Spinocerebellar ataxia type 3/Machado-Joseph disease is the most common autosomal dominant ataxia. In view of the development of targeted therapies, knowledge of early biomarker changes is needed. We analyzed cross-sectional data of 292 spinocerebellar ataxia type 3/Machado-Joseph disease mutation carriers.

Outcome Measures for Disease-Modifying Trials in Parkinson's Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative.

Background: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach.

Objective: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials.

Methods: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD.

Stage-dependent biomarker changes in spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies for SCA3, precise knowledge of stage-dependent fluid and MRI biomarker changes is needed. We analyzed cross-sectional data of 292 SCA3 mutation carriers including 57 pre-ataxic individuals, and 108 healthy controls from the European Spinocerebellar ataxia type 3/Machado-Joseph Disease Initiative (ESMI) cohort.

Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson's disease.

An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to phase 3 for those candidates passing an interim signal of efficacy. Replicating this complex innovative trial design in diseases such as Parkinson's disease is appealing, but in addition to the challenges associated with any trial assessing a single potentially disease modifying intervention in Parkinson's disease, a multi-arm platform trial must also specifically consider the heterogeneous nature of the disease, alongside the desire to potentially test multiple treatments with different mechanisms of action. In a multi-arm trial, there is a need to appropriately stratify treatment arms to ensure each are comparable with a shared placebo/standard of care arm; however, in Parkinson's disease there may be a preference to enrich an arm with a subgroup of patients that may be most likely to respond to a specific treatment approach.

A Drug Combination Rescues Frataxin-Dependent Neural and Cardiac Pathophysiology in FA Models.

Friedreich's ataxia (FA) is an inherited multisystemic neuro- and cardio-degenerative disorder. Seventy-four clinical trials are listed for FA (including past and present), but none are considered FDA/EMA-approved therapy. To date, FA therapeutic strategies have focused along two main lines using a single-drug approach: a) increasing frataxin and b) enhancing downstream pathways, including antioxidant levels and mitochondrial function.

Altered pituitary morphology as a sign of benign hereditary chorea caused by TITF1/NKX2.1 mutations.

Benign hereditary chorea (BHC) is a rare genetically heterogeneous movement disorder, in which conventional neuroimaging has been reported as normal in most cases. Cystic pituitary abnormalities and features of empty sella have been described in only 7 patients with BHC to date. We present 4 patients from 2 families with a BHC phenotype, 3 of whom underwent targeted pituitary MR imaging and genetic testing.

From Collar to Coccyx: Truncal Movement Disorders: A Clinical Review.

Background: Movement disorders affecting the trunk remain a diagnostic challenge even for experienced clinicians. However, despite being common and debilitating, truncal movement disorders are rarely discussed and poorly reviewed in the medical literature.

Objectives: To review common movement disorders affecting the trunk and provide an approach for clinicians based on the truncal region involved (shoulder, chest, diaphragm, abdomen, pelvis, and axial disorders).

Vitamin B6 Deficiency in Patients With Parkinson Disease Treated With Levodopa/Carbidopa.

Objective: The aim of the study was to investigate the role of L-DOPA/carbidopa (CD) therapy on vitamin B6 levels in patients with Parkinson disease (PD).

Methods: This is a cross-sectional retrospective study of vitamin B6 plasma levels in 24 patients with PD treated with L-DOPA/CD for 3 or more years, orally or intraduodenally. Vitamin B6 levels in plasma were measured by ELISA.