Pridopidine in early-stage manifest Huntington's disease: a phase 3 trial.

Huntington's disease (HD) is a rare, neurodegenerative disorder for which only symptomatic treatments are available. The PROOF-HD study was a randomized, double-blind, placebo-controlled phase 3 trial evaluating the efficacy and safety of pridopidine, a selective Sigma-1 receptor agonist, in HD. The primary and key secondary endpoints, change in total functional capacity (TFC) and composite Unified Huntington's Disease Rating Scale (cUHDRS) score at week 65, were not met in the overall population.

Pepinemab: a SEMA4D antagonist for treatment of Huntington's and other neurodegenerative diseases.

Introduction: Huntington's Disease (HD) is a progressive fatal neurodegenerative disease with an unmet need for disease-modifying therapies. Neuroinflammation, particularly astrogliosis, plays a crucial role in the pathogenesis of HD and modulation of this damaging activity and its downstream effects presents a promising therapeutic avenue. Pepinemab, a semaphorin 4D (SEMA4D) blocking antibody, has the potential to serve this purpose.

What Huntington's Disease Patients Say About Their Illness: An Online Direct-to-Participant Pilot Study.

Background: Direct-to-participant online reporting facilitates the conduct of clinical research by increasing access and clinically meaningful patient engagement.

Objective: We assessed feasibility of online data collection from adults with diagnosed Huntington's disease (HD) who directly reported their problems and impact in their own words.

Methods: Data were collected online from consenting United States residents who self-identified as 1) having been diagnosed with Huntington's disease, 2) able to ambulate independently, and 3) self-sufficient for most daily needs.

Safety and efficacy of laquinimod for Huntington's disease (LEGATO-HD): a multicentre, randomised, double-blind, placebo-controlled, phase 2 study.

Background: Laquinimod modulates CNS inflammatory pathways thought to be involved in the pathology of Huntington's disease. Studies with laquinimod in transgenic rodent models of Huntington's disease suggested improvements in motor function, reduction of brain volume loss, and prolonged survival. We aimed to evaluate the safety and efficacy of laquinimod in improving motor function and reducing caudate volume loss in patients with Huntington's disease.

Art therapy as a comprehensive complementary treatment for Parkinson's disease.

Introduction: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. Complementary and alternative therapies are increasingly utilized to address its complex multisystem symptomatology. Art therapy involves motoric action and visuospatial processing while promoting broad biopsychosocial wellness.

Pepinemab antibody blockade of SEMA4D in early Huntington's disease: a randomized, placebo-controlled, phase 2 trial.

SIGNAL is a multicenter, randomized, double-blind, placebo-controlled phase 2 study (no. NCT02481674) established to evaluate pepinemab, a semaphorin 4D (SEMA4D)-blocking antibody, for treatment of Huntington's disease (HD). The trial enrolled a total of 265 HD gene expansion carriers with either early manifest (EM, n = 179) or late prodromal (LP, n = 86) HD, randomized (1:1) to receive 18 monthly infusions of pepinemab (n = 91 EM, 41 LP) or placebo (n = 88 EM, 45 LP).

Emerging therapeutics in Huntington's disease.

Introduction: Huntington's disease is a neurodegenerative disease that is characterized by motor dysfunction, behavioral/psychiatric symptoms, and cognitive impairment. Because of the lack of availability of curative or disease modifying treatments, much of clinical practice in HD care to date has focused on symptomatic treatment. Recent work has created optimism surrounding possible emerging disease modifying therapeutics.

Huntington's Disease: New Frontiers in Therapeutics.

Purpose Of Review: This article describes and discusses new potential disease-modifying therapies for Huntington's disease that are currently in human clinical trials as well as promising new therapies in preclinical development.

Recent Findings: Multiple potential disease-modifying therapeutics for HD are in active development, including direct DNA/gene therapies, RNA modulation, and therapies targeted at aberrant downstream pathways. The etiology of Huntington's disease (HD) is well-known as an abnormally expanded trinucleotide repeat within the huntingtin gene.

Art therapy for Parkinson's disease.

Objective: To explore the potential rehabilitative effect of art therapy and its underlying mechanisms in Parkinson's disease (PD).

Methods: Observational study of eighteen patients with PD, followed in a prospective, open-label, exploratory trial. Before and after twenty sessions of art therapy, PD patients were assessed with the UPDRS, Pegboard Test, Timed Up and Go Test (TUG), Beck Depression Inventory (BDI), Modified Fatigue Impact Scale and PROMIS-Self-Efficacy, Montreal Cognitive Assessment, Rey-Osterrieth Complex Figure Test (RCFT), Benton Visual Recognition Test (BVRT), Navon Test, Visual Search, and Stop Signal Task.

Blood-brain barrier permeability in Parkinson's disease patients with and without dyskinesia.

Objective: Recent studies on a rodent model of Parkinson's disease (PD) have raised the possibility of increased blood-brain barrier (BBB) permeability, demonstrated by histology, autoradiography, and positron emission tomography (PET). However, in human PD patients, in vivo evidence of increased BBB permeability is lacking. We examined the hypothesis that levodopa treatment increases BBB permeability in human subjects with PD, particularly in those with levodopa-induced dyskinesia (LID).

Medical, Surgical, and Genetic Treatment of Huntington Disease.

Huntington disease, a neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, is caused by a CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. Current treatments target symptom management because there are no disease-modifying therapies at this time. Investigation of RNA-based and DNA-based treatment strategies are emerging and hold promise of possible future disease-modifying therapy.

Urodynamic Mechanisms Underlying Overactive Bladder Symptoms in Patients With Parkinson Disease.

Purpose: To assess the urodynamic findings in patients with Parkinson disease (PD) with overactive bladder symptoms.

Methods: We performed a retrospective chart review of all PD patients who were seen in an outpatient clinic for lower urinary tract symptoms (LUTS) between 2010 and 2017 in a single-institution. Only patients who complained of overactive bladder (OAB) symptoms and underwent a video-urodynamic study for these symptoms were included.

Tele-monitored tDCS rehabilitation: feasibility, challenges and future perspectives in Parkinson's disease.

Transcranial direct current stimulation (tDCS) is a modality of non-invasive brain stimulation involving the application of low amplitude direct current via surface electrodes on the scalp. tDCS has been studied in healthy populations and in multiple brain disorders and has the potential to be a treatment for several neuropsychiatric conditions by virtue of its capability of influencing cognitive, motor and behavioral processes. tDCS is a generally safe technique when performed within standardized protocols in research or clinical settings.

Gene therapy reduces Parkinson's disease symptoms by reorganizing functional brain connectivity.

Gene therapy is emerging as a promising approach for treating neurological disorders, including Parkinson's disease (PD). A phase 2 clinical trial showed that delivering glutamic acid decarboxylase () into the subthalamic nucleus (STN) of patients with PD had therapeutic effects. To determine the mechanism underlying this response, we analyzed metabolic imaging data from patients who received gene therapy and those randomized to sham surgery, all of whom had been scanned preoperatively and at 6 and 12 months after surgery.

Mirabegron in patients with Parkinson disease and overactive bladder symptoms: A retrospective cohort.

Introduction: This study aimed to assess the outcomes of mirabegron for the treatment of overactive bladder (OAB) symptoms in patients with Parkinson disease (PD).

Methods: A retrospective study was conducted including patients with PD who received mirabegron 50 mg once daily for OAB symptoms between 2012 and 2017. The primary endpoint was clinical success defined as any improvement in overactive bladder symptoms self-assessed by the patients 6 weeks after mirabegron initiation.

Outcomes of intradetrusor onabotulinum toxin A injection in patients with Parkinson's disease.

Objective: To assess the safety and efficacy of intradetrusor onabotulinum toxin A injections for the treatment of overactive bladder (OAB) in patients with Parkinson's disease (PD).

Methods: All PD patients who underwent intradetrusor injections of onabotulinum toxin A (BoNT-A) for storage symptoms between 2010 and 2017 were included in a retrospective study. A 100 U dose of BoNT-A (Botox®, Allergan Irvine, CA) was used for the first injection in all patients.

Increased putamen hypercapnic vasoreactivity in levodopa-induced dyskinesia.

In a rodent model of Parkinson's disease (PD), levodopa-induced involuntary movements have been linked to striatal angiogenesis - a process that is difficult to document in living human subjects. Angiogenesis can be accompanied by localized increases in cerebral blood flow (CBF) responses to hypercapnia. We therefore explored the possibility that, in the absence of levodopa, local hypercapnic CBF responses are abnormally increased in PD patients with levodopa-induced dyskinesias (LID) but not in their nondyskinetic (NLID) counterparts.

National randomized controlled trial of virtual house calls for Parkinson disease.

Objective: To determine whether providing remote neurologic care into the homes of people with Parkinson disease (PD) is feasible, beneficial, and valuable.

Methods: In a 1-year randomized controlled trial, we compared usual care to usual care supplemented by 4 virtual visits via video conferencing from a remote specialist into patients' homes. Primary outcome measures were feasibility, as measured by the proportion who completed at least one virtual visit and the proportion of virtual visits completed on time; and efficacy, as measured by the change in the Parkinson's Disease Questionnaire-39, a quality of life scale.

Long-term follow-up of a randomized AAV2- gene therapy trial for Parkinson's disease.

We report the 12-month clinical and imaging data on the effects of bilateral delivery of the glutamic acid decarboxylase gene into the subthalamic nuclei (STN) of advanced Parkinson's disease (PD) patients. 45 PD patients were enrolled in a 6-month double-blind randomized trial of bilateral AAV2- delivery into the STN compared with sham surgery and were followed for 12 months in open-label fashion. Subjects were assessed with clinical outcome measures and F-fluorodeoxyglucose (FDG) PET imaging.