Clinical Trial

Disease: Huntington's Disease, (NCT05032196)

Disease info:

Huntington’s disease (HD) is a rare, neurodegenerative genetic disease that is characterised by progressive choreatic movements (involuntary, irregular, unpredictable muscle movements), behavioural and psychiatric disturbances and cognitive decline. Although the disease is inherited at birth, symptoms usually don’t manifest until middle age, with the average age at onset being 30-50 years. HD progresses rapidly and is fatal. There is currently no cure for HD and treatments are largely symptomatic and preventative, aiming to improve the quality of life by treating symptoms of chorea and psychiatric decline, and by preventing weight loss, choking and other painful or dangerous symptoms.

HD is caused by a mutation in a CAG trinucleotide repeat in the Huntington gene, located on chromosome 4. Under normal circumstances the CAG repeat contains fewer than 35 repeats and encodes a protein that interacts with neurons in specific brain regions. However, in HD the mutated repeat is expanded, exhibiting substantially longer repeat length and leading to expression of a mutant protein. The longer the repeat expansion, the earlier disease symptoms occur. Degenerative changes to neurons occur through age-dependent exposure to the mutant protein.

HD is inherited in an autosomal-dominant manner, meaning that inheriting only one mutated copy of the Huntington gene will result in disease development. This means that people with Huntington’s disease have a 50% chance of passing it onto their children.

The primary symptoms are cognitive, motor and psychiatric decline due to the death of neurons. Although the precise function of the wild-type huntingtin protein is still poorly defined, it is known to interact with neurons throughout the brain. The mutant huntingtin interacts with these nerve cells and eventually leads to neuronal death. The changes to neurons in brain regions give way to the multiple, complex disease symptoms.

The most common symptom is chorea that progresses rapidly, eventually spreading to all muscles. Dystonia can often be the first sign of motor decline in individuals with HD. This is characterised as uncontrollable muscle movements such as tics and muscle jerks. Cerebellar-related motor decline can occur sporadically. As the disease progresses, dysarthria and dysphagia become serious symptoms, making tasks such as talking and swallowing difficult. Motor ability declines rapidly and patients develop bradykinesia, a rigidity and slowness of movements. All psychomotor processes become extremely difficult for HD patients. Individuals with HD often exhibit cognitive decline such as an inability to retain long-term memory. Psychiatric symptoms such as depression and anxiety are common, especially in the early stages of the disease. Other symptoms include involuntary weight loss and choking.

There is currently no cure for HD. Treatments aim at alleviating disease symptoms such as aberrant muscle movements and psychiatric dysfunction. Symptoms of chorea associated with HD can be treated using neuroleptic medication to block dopamine receptors or depleting agents. In addition to this, as of 2008 the Food and Drug Administration (FDA) has approved tetrabenazine (Xenazine) to treat symptoms of chorea. Psychiatric symptoms can be treated with medication or non-medical care such as psychotherapy, or a combination of the two. A specialised diet can help prevent symptoms of weight loss and choking.

HD is estimated to affect approximately 3-7 per 100,000 individuals of Caucasian ancestry.
Official title:
A Multicenter, Randomized, Double-blind, Placebo Controlled, Phase 1b/2a Study of WVE-003 Administered Intrathecally in Patients With Huntington's Disease (SELECT-HD)


Clinical Operations

Phone: 855-215-4687



New South Wales, Australia
Westmead Hospital, Westmead, New South Wales, Australia, 2145

Victoria, Australia
Monash Health, Clayton, Victoria, Australia, 3168

Royal Melbourne Hospital, Melbourne, Victoria, Australia, 3050

Alberta, Canada
University of Alberta Hospital, Edmonton, Alberta, Canada, T6G 2G3

Ontario, Canada
The Ottawa Hospital, Ottawa, Ontario, Canada, K1H 8L6

Quebec, Canada
Centre Hospitalier de l-Universite de Montreal, Montréal, Quebec, Canada, H2X019

Copenhagen, Denmark
Rigshospitalet, Copenhagen, Denmark, 2100

Hopital Henri Mondor - Hospital, Créteil, France, 94010
Institut du Cerveau et de la Moelle Epiniere, Paris, France, 75646

Bochum, Germany
Katholisches Klinikum Bochum gGmbH, Bochum, Germany, 44791

Muenster, Germany

George-Huntington-Institut GmbH, Muenster, Germany, 48149

Taufkirchen, Germany

kbo-Isar-Amper-Klinikum Taufkirchen (Vils), Taufkirchen, Germany, 84416

Verona, Italy
Centro Ricerche Cliniche Di Verona, Verona, Italy

Leiden, Netherlands
Leiden University Medical Center, Leiden, Netherlands, 2333 ZA

Maastricht, Netherlands
Maastricht University Medical Center, Maastricht, Netherlands, 6229 HX

Gdańsk, Poland
Szpital Sw. Wojciecha, Gdańsk, Poland, 80-462

Warsaw, Poland
Instytut Psychiatrii I Neurologii, Warsaw, Poland, 02-957

Barcelona, Spain
Hospital de la Sanata Creu i Sant Pau, Barcelona, Spain, 08041

Madrid, Spain

Hospital Universitario Ramón y Cajal, Madrid, Spain, 28034

Liverpool, United Kingdom

Royal Liverpool University Hospital, Liverpool, United Kingdom, L7 8XP

Devon, United Kingdom

Royal Devon and Exeter Hospital NHS Trust, Exeter, Devon, United Kingdom, EX2 5DW

Glasgow City, United Kingdom

Royal Hospital for Children, Pharmacy Aseptic Unit, Glasgow, Glasgow City, United Kingdom, G51 4TF

Wales, United Kingdom

Cardiff University, Schools of Medicine and Biosciences, Cardiff, Wales, United Kingdom, CF14 4XW

Study start:
Sep. 6, 2021
54 participants
Gene editing method:
RNA editing oligonucleotide
Type of edit:
Gene silencing
Mutant huntingtin gene
Delivery method:
- In-vivo
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Active recruiting


This is a Phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and PD of WVE-003 in adult patients with early-manifest HD who carry the targeted single nucleotide polymorphism (SNP) - SNP3.

Last updated: May. 29, 2024
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