The HD Service Clinic
The Huntington’s clinic runs weekly at the Brain Repair Centre and provides both clinical management of the disease and an opportunity for patients to be involved in ongoing research. Patients are seen by our team of experienced HD specialists including a neurologist, neuropsychologist, representative from the Huntington’s Disease Association and where relevant a psychiatrist.
Enroll-HD is a prospective observational multicentre multi-national cohort study that we are involved in that is being conducted in multiple native languages. Study procedures include annual assessments conducted during study visits that may coincide with regularly scheduled clinic visits.
The study does not include interventional procedures outside of normal clinical care, nor does it include experimental therapies.
Enroll-HD is an open-ended, prospective study. Participants will be asked to participate in as many annual study visits as possible.
Huntington’s Disease (HD) is caused by a mutation in the huntingtin gene. A portion of the gene is expanded and subsequently produces an expanded huntingtin protein. Mutant huntingtin interferes with cell processes and disrupts the overall function of the cell to cause the symptoms of the disease.
The new drug manufactured by IONIS pharmaceuticals, IONIS-HTTRx binds to huntingtin gene to block the production of the huntingtin protein. The drug is in a class of antisense drugs (ASO). The mode of action of IONIS-HTTRx is to bind to huntingtin RNA, telling the cell to destroy it. It is hoped that reducing the levels of the mutant protein in this way will slow or halt disease progression. Preclinical studies with IONIS-HTTRx in animal models have been promising and the purpose of this trial is to test the safety of the drug in humans.
The drug is delivered by injection into the lower back, known as an intrathecal injection (a form of ‘lumbar puncture’). Treatment by this method will mean that the antisense drug is delivered directly to the cells of the brain that are affected by the expression of the huntingtin protein.
The trial is “blinded” which means the patient and the trial doctor will not know whether the patient is given IONIS-HTTRx or placebo. The placebo is an injection that does not contain any active drug. Each patient will receive four doses of IONIS-HTTRx or placebo by an intrathecal injection, with doses four weeks apart. After the last dose, patients will be followed for several weeks to monitor the safety and activity of IONIS-HTTRx.
The study period includes a 13-week period during which you receive the study drug, followed by a 15-week observational period. Patients will need to live near a study centre and have a trial partner – someone who is a family member or close friend and can accompany them to trial visits and be familiar with their HD care.
Problems with thinking in HD
The diagnosis of manifest HD currently relies solely on the motor features but in recent years increasing evidence has shown that the cognitive features begin before the motor features and then evolve differently over time in different ways in different patients. We are looking at theinformation collected during the clinic (above) to both describe the way in which HD changes over time and understanding how, and potentially why, this is different in different people.
In addition we are investigating whether some of the drugs we use to treat the movement problems of HD also change the thinking abilities of the individual. This has involved developed new thinking tests such as: