New Huntington trial “GENERATION HD1” — UMCG one of two participating Dutch centers
Huntington’s disease is currently incurable but a number of large international therapy trials have been initiated that aim to develop a way to stop disease progression. In Groningen we participate in the so-called GENERATION HD1 trial. This project has been initiated by a large international drug company, Hoffmann LaRoche. Worldwide, 801 affected individuals will be treated over a period of two years with a compound (an ‘antisense oligonucleotide’ or ASO) that lowers the production in the brain of the protein (‘huntingtin’) that is mutated in Huntington’s disease. This mutated protein is the presumed cause of the cellular changes that underlie the gradual worsening of the disease.
Huntington’s disease is a hereditary brain disease that manifests as a gradual worsening of movements: involuntary movements and clumsiness, gait problems and swallowing difficulties. Also, behavioural changes occur, with mood problems and a slowly progressive impairment of planning, attention, concentration and other mental capacities. Ultimately, those affected end up in a nursing home, bedridden, succumbing to complications such as pneumonia or the consequences of prolonged immobility. In the western world about 10 in 100,000 people suffer from the disease, which works out to about 1,700 affected individuals in The Netherlands. About three to five times as many people are mutation carriers – they will develop the condition during their lives.
At the departments of Neurology and Genetics, UMCG, we see many individuals with Huntington’s disease. Together with the specialized out-patient clinic of Noorderbreedte in Grou, Friesland, and nursing homes in Bolsward (Bloemkamp) and Apeldoorn (Atlant) we try to help solving disease related problems encountered by people with the condition and their families.
Huntington’s disease is currently incurable but a number of large international therapy trials have been initiated that aim to develop a way to stop disease progression. In Groningen we participate in the so-called GENERATION HD1 trial. This project has been initiated by a large international drug company, Hoffmann LaRoche. Worldwide, 801 affected individuals will be treated over a period of two years with a compound (an ‘antisense oligonucleotide’ or ASO) that lowers the production in the brain of the protein (‘huntingtin’) that is mutated in Huntington’s disease. This mutated protein is the presumed cause of the cellular changes that underlie the gradual worsening of the disease. Research participants comply with an intensive and demanding protocol, according to which they receive a lumbar puncture every two months. Of these participants, 1/3th receive bimonthly dosages of the actual compound, 1/3th receive placebo and 1/3th alternating actual and placebo compound. The research question is whether those who get the actual compound will have done better after two years than those on placebo. It will be wonderful if those on active drug will not have deteriorated over this period. In The Netherlands, the centers in Groningen and in Leiden participate.
Two other research projects should be mentioned as well. People with manifested Huntington’s disease, as well as mutation carriers without signs or symptoms are being monitored in yearly assessments of movement disorder severity, mental performance and potential behavioural changes. This is also part of a large international research project, called Enroll, that aims to develop a detailed description and analysis of the course of the disease. Of particular interest are the factors that may explain the observed variability between individuals. And, of course, participants are potential candidates for intervention trials. The other project addresses fitness to drive (a car). Which factors predict who, despite being affected, is still able to drive a car and who is no longer?