To start off this post, we would like to talk about Jeff Carroll. He was born in August 1977 in Seattle (USA). While serving in the army, he found out about his mother’s devastating diagnosis. His mother was diagnosed with a neurodegenerative disease, Huntington’s disease. Later on, Jeff found out that he is also a carrier of the deadly mutation and that he will also develop the symptoms of Huntington’s disease.
Jeff’s reaction to his diagnosis was far from conventional: he began his undergraduate Biology degree at the University of British Columbia (Canada). Later on, he obtained his PhD title after joining the lab of one of the leading experts in the field of neurodegenerative diseases, Dr. Michael Hayden. Thereafter, Jeff dedicated his life to research the disease that will inevitably take his life.
Today’s post is about Huntington’s disease and the medical advances in its diagnosis and treatment.
Huntington’s disease (HD) is a devastating incurable disease that affects motor function. The symptoms of HD begin to manifest typically at 40-50 years old, with extremely rare cases in the early teenage onset. HD is a rather rare disorder and it affects 1 in 10 000 people in the United Kingdom.
The underlying cause of HD is a dominant mutation in the gene that codes for a protein called huntingtin. The dominant nature of the mutation means that HD patients have a 50% chance of passing the mutation to their children. This mutation leads to an abnormally folded huntingtin protein that forms toxic aggregates in the brain, which in turn causes the onset of the disease.
Before the classical symptoms of HD arise, patients experience minor behavioural, motor and cognitive changes. (1) This period is called “pre-manifest period” and it can last up to 15 years before a formal clinical diagnosis of HD. The main symptoms of HD are involuntary, abrupt and sporadically timed movements, which are termed chorea. Other common signs of HD include bradykinesia (slowness of movement), tremor and motor dysfunction.
The diagnosis of HD is based on the so-called “triad of symptoms”:
1) motor impairment (chorea most commonly)
2) cognitive impairment
3) neuropsychiatric features. (2) The HD diagnosis can be confirmed by MRI scans and genetic testing.
Additionally, patients carrying the HD mutation but showing no symptoms can be tested for cognitive impairments that could precede the motor manifestation. Currently, there is an ongoing trial, PREDICT-HD, for a predictive model of motor onset of the HD.
A web-based calculator has been created, which predicts the motor onset of HD based on different neurological markers of the disease. (3)
The success of PREDICT-HD in creating a reliable predictive tool, will be helpful for patients and their families to prepare both mentally and physically for the onset of motor symptoms of HD.
Treatment and management
Management of HD patients involves interdisciplinary teams of professionals, who address a wide range of impacts of this debilitating disease on patients and their families. In many cases, the burden of a caregiver may become too heavy and HD patients are then required to be institutionalised.
Particular emphasis is put on patients with a juvenile-onset, as they commonly experience seizures, behavioural and developmental abnormalities, which may add more challenge in their treatment and management.
The chart above represents the currently used management and treatment strategies of HD
Many people that have a family history of HD, prefer not to have children of their own, as the chances of passing the disease are very high. Nowadays, with the help of in vitro fertilisation and preimplantation genetic diagnosis, people with a family history of HD can rest assured that their offspring is disease-free.
For example, Jeff and his wife Meghan conceived their two healthy children using this technique.
Unfortunately, to date, the vast majority of the HD treatment strategies have low or no efficacy.
One of the most promising studies is led by a professor S. Tabrizi from UCL .(4) In this study, they attempt to address the roots of the disease. They have designed a study where they prevent the translation of the mutated huntingtin gene into the faulty protein. Currently, there are phase 2 clinical trials of this drug. If successful, it will be a game-changer and it will save s lot of lives.
Professor Sarah Tabrizi leading the innovative and promising research
1) Bruyn GW: Huntington's chorea: historical, clinical and laboratory synopsis. Handbook of Clinical Neurology. Volume 6. Edited by: Vinken PJ, Bruyn GW. Elsevier Amsterdam, 1968: 298-378.
2) Paulson HL, Albin RL. Huntington’s Disease. InNeurobiology of Huntington's Disease: Applications to Drug Discovery 2011. CRC Press/Taylor & Francis.
3) Li, K., Furr-stimming, E., Paulsen, J. S., Luo, S., & Investigators, T. P. (2017). Dynamic Prediction of Motor Diagnosis in Huntington’s Disease Using a Joint Modeling Approach, 6, 127–137. https://doi.org/10.3233/JHD-170236.
4) Drew L. How the gene behind Huntington's disease could be neutralized. 2018