Stem cell research in Huntington's disease
18 May 2017
Jasmine Donaldson is a PhD student researching Huntington's disease (HD) at the Centre.
“There are between 6,500 and 8,000 people with Huntington’s disease in the UK. When you look at the number of people with a high genetic risk of inheriting HD in England and Wales the number jumps to 28,480. Each child of a parent with HD has a 50% chance of inheriting the faulty gene and that certainty, that it was caused by one gene, was something that captured my attention when I was first introduced to HD.
“I’d always been interested in neuroscience as I’d been brought up with my mum’s fascination with the human body and brain. She’s an extremely successful aromatherapist and taught me from a young age about the biochemicals in the brain and the risk of illness if they’re not balanced.
“I always remember her saying if she had her time again she’d go into neuroscience. I knew I wanted to do medicine and it spurred me towards neuroscience as an undergraduate at the University of Leeds, where there was a huge focus on neurodegenerative disorders.”
Originally Jasmine was interested in looking at Alzheimer’s disease but began to reconsider after attending a conference in The Hague, hearing from people who were pre-symptomatic with HD and their family members and carers.
“I heard how your life becomes hospital trips and needing to be cared for, which was eye-opening and a push for me to do something about it.”
The nature of HD means it damages nerve cells in the brain, with injury getting progressively worse over time and impacting everything from a person’s movement and cognition (perception, awareness, thinking, judgement) to behaviour.
Getting closer
“Exciting progress is being made in identifying potential ways of slowing down or halting the condition by looking at genes that modify the age at which Huntington's disease develops” said Jasmine.
“HD is caused by a mutation on chromosome 4 in the huntingtin gene. The mutation consists of an expansion of a repeating 'CAG' sequence in the DNA. Unaffected people have between 9 and 35 CAG repeats; a repeat length of 35 or more will invariably cause the disease.
“Generally, the greater the number of repeats, the earlier an individual will develop the disease, however, the age of onset is not determined by repeat length alone.
“My research, funded by the Wellcome Trust, involves using stem cells from patients with HD. Samples of skin cells are collected from a patient and then they are reprogrammed into stem cells which provide us with an unlimited source of any cell type in the body.
“These cells have a disease phenotype which can effectively be looked at in a dish. Using genetic modification, I can introduce changes into the genes we are interested in. If we see a change in the disease phenotype then it highlights particular genes or pathways that might be involved with the disease.”
Researchers are using this method to study the mutation of neurons, and their survival over time, in patients with HD and how they differ from those generated in individuals without the disease.
“Recent genetic studies suggest that variation in DNA repair genes may influence the age at which an individual develops HD.
“The aim of my research is to identify genes that influence how and when the mutation causes symptoms in patients. It’s interesting because people with exactly the same disease mutation show variation in the age at which their symptoms develop.
“The symptoms of HD usually develop when people are between 30 to 50 years old, although they can start much earlier or much later and can differ from person to person, even in the same family. Sometimes, the symptoms are present for a long time before a diagnosis is made. This is especially true when people are not aware that HD is in their family.
“Ultimately my research is leading to the development of drugs that might delay or prevent the onset of HD and provide treatments to those living with the disease."
