Leslie Thompson Tackles Huntington’s Disease One Gene at a Time – UCI Beall Applied Innovation – UCI Beall Applied Innovation

The UCI professor has dedicated her career to finding answers to a rare genetic disease’s most crucial questions.

An estimated 30,000 genes make up the human genome, with an individual’s entire uniqueness created by genetic mutations. From tissues and blood as well as distinctive physical features, like eye and hair color to temperament and so much more, genes are the coded instructions for building an entire person. But sometimes those instructions contain errors and genes can mutate to form many different things, including diseases.

One such disease, Huntington’s disease, is a rare, inherited disease triggered by a single genetic mutation that causes a progressive breakdown of nerve cells in the brain and affects over 30,000 people in the U.S. with another 200,000 who are at risk of developing the disease, according to the National Organization for Rare Disorders.

In UC Irvine’s (UCI) School of Medicine and School of Biological Sciences, Leslie Thompson, Ph.D., UCI Chancellor’s professor of Psychiatry and Human Behavior and Chancellor’s professor of Neurobiology and Behavior, has been studying this rare genetic disease for over 30 years. Along with her team at The Thompson Laboratory, they aim to learn more about the disease and find treatments.

PURSUING A PASSION
Originally from New York and then Wisconsin, Thompson first found a passion for music when she discovered the flute. However, after her family moved to Mexico, at age 13, Thompson learned about science through her enthusiastic ninth grade teacher, and her newfound passion for science turned into a decades-long pursuit.

Charlie Smith-Geater, Ph.D., assistant project scientist shows Leslie Thompson, Ph.D., data from an experiment using iPSC neurons on the computer. Keona Wang, staff research associate, takes a break from working at the lab bench.

During her senior year of high school, Thompson’s family moved to California where she attended UC San Diego to study biology. It wasn’t until she was pursuing her Ph.D. at UCI that Thompson discovered her interest in genetics and Huntington’s disease in particular, an interest that was once again propelled by a passionate teacher, the late UCI professor and world-renowned genetic researcher John Wasmuth. During this time, Thompson also met pioneering geneticist Nancy Wexler as well as families affected by the disease, which kept her forever engaged in the research.

Following Wasmuth’s human genetics class, Thompson dove head first into studying Huntington’s disease and, eventually, was on an international consortium that discovered the gene for Huntington’s disease, or the HD gene in 1993. The following year, she also co-identified the genetic mutation for the most common genetic form of short-limbed dwarfism, achondroplasia. However, Huntington’s disease has always been her focus.

“I’ve been working on Huntington’s disease now for over 30 years and I’ve been committed ever since. It’s absolutely a passion,” said Thompson.

Having been a lab tech, researcher and, since 2000, a faculty member, Thompson found a home at UCI and thrives utilizing the resources from one of the top research universities. She is grateful for the support she has received over the years.

“It’s an incredible environment and has incredibly strong neuroscience,” said Thompson. “At the very highest level of leadership, UCI accepts, strengthens and promotes ideas. UCI enables innovation and, at the same time, has that collaborative nature, that nimbleness of being able to put things in place quickly.”

PURELY GENETIC
Unlike other genetic diseases, which can show through mutations in several different genes within a person’s genome, Huntington’s disease is only a single genetic mutation that has a 50 percent chance of inheritance.

And that single mutation can cause a wide range of neurodegenerative symptoms – including psychiatric, physical movement and cognitive – which typically begins somewhere between 35 years of age to 50 years of age, with a life expectancy of 10-15 years after diagnosis. However, Huntington’s disease can strike children and young adults as well.

“A lot of the families say it’s the worst of Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis all lumped together,” said Thompson. “With this disease, you can’t do your job, perform daily tasks or take care of your family.”

Despite the disease’s debilitating effects, Thompson finds the most inspiration when working with the families affected by Huntington’s disease well as working with several foundations, such as Hereditary Disease Foundation, Huntington’s Disease Society of America and HD CARE, a UCI support group.

Jack Reidling, Ph.D., project scientist, speaks with Keona Wang and Leslie Thompson, Ph.D., about the stem cell cultures Wang is showing the group on the computer screen’s microscope image.

“The HD families are incredibly brave, knowledgeable, and interested and go through pain and suffering that most of us will never experience,” said Thompson. “The hope and courage they show every day is constantly inspiring and drives us to keep it in mind with everything we do in the lab.”

TRANSLATING THERAPIES
The Thompson Lab is currently studying how the genetic mutation of Huntington’s disease causes specific brain cells to prompt motor and cognitive skill regressions and premature dysfunction and death. Through years of dedicated research, the lab has utilized Huntington’s disease patient’s skin cells, which are formed into stem cells to model and study the disease.

“The patients donate their skin cells to develop those stem cells,” said Thompson. “Even once patients pass away, we still are working with their cells in the lab. So, their families take some comfort from the fact that their family members are still alive in the lab.”

The lab is also developing a stem cell therapy product to transplant into a patient’s brain in which a specific type of cell called a neural stem cell can start to differentiate neurons and make the damaged neurons functional.

“They have a lot of hope for protecting the brain and then also repairing some of the circuitry that is disrupted in Huntington’s disease. There’s a lot of promise for stem cell approaches,” said Thompson.

With the help of UCI Beall Applied Innovation’s Research Translation Group and Industry Sponsored Research team, Thompson recently entered into a sponsored research agreement as well as an option agreement with AgeX Therapeutics, a biotech company that develops therapeutics for aging and regeneration. And with her technology, the teams are forming their own company to develop cellular therapies to treat neurodegenerative disorders and diseases, such as Huntington’s and Alzheimer’s.

“I would love to see treatments or a cure for Huntington’s disease in my lifetime and I think we will because with the way things are moving, that’s a definite reality,” said Thompson. “This is a global effort and we are one little piece of that. It takes a worldwide village.”

Learn more about The Thompson Lab.

All Photos & Illustrations: Julie Kennedy, UCI Beall Applied Innovation

In celebration of Women’s History Month, UCI Beall Applied Innovation is featuring innovative women who continue to pave new roads for their research and startup companies in the “Advice from Brilliant UCI Women” series. In the video below, UCI Professor Leslie Thompson shares some thoughts and advice:

Produced by UCI Beall Applied Innovation
Directed by Julie Kennedy
Filmed by Julie Kennedy & Ryan Mahar
Edited by Celina Bhandari