Liquid fat treatment provides hope for rare childhood disease

Scientists from The University of Queensland (UQ) and Wesley Medical Research have discovered that a liquid fat supplement, triheptanoin, can reverse mitochondrial dysfunction and cell death in patients with the rare degenerative disease known as Ataxia–telangiectasia (A–T). Their work has been published in the journal eBiomedicine.

Estimated to affect one in 100,000–300,000 people in Australia, A–T is a genetic neurodegenerative condition often described as the worst parts of cerebral palsy, muscular dystrophy and cystic fibrosis — with patients facing a 25% lifetime cancer risk. Children appear healthy at birth, but balance and coordination decline at about age two, with most needing a wheelchair by their teenage years.

There is currently no cure or approved treatment for the disease, which leaves teenagers and adults dependent on others for everyday tasks due to a loss of functional skills. But Professor Dave Coman from UQ’s Children’s Health Queensland Clinical Unit said findings from a one-year clinical trial have marked a “huge jump forward” in treatment and improved quality of life.

Mitochondria produce energy within cells to power biological function, but patients with A–T rely on another way to make energy called glycolysis — and if glycolysis is less efficient, patient cells are more susceptible to stress.

“Mitochondria act like a spark plug for powering your cells and in A–T for whatever reason they’re not functioning efficiently,” Coman said.

“With triheptanoin, like a car, we’re hot-wiring it to make it work.

“It’s not a cure, but prior to this we had nothing and all we could offer families was kindness and palliative care.”

Recruitment in the clinical trial was offered to all known A–T Australian patients, with 31 people enrolled from age 4–37 years at multiple institutes across Australia. According to Coman, the study demonstrated “real improvements in quality of life, with participants able to feed themselves and avoid choking on food — which is a big issue, particularly for adults”.

“Their language improved, so their intelligibility, volume of voice, the amount they talk and interact with people increased,” Coman continued.

“Their fatigue levels improved remarkably — kids were able to participate in school, do therapies in the afternoon and participate in family life.”

Emeritus Professor Martin Lavin, from UQ’s Centre for Clinical Research, said the clinical trial showed triheptanoin improved mitochondrial function, targeting a core contributor to disease progression.

“We also found that using triheptanoin and a form of vitamin B3 called nicotinamide riboside reduced cell death in patients’ cells, suggesting a dual treatment for patients,” Lavin said.

The study further identified two key biomarkers — neurofilament light chain and interferon gene signature — which could be useful for monitoring disease progression and treatment for the disorder. According to Coman, “There are things we can learn from this disease that are also translatable to more common disorders.”

The next step in the research is an international clinical trial exploring the effectiveness of triheptanoin and nicotinamide riboside as a joint treatment in collaboration with UQ’s partners in the Netherlands and Norway.

Image credit: iStock.com/frankiefotografie