New gene therapy could one day prevent a rare inherited childhood disease before symptoms develop.
Scientists at Brunel University of London and University College London Great Ormond Street Institute of Child Health have developed an experimental stem cell treatment for Friedreich’s ataxia.
The condition progressively damages the nervous system and heart, leaving children unable to walk and often leading to early death from heart failure.
The approach uses genetically modified stem cells to produce frataxin, a protein essential for energy production inside cells.
People with Friedreich’s ataxia cannot make enough of it, causing progressive damage to nerves, muscles and the heart. There is currently no cure and treatments can only manage symptoms.
Researchers say human trials could begin within five years if further funding is found.
In laboratory studies and experiments in mice, the treatment slowed progression of the disease, improving movement and coordination and restoring near normal levels of frataxin in the brain, muscle and heart.
Friedreich’s ataxia is the most common inherited form of ataxia, a group of neurological conditions that affect balance and movement. Symptoms usually begin in childhood, often between the ages of five and ten, and worsen over time. Many patients require a wheelchair in their teens.
“The disease is caused by lack of a protein called frataxin,” said Professor Arturo Sala, Professor of Translational Cancer Biology at Brunel’s Centre for Inflammation Research and Translational Medicine (CIRTM). “So essentially we are replacing and replenishing the levels of the frataxin protein.”
He added that, because the engineered stem cells could remain in the body indefinitely, the treatment may provide a continuous supply of the missing protein.
The researchers removed blood-forming stem cells and modified them in the laboratory using a virus to deliver an engineered frataxin protein. This new engineered version of frataxin can be secreted by blood cells and absorbed by other tissues, allowing it to reach vital organs such as the brain, heart and muscles.
Once returned to the body, the modified cells settle in the bone marrow and begin generating new blood cells that release frataxin into the bloodstream. Instead of repeated injections of replacement proteins, this approach effectively turns a patient’s own cells into long-lasting ‘factories’ that continuously produce the missing protein.
In mice, those given the treatment showed improved motor coordination and fewer neurological problems than untreated animals. Levels of frataxin in the brain, muscle and heart tissues were restored to near normal.
The team also tested the approach using stem cells taken from patients with Friedreich’s ataxia, successfully modifying them in the laboratory to produce the therapeutic protein.
The findings suggest the technique could eventually be delivered using a patient’s own cells, reducing the risk of the body rejecting the therapy after transplantation.
“If the strategy works in patients like it works in mice, it could be a game changer,” said Giorgia Santilli, Associate Professor at UCL Great Ormond Street Institute of Child Health. “If treatment is given early enough, then patients would not develop the disease and would live almost normal lives compared to what we have now.”
However, scientists caution that the research is still at an early stage. Further studies in animals are needed before human trials will begin and funding will be required to move the treatment forward. Professor Sala explained, “the cell and gene therapy strategy will require between 3 to 5 years before being tested in Friedreich's ataxia patients.”
If successful in human trials, the approach could reshape how rare genetic diseases are treated. This could harness modified stem cells as long-lasting biological therapies rather than relying on repeated interventions such as protein injections.
“This is a really interesting study showing promising preclinical data for a future therapy for Friedreich's ataxia,” said Ataxia UK's Director of Research, Dr Julie Greenfield. “On behalf of the community of people affected by Friedreich's ataxia we are grateful for this important development towards the future development of much needed treatments.”
The research involved scientists at Brunel University of London and University College London Great Ormond Street Institute of Child Health and was funded by the Medical Research Council and Friedreich’s Ataxia Research Alliance (FARA).