A pioneering new gene therapy has been developed by UK researchers to target a rare, life-limiting inherited immune disorder. 

Patients with CTLA-4 insufficiency, a rare and life-limiting inherited immune disorder, have new hope as a first-of-its-kind gene therapy is advancing in the UK.

The new therapy is a collaboration between LifeArc, a self-funded medical research organisation, University College London (UCL), NHS Blood and Transplant and Great Ormond Street Hospital.

It will take a novel approach by removing a patient’s faulty gene via a tool in the lab before replacing it within the patient’s own immune cells.

CTLA-4 insufficiency disrupts how the immune system is controlled. CTLA-4 normally acts as an “off switch”, helping to prevent overactivation of white blood cell T-cells. But when this fails, patients can experience debilitating symptoms, usually in childhood. These include bowel inflammation, changes in the numbers of different types of blood cells leading to recurrent infections, and, crucially, significantly reduced life expectancy.

Currently, treatment focuses on managing symptoms, such as suppressing the immune system. In some cases, this is via bone marrow transplant, which comes with major risks.

Promising developments

However, the new research in the UK has yielded encouraging results at early pre-clinical stages. The programme is now set to progress through further development and manufacturing before the first-in-human Phase I clinical trial in up to eight patients, aged between one and 65, is scheduled for 2028.

If successful, this could offer a long-lasting treatment option, reducing the need for lifelong treatment or such invasive transplants. It may also inspire similar paths for treating other rare immune disorders.

“This is a highly collaborative effort to bring a new therapeutic approach to patients with CTLA-4 insufficiency… and represents an important step forward for patients who currently have very limited options,” commented Thomas Fox, principal investigator for the research trial at UCL and consultant haematologist.

It’s not the first time UCL and Great Ormond Street Hospital have collaborated on new gene therapies for life-limiting childhood diseases. The two recently came together to research the liver syndrome arthrogryposis, renal dysfunction and cholestasis, known as ARC, using a model in mice that has proved successful so far.