Vasculitis: developing a new gene therapy for a rare inherited type of blood vessel inflammation

Deficiency of adenosine deaminase 2 (DADA2) is a rare genetic type of vasculitis, a condition that causes inflammation and narrowing of the blood vessels. A child with the condition may experience serious complications such as strokes, heart attacks, and severe skin ulceration. Professor Despina Eleftheriou of UCL Great Ormond Street Institute of Child Health is aiming to develop a new gene therapy that could provide a cure for the condition. If successful, this could ultimately lead to a safer and better treatment for children with DADA2 – and lay the foundations for similar gene therapies for other inherited inflammatory illnesses in the future.

How are children’s lives affected now?

Deficiency of adenosine deaminase 2 (DADA2) is a rare inherited type of vasculitis. A child’s immune system mistakenly attacks their blood vessels, causing them to swell and narrow – and leads to continuous inflammation that can damage tissues and organs.

“While the first symptoms may be mild, a child may go on to develop more serious complications including repeated strokes, problems affecting the immune system, gut perforation and severe skin ulceration,” says Professor Eleftheriou.

DADA2 is caused by faults in a gene that helps to make an enzyme called ADA2, which plays an important role in supporting the lining of blood vessels – and in white blood cell development. Currently, there is no cure for the condition – but treatments are available that can help to reduce symptoms.

“Current treatments include drugs that can damp down the immune system – or, for some children, a bone marrow transplant,” says Professor Eleftheriou. “But these are not always effective and can sometimes have serious side effects.”

How could this research help?

“Our goal is to develop gene therapy as a safe and effective new treatment for children with DADA2,” says Professor Eleftheriou.

The approach involves taking blood stem cells (immature cells that can develop into all types of blood cells) from the patient, introducing a working copy of the ADA2 gene – and then transplanting them back into the patient’s body.

“Building on encouraging results from previous experiments, we will first investigate the best way of getting the gene into patient blood stem cells in the laboratory,” says Professor Eleftheriou.

The researchers will then transplant treated blood stem cells into a laboratory model and evaluate the effects on the body.

“We hope our results will guide the development of an international programme of research into gene therapy for children with DADA2.” says Professor Eleftheriou.

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