It can repair fault in immune system cells to help them lead normal lives
By Kiran N. Kumar
For devastated parents of children born with inherited immune diseases, there is a hope to rectify and help them lead normal lives as a fault in cells of the immune system can be repaired now with a new gene editing technique.
The gene editing technique repairs a genetic problem at its source. If a mutation in a certain gene is producing a dysfunctional protein triggering an inherited disease, it delivers a copy of this gene bereft of the deleterious mutation and thereby to produce a functional protein.
Read: One hour after death, life restored in dead pigâ€™s tissues (August 4, 2022)
As the gene therapy is catching up now, the scientists from University College London (UCL) demonstrated a technique that could lead to new treatment for rare disease CTLA-4 insufficiency of the white blood cells â€“ known as regulatory T cells â€“ and those that protect the body from repeat infections and cancer â€“ known as effector T cells.
The study, published in Science Translational Medicine, showed how it helps patients with the condition, where mutations in a gene cause these T cells to function abnormally causing their own immune system to attack tissues and organs, including blood cells.
It obliterates their immune systemâ€™s â€˜memory,â€™ subjecting them to recurring infections by the same viruses and bacteria, sometimes leading to lymphomas, a type of blood cancer.
Although the current gene editing therapy has been developed for tackling the CTLA-4 insufficiency, researchers say it could pave for an approach suitable to tackle a host of other immune conditions in the future.
Co-senior author, Professor Emma Morris says, â€œGenes that play critical roles in controlling immune responses are not switched on all the time and are very tightly regulated.
â€œThe technique we have used allows us to leave the natural mechanisms controlling gene expression intact, at the same time as correcting the mistake in the gene itself.â€
How does it work?
Taking human cells and using â€˜cutâ€™ and â€˜pasteâ€™ gene editing techniques, with the help of the CRISPR/Cas system, the researchers targeted the faulty gene in T cells taken from patients with CTLA-4 insufficiency.
They repaired the errors and restored them to the levels of healthy T cells. In the case of mice, they were also able to improve symptoms of the disease with injections of gene-edited T cells.
It’s a new approach in “inborn errors of immunity,â€ says co-author, Professor Claire Booth at UCL as the method can reduce the risk of getting lymphoproliferative disease.
CTLA-4 is a protein produced by T cells to control the activity of the body’s immune system and most people carry two working copies of the gene responsible for producing CTLA-4, but those who have only one functional copy produce too little of it to regulate the immune system.
So far, the standard treatment for CTLA-4 insufficiency is a bone marrow transplant to replace the stem cells but transplants are risky and require high doses of chemotherapy and longer period of hospitalization. Moreover, older patients with CTLA-4 insufficiency cannot tolerate the transplant procedure.
The new approach can improve many of the symptoms of the disease, besides being less toxic than a bone marrow transplant, insist researchers.
“Collecting the T cells is easier and, correcting the T cells is easier” and the new approach can also reduce the hospitalization period for those patients who require it.