How gene therapy saves lives | Action Medical Research

Touching Lives - March 2013

How gene therapy saves lives

Last year, Action celebrated 60 years of vital research for babies and children. This year we are delighted to be able to mark another milestone: 40 years of awarding Research Training Fellowships to promising doctors and scientists to support the development of future leaders in children’s research.

One former fellow, whose pioneering work has made a major impact on fighting diseases affecting vulnerable babies and children, is Professor Bobby Gaspar. His medical career is now entering its third decade. One of his career highlights is undoubtedly his involvement in the development of gene therapy, which he has used to ‘correct’ faults in babies’ genes that put them at severe risk of infections.Bobby Gaspar is Professor of Paediatrics and Immunology at the Molecular Immunology Unit at the University College London Institute of Child Health (ICH). “As a young man, if I could’ve imagined my perfect career then the one I have is exactly it!” he says.

Action Medical Research supported Bobby’s early research career – in 1993 he was awarded a fellowship to help him complete his PhD. “This was my academic foundation, it set me on the road to my academic and clinical career,” he explains.

He was studying primary immunodeficiency disorders, which occur when the body’s natural immune system is absent or not working properly. He was therefore keen to put his fellowship to good use to help improve understanding of the underlying genetic causes of those disorders. Previously, immunodeficiency disorders had been treated with bone marrow transplants. But problems occurred when the donor match was poor, and children would die. When Bobby was awarded his fellowship in 1993 he had been working in the Infectious Diseases and Immunology department at Great Ormond Street Hospital, London for a year. “This was originally meant to be only for six months,” he explains. “I was lucky enough to work under the inspiring leadership of Professor Gareth Morgan and the late Professor Roland Levinsky who performed the first bone marrow transplants at Great Ormond Street Hospital in 1979.” Professor Levinsky had also been an Action Medical Research fellow in 1975.

Exciting times

Professors Morgan and Levinsky were looking for a clinical fellow to look after the work for the trials they were undertaking in gene therapy. “I was young and fired up by the work and I was obviously keen to be involved,”
says Bobby. Levinsky, a unique character Bobby remembers, told him in no uncertain terms that after six months he would need to find his own funding to continue the laboratory work.

He says: “This was a very exciting time in the field of gene therapy and at such an early part of my life,” Bobby recalls. “What I really enjoyed was the dynamic interaction of working in a laboratory and seeing at first hand the impact of this work on the ward.” Bobby is grateful to Action Medical Research for the support of his research career and work at just the right moment. “Every researcher needs time to complete a PhD and learn the necessary laboratory skills.
The fellowship awarded to me by Action Medical Research was crucial to my continuing studies and to this advancement in laboratory science, which ultimately informed groundbreaking advances in treatment.”

Pioneering

In 1993 – the same year as Bobby’s fellowship – a girl with severe combined immunodeficiency (SCID) was treated with gene therapy at Great Ormond Street Hospital for the first time in the UK. “It was very exciting to be working with genetic material as a cure for these extremely sick children. It also helped the Institute of Child Health gain international regard and acclaim in this area.” Children with SCID are born without white cells in their blood, which are the cells that fight infection. Those with normal immune systems can fight coughs and colds, but children with SCID don’t have white blood cells and don’t have an immune system, so even the most common coughs and colds can be fatal. Sadly, these children usually die within their first year of life. A boy with SCID survived for 12 years in a plastic, germ-free bubble, which prompted the press and public to refer to the condition as ‘bubble boy disease’.

“What we’ve done is to develop a new way to treat these children,” Bobby says. “We know what the missing gene is – the defective gene – so we make a working copy of that gene in the lab and introduce it into their bone marrow cells, which means that their bone marrow cells have the right signal and information to build a new immune system.”

In 2003, Professor Gaspar and the team at Great Ormond Street Hospital were able to treat a three-year-old boy with SCID. That boy is now 11 years old. “I saw him in clinic only recently” says Bobby. “He is well, in school and leading a completely normal life. It’s incredibly rewarding to see how he’s come on – from such a sick and vulnerable baby with no immune protection to the child I now see living such a full life.”

Around 20 children have now been treated with gene therapy by the team at ICH and around the world, including five with primary immunodeficiency disorders and three with genetic metabolic diseases.

Today, Bobby feels privileged to be working at the forefront of research and treatment of primary immunodeficiencies. “I wanted to be able to develop a treatment that was as effective as bone marrow transplant but safer. The fellowship awarded to me by Action Medical Research was crucial to my continuing studies which informed groundbreaking advances in science – ultimately the prize was in seeing these children get well.”

Help us spread the word