A glimpse into the future of gene therapy

Being born with a genetic disease represents, for many, unavoidable lifelong treatments. Medical research has tried to develop therapies to treat or alleviate the symptoms of these diseases, and we are now beginning to see truly promising results.

Meet Ollie, a three-year-old boy, born with Hunter Syndrome, a rare inherited disorder. Patients with this disorder carry a genetic error in the gene responsible for producing IDS, an enzyme that breaks down large sugar molecules. Without IDS, these sugars build up inside cells and damage vital organs and tissues. Over time, patients develop joint stiffness, breathing and heart problems, and cognitive decline. Until now, treatment options for Hunter Syndrome have been limited. One approved drug, Elaprase, requires lifelong three-hour infusions every week, costing the patient around £375,000 every year. Although this drug is able to slow progression of symptoms, it is unable to stop cognitive decline.

However, in a gene therapy trial led by University of Manchester, researchers removed Ollie’s stem cells, repaired the faulty gene using a modified virus, and returned the cells to his body. These corrected cells, now able to produce the IDS enzyme, prevented the accumulation of these sugars in his body, including his brain. Today, several months after the procedure, Ollie has recovered from the transplant and is showing amazing progress. This is the first time such technique has been used to treat this disease, with similar approaches being explored to treat other conditions. In another promising clinical trial at University of Manchester, this approach was used to treat metachromatic leukodystrophy (MLD), a genetic condition which causes the build-up of fatty chemicals, resulting in damage to the nervous system.

Whilst exciting, gene therapy is still a growing field. Both clinical trials mentioned here involved a small number of patients, and the long-term effects remain unknown.

The field of gene therapies has previously faced serious setbacks, including cases where patients developed complications such as cancer, years after treatment. Until long-term safety is established, we must remain cautiously optimistic.
We had the immense pleasure of talking to Professor Uta Griesenbach, Professor of Molecular Medicine at the NHLI, and Programme Director for MSc Genes, Drugs and Stem Cells, who echoed this caution. While this breakthrough is an exciting step forward, it must first be shown to work in larger patient groups and to have long-term safety before it can truly transform clinical care. This trial treatment was made possible due to kind funding from LifeArc, a British medical research charity. However, for such therapies to become widely accessible, substantial investment from both industry and private partners will be essential.
“Historically, it has been very difficult to get pharmaceutical industries or event small biotechnology companies interested in [gene therapies for] rare and ultrarare diseases. There are many market failures, not because the treatment is inefficient, but because companies decide they cannot make enough money out of this one-off treatment” - Professor Uta Griesenbach.

On a more positive note, this trial represents more than a successful treatment. It marks a milestone for the gene therapy field, opening doors for treating other genetic disorders. As Professor Griesenbach reflected, advanced therapeutics like gene therapy have become a cornerstone of the UK’s scientific strategy, with the field growing rapidly worldwide. As a lecturer, Professor Griesenbach has recognised growing enthusiasm from students and believes gene therapy is entering a pivotal transition period for further development.

Looking ahead, these treatments may start transforming the lives of children once considered incurable and could even be used to tackle conditions such as cancer, Alzheimer’s, diabetes and beyond. For patients like Ollie, lifelong complications and hospital visits may one day become a thing of the past.