After almost two decades, gene therapies have recently started to deliver on their immense promise. Gene therapies have been a part of medicine for almost two decades. Only recently have they started to deliver on their immense promise after a string of setbacks raised doubts about the safety of manipulating human DNA, centre, to treat disease.
The idea behind gene therapy is that by inserting new copies of a particular gene into human cells, it should be possible to correct defects, or to enhance beneficial biological processes. This can be done with viruses, which introduce their own genetic material into the cells they infect, and can be engineered to carry a human gene.
This technique was first performed successfully in 1990, when an American team used it to treat Ashanti de Silva, a four-year-old girl with severe combined immune deficiency (SCID). This genetic disease leaves children without a functioning immune system — it is known as “bubble baby” syndrome because sufferers must often be shielded from germs in a sterile pouch. The technology, however, has since encountered several problems. In 1999 Jesse Gelsinger, an 18-year-old with an inherited liver disease who had volunteered for a gene therapy trial, died after suffering a massive immune reaction to the viral vector. Further safety fears were then raised when five children in an Anglo-French trial of a SCID gene therapy developed leukaemia because the viral vector interfered with a gene that can trigger cancer.
Gene therapy has also failed, so far, in the treatment of diseases such as cystic fibrosis: these affect so many of the body’s tissues that it is difficult to infect all the cells that need to be corrected. And there are ethical concerns about using gene therapy to modify cells permanently, especially if these changes can be passed on to subsequent generations. New viral vectors, however, have lowered the risk of immune reactions and inadvertent activation of cancer genes. Many of these also work only for a short period of time, so any damaging effects should be reversible. Several trials have also started to produce extremely encouraging results. The Anglo-French SCID therapy, which now uses a new vector, seems to be capable of curing the disease indefinitely. Another UCL team, led by Robin Ali, has improved the sight of patients with Leber’s congenital amaurosis, a genetic cause of blindness. Cerepro, an Ark Therapeutics drug that uses the same vector as the foetal growth promoter, has had good results against brain cancer.
What links these success stories is that they involve diseases that affect a particular type of tissue, such as white blood cells or retinal cells, which are relatively simple to target for infection with a modified virus. Severe foetal growth restriction falls into the same category: it should only be necessary to influence the uterine arteries to get a result. The dream of using gene therapy to treat more systemic diseases such as cystic fibrosis, muscular dystrophy or spinal muscular atrophy, however, remains more distant. The challenge of conveying the replacement gene to cells throughout the body is one that still has to be overcome.Read full story »