Gene therapy is the treatment of disease by way of the transfer of genetic material into cells.
According to a recent article in Labiotech, an EU publication, gene therapy has become one of the hottest areas of biotech. There have been a number of FDA approvals lately and there are many more therapies in various stages of development.
A Brief History
Genetic diseases were considered incurable. In 1989 protocol was approved that allowed genes to be inserted into cancer patients’ immune cells.
The first gene therapy procedure was performed on Ashanthi DeSilva in 1990. Ashanthi was four-years-old at the time and had been born with severe combined immunodeficiency disease in which antibodies and T cells are genetically missing or disabled. Ashanthi’s immune system had been crippled due to the lack of the adenosine deaminase enzyme (ADA).
The child had to live in an isolated environment as she was continually at risk of infections that could be fatal.
The procedure involved the use of a viral vector which is a modified virus that delivered a functional copy of the missing ADA gene into Ashanthi cells.
The twelve-day therapy was successful. Current reports show her as a healthy eighteen-year-old living in the Chicago suburbs.
And Then a Tragedy
Encouraged by Ashanthi’s successful therapy, researchers launched a number of clinical trials during the next decade.
However, the effort suffered a major setback with the death in 1999 of Jesse Gelsinger, an eighteen-year-old participant in a clinical trial conducted at the University of Pennsylvania.
The disease, called ornithine transcarbamylase deficiency, prevented toxic ammonia from being broken down in his liver.
The cause of the disorder was the mutation of an OTC gene. Therefore, a working copy of the OTC gene was created. It was delivered into Jesse’s cells by way of a modified cold virus (adenovirus) as a vector (transporter).
Jesse had a fatal immune response. He developed a blood-clotting disorder plus kidney, liver and lung failure.
Four days after receiving the treatment Jesse was declared brain dead and taken off life support.
Amid universal shock and media attention, the FDA suspended the university’s gene therapy program. Although the program had been the world’s largest, the university eventually shut it down.
FDA also began investigations into sixty-nine gene therapy programs across the nation. It was decided that Jesse’s death proved the need for more caution and improved vectors.
On The Rebound
The first sign of recovery was the approval by China of a gene therapy called Gendicine for cancer of the neck and head in 2003.
In 2011 Russia approved Neovasculgen to treat peripheral artery disease.
The last few years have seen about four hundred clinical trials. There has been a lot of positive news, funding for product development, and FDA approval at all levels. It appears that the gene therapy revolution is here.
The European Commission approved a drug for lipoprotein lipase deficiency called Glybera in 2012. Glybera’s price tag topped all other drugs worldwide at the time. It was taken off the market in 2017 as it proved to be a commercial failure.
Looking Toward the Future
In the United States, the FDA anticipates approval of between ten to twenty gene and cell therapies annually by the year 2025. One class of viral vectors that will be leading the surge of gene therapies will be adeno-associated viruses (AAVs).
Gene Therapy: The Eyes Have It
Researchers have found that eyes are responsive to the therapy. The EU approved the drug Luxturna in 2018 to treat people who have a rare form of inherited vision loss.
Two companies in Europe, Horama and Nightstar Therapeutics, are focusing on these therapies to treat blindness.
CRISPR is on the Scene
CRISPR’s approach involving the ‘editing out’ of genetic diseases may expand genetic treatment.
A person speaking on behalf of the CRISPR Therapeutics company said that most gene therapies deliver a functional copy of the gene into the cell. He said that they do not stop or reduce the expression of the actual diseased gene.
He went on to explain that gene editing deletes, disrupts or repairs the diseased gene and therefore may be successful in treating genetic disorders.
Gene therapy’s evolution has only just begun. Molecular tools are being developed that will improve the ability to reverse the damage caused by genetic disorders.