Gene Therapy Patient Information
Gene therapy is an experimental treatment that involves introducing genetic material into a person’s cells to fight or prevent disease. Researchers are studying gene therapy for a number of diseases, such as severe combined immuno-deficiencies, hemophilia, Parkinson's disease, cancer and even HIV, through a number of different approaches. A gene can be delivered to a cell using a carrier. The most common types of carriers used in gene therapy are altered safe viruses. The technology is still in its infancy, but it has been used with some success as outlined below (see also video 6).
Historic Overview of Gene Therapy
On September 14, 1990, the first approved gene therapy procedure was performed on four-year old patient (see video 1). Born with a rare genetic disease called (SCID), she lacked a healthy immune system, and was vulnerable to every passing germ or infection. Children with this illness usually develop overwhelming infections and rarely survive to adulthood; a common childhood illness is life-threatening. She led a cloistered existence; avoiding contact with people outside her family, remaining in the sterile environment of her home, and battling frequent illnesses with massive amounts of antibiotics.
In her gene therapy procedure, doctors removed white blood cells from the child's body, let the cells grow in the lab, inserted the missing gene into the cells, and then infused the genetically modified blood cells back into the patient's bloodstream. Laboratory tests have shown that the therapy strengthened her immune system by 40%; she no longer has recurrent colds, she has been allowed to attend school, and she was immunized against whooping cough. This procedure was not a cure; the white blood cells treated genetically only work for a few months, after which, the process must be repeated. As of early 2007, she was still in good health, and she was attending college.
The reasons for selecting this disease for the first approved human clinical gene therapy trial is that the disease is caused by a defect in a single gene, which increases the likelihood that gene therapy will succeed. In addition, the gene is regulated in a simple, “always-on” fashion, unlike many genes whose regulation is complex, and the amount of ADA present does not need to be precisely regulated. Even small amounts of the enzyme are known to be beneficial, while larger amounts are also tolerated well.
Although this simplified explanation of a gene therapy procedure sounds like a happy ending, it is little more than an optimistic first chapter in a long story; the road to the first approved gene therapy procedure was rocky and fraught with controversy. Gene therapy actually started around 1984 when Gluzman, Carter & Muzyczka developed a gene delivery system derived from adenoviruses and adeno-associated viruses. Soon it became clear that the biology of human gene therapy is very complex, and there are many techniques that still need to be developed and diseases that need to be understood more fully before gene therapy can be used appropriately. A major drawback came in 1999 with the first gene therapy death (see also video 5).
In 2001, the 500th gene therapy clinical trial was submitted to the FDA/NIH for approval. Whereas in 2003, the first commercial gene therapy medicine (Gendicine ) was available on the market in China. Gendicine is registered for the treatment of head and neck cancers. In November 2005, China approved Oncorine (H101) , an oncolytic adenovirus, to be used in combination with chemotherapy as a treatment for patients with late stage refractory nasopharyngeal cancer. See also sections Gene Therapy in China and Medical Tourism.
In 2008, three groups reported positive results using gene therapy to treat Leber's Congenital Amaurosis (LCA), a rare inherited retinal degenerative disorder that causes blindness in children. The patients had a defect in the RPE65 gene, which was replaced with a functional copy using adeno-associated virus. The LCA trials were conducted independently by groups in the United Kingdom, Florida, and Pennsylvania. The first operation was carried out on a 23 year-old British male in early 2007. In all three clinical trials, patients recovered functional vision without apparent side-effects. These studies, which used adeno-associated virus, have spawned a number of new studies investigating gene therapy for human retinal disease.
In November 2012, the European Commission approved the gene therapy Glybera® (alipogene tiparvovec), a treatment for patients with lipoprotein lipase deficiency (LPLD, also called familial hyperchylomicronemia) suffering from recurring acute pancreatitis. Patients with LPLD, a very rare, inherited disease, are unable to metabolize the fat particles carried in their blood, which leads to inflammation of the pancreas (pancreatitis), an extremely serious, painful, and potentially lethal condition. The approval makes Glybera the first gene therapy approved by regulatory authorities in the Western world.
Ethical and Social Issues in Gene Therapy
The biology of human gene therapy is very complex, and there are many techniques that still need to be developed and diseases that need to be understood more fully before gene therapy can be used appropriately. In addition, because gene therapy involves making changes to the body’s genetic setup, it raises many unique ethical concerns. Scientific and ethical discussions about gene therapy began many years ago, but it was not until 1990 that the first approved human gene therapy clinical trial was initiated. This clinical was considered successful because it greatly improved the health and well-being of the few individuals who were treated during the trial. However, the success of the therapy was tentative, because along with the gene therapy the patients also continued receiving their traditional drug therapy. This made it difficult to determine the true effectiveness of the gene therapy on its own, as distinct from the effects of the more traditional therapy.
Measuring the success of treatment is just one challenge of gene therapy. Research is fraught with practical and ethical challenges. As with clinical trials for drugs, the purpose of human gene therapy clinical trials is to determine if the therapy is safe, what dose is effective, how the therapy should be administered, and if the therapy works. Diseases are chosen for research based on the severity of the disorder (the more severe the disorder, the more likely it is that it will be a good candidate for experimentation), the feasibility of treatment, and predicted success of treatment based on animal models. This sounds reasonable. However, imagine you or your child has a serious condition for which no other treatment is available. How objective would your decision be about participating in the research?
How do researchers determine which disorders or traits warrant gene therapy? Unfortunately, the distinction between gene therapy for disease genes and gene therapy to enhance desired traits, such as height or eye color, is not clear-cut. No one would argue that diseases that cause suffering, disability, and, potentially, death are good candidates for gene therapy. However, there is a fine line between what is considered a "disease" (such as the dwarfism disorder achondroplasia) and what is considered a "trait" in an otherwise healthy individual (such as short stature). Even though gene therapy for the correction of potentially socially unacceptable traits, or the enhancement of desirable ones, may improve the quality of life for an individual, some ethicists fear gene therapy for trait enhancement could negatively impact what society considers "normal" and thus promote increased discrimination toward those with the "undesirable" traits. As the function of many genes continue to be discovered, it may become increasingly difficult to define which gene traits are considered to be diseases versus those that should be classified as physical, mental, or psychological traits.
To date, acceptable gene therapy clinical trials involve somatic cell therapies using genes that cause diseases. However, many ethicists worry that, as the feasibility of germ line gene therapy improves and more genes causing different traits are discovered, there could be a "slippery slope" effect in regard to which genes are used in future gene therapy experiments. Specifically, it is feared that the acceptance of germ line gene therapy could lead to the acceptance of gene therapy for genetic enhancement. Public debate about the issues revolving around germ line gene therapy and gene therapy for trait enhancement must continue as science advances to fully appreciate the appropriateness of these newer therapies and to lead to ethical guidelines for advances in gene therapy research. Major participants in the public debate have come from the fields of biology, government, law, medicine, philosophy, politics, and religion, each bringing different views to the discussion.
More information about the ethics of gene therapy can be found at:
Diseases Treated by Gene Therapy
Gene Therapy was initially meant to introduce genes straight into human cells, focusing on diseases caused by single-gene defects, such as cystic fibrosis, hemophilia, muscular dystrophy (see video 2) and sickle cell anemia (see also Wiley database on indications addressed by gene therapy clinical trials). Three types of diseases for gene therapy can be distinguished:
Click here for an overview of new gene therapy trials or search trials by indication.
Among the most notable advancements in gene therapy are the following. See also Major developments in gene therapy, Gene Therapy: Medicine of the 21st Century and Individualized Drugs & Gene Therapy (video 6). A comprehensive 20 minutes video on gene therapy is also available on the website of CliniGene, called: 'Gene Therapy a new tool to cure human diseases'.
Severe Combined Immune Deficiency (ADA-SCID)
Chronic Granulomatus Disorder (CGD)