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Gene Therapy Patient Information

Gene therapy is a 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 growing fast and the first gene therapy products are available on the market.

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.

Video 1: First gene therapy trial for
SCID patient (YouTube, 1:15)
Video 2: Gene therapy for Muscular Dystrophy (YouTube, 1:29)

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 Medical Tourism and Gene Therapy Products on the Market.

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 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia. Neovasculogen is a plasmid encoding the CMV promoter and the 165 amino acid form of VEGF.

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. The commercial rollout of Glybera began in late 2014. See alsoGene Therapy Products on the Market.

In February 2015 LentiGlobin BB305, a gene therapy treatment undergoing clinical trials for treatment of beta thalassemia gained FDA "breakthrough" status after several patients were able to forgo the frequent blood transfusions usually required to treat the disease. In March of 2015, scientists, including an inventor of CRISPR, urged a worldwide moratorium on germline gene therapy, writing “scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans until the full implications are discussed among scientific and governmental organizations. In December, scientists of major world academies called for a moratorium on inheritable human genome edits, including those related to CRISPR-Cas9 technologies, but that basic research including embryo gene editing should continue.

n April 2016 the European Medicines Agency and the European Commission endorsed a gene therapy treatment called Strimvelis. This treats children born with adenosine deaminase deficiency and who have no functioning immune system. This was the second gene therapy treatment to be approved in Europe. In October, Chinese scientists reported they had started a trial to genetically modify T-cells from 10 adult patients with lung cancer and reinject the modified T-cells back into their bodies to attack the cancer cells. The T-cells had the PD-1 protein (which stops or slows the immune response) removed using CRISPR-Cas9.

In 2017 Kite Pharma announced results from a clinical trial of CAR-T cells in around a hundred people with advanced Non-Hodgkin lymphoma. In March, French scientists reported on clinical research of gene therapy to treat sickle-cell disease. In August 2017, the FDA approved Kymriah (tisagenlecleucel) for acute lymphoblastic leukemia. This is the first form of gene therapy to be approved in the United States. In October 2017, a similar therapy called Yescarta (axicabtagene ciloleucel) was approved by the FDA for non-Hodgkin lymphoma.

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:

Moral and Ethical Issues in Gene Therapy by Dr Donald M.Bruce
Ethical aspects of gene therapy by Alex Mauron, Associate professor of bioethics
Ethical Issues in Human Gene Therapy by LeRoy Walters, Kennedy Institute of Ethics, Georgetown University
The Ethics of Gene Therapy by Emilie R. Bergeson

Video 3: The Ethics of Genetically Engineering Children (YouTube, 5:52)
Video 4: Gene Therapy and Ethics (YouTube, 8:58)

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:

  Monogenic disorders, single locus (gene) is defective and responsible for the disease, 100% heritable. Examples: Sickle cell anemia, Severe Combined Immunodeficiency (ADA-SCID / X-SCID), Cystic fibrosis, Hemophilia, Duchenne muscular dystrophy, Huntington’s disease, Parkinson’s, Hypercholesterolemia, Alpha-1 antitrypsin, Chronic granulomatous disease, Fanconi Anemia and Gaucher Disease.
  Polygenic disorders, multiple genes involved, disease may be dependent on environmental factors and lifestyle. Examples: Heart disease, Cancer, Diabetes, Schizophrenia and Alzheimer’s disease.
  Infectious diseases, such as HIV.

Click here for an overview of new gene therapy trials or search trials by indication.

Remarkable strides have been achieved through gene therapy in the field of medical treatment, leading to extraordinary advancements in combating a wide spectrum of genetic disorders and diseases. 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: 'Gene Therapy a new tool to cure human diseases'. Some of the most notable breakthroughs encompass:

Severe Combined Immune Deficiency (ADA-SCID)
Commonly referred to as "bubble boy disease," ADA-SCID is a condition where children are born with compromised immune systems, rendering them highly susceptible to infections. Pioneering research in Italy marked a significant milestone by achieving a form of "cure" or long-term correction for patients with this genetic disorder. This innovative approach involved introducing a therapeutic gene known as ADA into bone marrow cells within a controlled laboratory setting. Subsequently, these genetically modified cells were reintroduced into the patients, effectively restoring their immune systems. This groundbreaking procedure has enabled treated patients to lead normal lives without requiring further interventions. (see also Description of ADA deficiency, ADA: The First Gene Therapy Trial, from the National Institutes of Health and

Chronic Granulomatus Disorder (CGD)
CGD is a genetic disorder impairing the immune system's ability to combat bacterial and fungal infections, often leading to life-threatening consequences. Building upon techniques akin to the ADA-SCID trial, researchers in Germany successfully treated CGD patients. The genetically corrected immune systems of these individuals have provided robust defense against microbial infections for a minimum of two years.

Hemophilia, characterized by impaired blood clotting, poses the risk of severe internal and external bleeding. A clinical trial conducted in the United States aimed to address this issue by introducing therapeutic genes into patients' livers. This approach granted patients the ability to achieve normal blood clotting times. Nonetheless, the therapeutic effects were transient due to the immune system recognizing the genetically modified liver cells as foreign entities. Strategies involving immune suppression or alternative gene delivery methods are currently being explored to attain more sustainable results.

Blindness (Leber's Congenital Amaurosis)
Leber's congenital amaurosis, an uncommon inherited eye disease resulting in profound vision loss or blindness from birth or infancy, has spurred pioneering gene therapy clinical trials. Research conducted at institutions like Moorfields Eye Hospital and University College London has yielded promising outcomes in restoring vision or slowing the disease's progression through gene therapy techniques. The first patient was operated upon in early 2007. Researchers at Children's Hospital of Philadelphia and the University of Pennsylvania have treated six young people via gene therapy. Eye Surgeon Dr. Al Maguire and gene therapy expert Dr. Jean Bennett developed the technique used by the Children's Hospital (see also video 5).

Gene therapy has introduced groundbreaking approaches for cancer treatment, encompassing strategies such as ssuicide gene therapy, oncolytic virotherapy, anti-angiogenesis, and therapeutic gene vaccines. Cancer research constitutes a substantial portion of gene therapy trials, accounting for approximately two-thirds. Advanced-phase trials, including Phase III trials of Ad.p53 for head and neck cancer, Phase III gene vaccine trials for prostate and pancreatic cancer, and Phase I/II trials for various cancers affecting the brain, skin, liver, colon, breast, and kidney, are presently underway and conducted in academic medical centers and biotechnology companies.

Neurodegenerative Diseases
Recent gene therapy advancements offer hope for addressing neurodegenerative disorders such as Parkinson's Disease and Huntington's Disease. Positive results in animal models have spurred the initiation of Phase I clinical trials for these conditions, providing critical insights into gene therapy's potential in treating neurodegenerative disorders.

Gene therapy research has opened avenues for effective treatments in mesothelioma patients. While specific gene therapy approaches are tailored to different cancers, preliminary studies have shown promise in treating mesothelioma. Clinical trials involving suicide genes have exhibited encouraging early results. Nevertheless, further research is needed to refine and develop effective gene therapy treatments for this condition.

Cystic Fibrosis
Cystic fibrosis, a hereditary disorder affecting the respiratory and digestive systems, leads to the production of thick and sticky mucus that obstructs airways and ducts. Gene therapy aims to deliver functional copies of the faulty CFTR gene into affected cells, enabling them to produce normal mucus and improving lung function.

Beta-thalassemia, a blood disorder characterized by reduced or absent hemoglobin production, causing anemia and complications, seeks to introduce functional beta-globin genes into bone marrow cells via gene therapy. This enables the production of healthy red blood cells.

Sickle Cell Disease
Sickle cell disease, resulting from a mutation affecting hemoglobin, causes misshapen red blood cells prone to clumping, leading to pain and organ damage. Gene therapy aims to modify hematopoietic stem cells to produce corrected hemoglobin, preventing the formation of sickled cells.

These groundbreaking advancements underscore the immense potential of gene therapy as a transformative tool in addressing a broad array of genetic disorders and diseases. As ongoing research continues to push the boundaries of scientific understanding, the future of gene therapy holds unparalleled promise in revolutionizing approaches to medical treatment.

Video 5: Gene Therapy for blindness (YouTube, 0:58)
Video 6: Individualized Drugs & Gene Therapy (YouTube, 8:58)

Participate in Trial

Are you a patient and considering to participate in a clinical gene therapy trial? Your doctor may be an excellent resource to help identify clinical trials for a particular disease. There are a number of online resources that can also assist in locating clinical trials that are accepting patients:

When looking for a clinical trial, remember to make sure the trial is appropriate for the disease. Most trials also specify an age range for the participants. Additional eligibility requirements must also be met, but these will vary depending on the individual study. Contact the health professionals if they are not listed. It is always best to discuss these issues before you travel to gene therapy center. More clinical trial information.

Be aware that Gene Therapy Net is not intended to replace or constitute the giving of medical treatments or advice.

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