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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.

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: 'Gene Therapy a new tool to cure human diseases'.

Severe Combined Immune Deficiency (ADA-SCID)
ADA-SCID is also known as the bubble boy disease. Affected children are born without an effective immune system and will succumb to infections outside of the bubble without bone marrow transplantation from matched donors. A landmark study representing a first case of gene therapy "cure," or at least a long-term correction, for patients with deadly genetic disorder was conducted by investigators in Italy. The therapeutic gene called ADA was introduced into the bone marrow cells of such patients in the laboratory, followed by transplantation of the genetically corrected cells back to the same patients. The immune system was reconstituted in all six treated patients without noticeable side effects, who now live normal lives with their families without the need for further treatment. (see also Description of ADA deficiency, ADA: The First Gene Therapy Trial, from the National Institutes of Health and SCID.net)

Chronic Granulomatus Disorder (CGD)
CGD is a genetic disease in the immune system that leads to the patients' inability to fight off bacterial and fungal infections that can be fatal. Using similar technologies as in the ADA-SCID trial, investigators in Germany treated two patients with this disease, whose reconstituted immune systems have since been able to provide them with full protection against microbial infections for at least two years.

Patients born with Hemophilia are not able to induce blood clots and suffer from external and internal bleeding that can be life threatening. In a clinical trial conducted in the United States, the therapeutic gene was introduced into the liver of patients, who then acquired the ability to have normal blood clotting time. The therapeutic effect however, was transient because the genetically corrected liver cells were recognized as foreign and rejected by the healthy immune system in the patients. This is the same problem faced by patients after organ transplantation, and curative outcome by gene therapy might be achievable with immune-suppression or alternative gene delivery strategies currently being tested in preclinical animal models of this disease.

Leber's congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life, and affects around 1 in 80,000 of the population. It was first described by Theodore Leber in the 19th century. LCA is typically characterized by nystagmus, sluggish or no pupillary responses, and severe vision loss or blindness. Researchers at Moorfields Eye Hospital and University College London in London conducted the first gene therapy clinical trial for patients with RPE65 LCA. 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).

Multiple gene therapy strategies have been developed to treat a wide variety of cancers, including suicide gene therapy, oncolytic virotherapy, anti-angiogenesis and therapeutic gene vaccines. Two-thirds of all gene therapy trials are for cancer and many of these are entering the advanced stage, including a Phase III trial of Ad.p53 for head and neck cancer and two different Phase III gene vaccine trials for prostate cancer and pancreas cancer. Additionally, numerous Phase I and Phase II clinical trials for cancers in the brain, skin, liver, colon, breast and kidney among others, are being conducted in academic medical centers and biotechnology companies, using novel technologies and therapeutics developed on-site.

Neurodegenerative Diseases
Recent progress in gene therapy has allowed for novel treatments of neurodegenerative diseases such as Parkinson's Disease and Huntington's Disease, for which exciting treatment results have been obtained in appropriate animal models of the corresponding human diseases. Phase I clinical trials for these neurodegenerative disorders have been, or will soon be, launched.

Gene therapy research could result in effective treatments for mesothelioma patients. Although some types of gene therapy are aimed at specific cancers, early studies show promise for mesothelioma treatment. Suicide genes have also been used in clinical trials with pleural mesothelioma patients. While early results are positive, more work is necessary to develop effective gene therapy treatments.

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