Gene Therapy: The Next Frontier in the Treatment of Genetic & Rare Disease.

Gene therapy is the use of genes as treatment for a genetic disease by directing the expression of a therapeutic protein or restoring the expression of a missing protein. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual to repair a faulty gene copy or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. This approach is different from traditional drug-based approaches, which may treat symptoms but not the underlying genetic problems.

The scope of this approach is broad and promising for a wide number of diseases including inherited disorders, some types of cancer, and certain serious viral infections.

There are two main types of gene therapy: Somatic gene therapy and Germline Therapy. In the former, only somatic cells (body cells) are targeted and not the germline cells (gametes or sex cells). In this case, the altered genome only effects the treated individual and not any offspring. Germline therapy involves incorporation of a tailored gene into the gametes, permanently altering the genes inherited by future generations. This type of therapy is prohibited in many countries due to ethical, technical concerns and due to the lack of extensive scientific research.

There are multitude of challenges involved in developing a successful gene therapy. The condition in question must be well understood and identification of the underlying faulty gene is crucial. The specific cells in the body that requires treatment must be identified and accessible. More importantly, the most suitable vector (a vehicle/carrier) for efficient gene delivery must be made available.

The two major classes of methods are those that use recombinant viruses (viral vectors) and those that use naked DNA or DNA complexes (non-viral methods) to deliver a gene to the specific cells. Once its inside, the cell’s gene-reading machinery uses the information in the gene to build RNA and protein molecules. The proteins can then carry out their job in the cells.

Genes can be delivered into a group of cells in a patient’s body in two ways. The first, called in vivo is to inject the vector directly into the patient, aiming to target the affected cells. The second, ex vivo, is to deliver the gene to cells that have been removed from the body and are growing in culture. After the gene is delivered, integration and activation are confirmed, and the cells are put back into the patient. Ex vivo approaches are less likely to trigger an immune response, because no viruses are put into patients. They also allow researchers to make sure the cells are functioning properly before they’re put in the patient.

Gene therapy was first conceptualized in 1972. The first FDA approved experiment in humans was in the early 1990s to treat ADA-SCID. Since then, numerous clinical trials have been underway with successful treatment of patients with the retinal disease Leber’s congenital amaurosis, ADA-SCID, Adrenoleukodystrophy, Chronic lymphocytic leukemia (CLL), Acute lymphocytic leukemia (ALL), Multiple myeloma,  Haemophilia and Parkinson’s disease. In 2012, Glybera® became the first gene therapy treatment to be approved for clinical use in United States and in the Europe, for adult patients diagnosed with familial lipoprotein lipase deficiency (LPLD) confirmed by genetic testing, and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions.

Gene therapy hence, offers the possibility of a potentially curative benefit to patients with genetic diseases. There has been a flurry of activity in this space with few players like GSK, Uniqure, Bluebird Bio and Celladon leading the way. Although this approach is still largely an experimental discipline, much research is underway in certain conditions to realize its full potential. One must not ignore as well, the cost implications surrounding gene therapy.