Therapy Analysis - Gene therapy - Still the Next Big Thing?
A look at the state of gene therapy
The first approved gene therapy procedure was performed in 1990, on four year old Ashanti DeSilva, who suffered from the rare genetic disease severe combined immunodeficiency (SCID). At the time, and even to this day, gene therapy was often touted as the 'next big thing', holding the potential to effectively treat previously unmanageable diseases. However, as is so often the case, the obstacles to such a powerful technology were perhaps underestimated and today, almost 20 years later, there is still limited application of gene therapy outside of the experimental setting.
To date, and with the aid of the Human Genome Project, over 4,000 genetic diseases have been identified. These are a result of single-gene defects (also called Mendelian or monogenic disorders), mutations in multiple genes (multifactorial), chromosomal abnormalities, or occasionally mutations in the nonchromosomal DNA of mitochondria.
Normal pharmacological treatment of disease seeks to correct aberrant biochemistries in the body via the proper application of agents to counteract these problems. Gene therapy however, goes one step further, and actually acts upon the root cause of target diseases - correction of the 'faulty' DNA itself. This is achieved via the insertion of a functional copy of one or more of the defective genes into a patient's cells to produce a missing or damaged protein, reintroducing it into the aberrant biochemical pathway and effectively fixing the disorder. Genes are delivered into the patient using a vector, most commonly retroviruses, adenoviruses, adeno-associated viruses and herpes simplex viruses, which have been genetically altered to carry human DNA and integrate these genes into the host DNA. Non-viral vectors such as oligonucleotides and liposomes are also potential vectors for this process. Other approaches, aside from the basic gene replacement aspect, include knocking out mutated genes or introducing new genes into the body to help fight a particular disease.
Gene therapy therefore holds an incredible potential in the treatment of genetic disorders. Much like the field of stem cell therapeutics it represents an entirely new paradigm in human healthcare, not just 'treating' disease, but actually repairing the underlying cause of the disease to eradicate it altogether. It was hoped that this revolutionary therapy would provide a platform to successfully treat not only rare genetic disorders caused by single-gene defects, such as phenylketonuria , SCID and Duchenne muscular dystrophy (among many others), but also more complex multifactorial diseases such as cancer and AIDS. However, much like the aforementioned area of stem cell research, translating the principles of such a technology into actual therapies for everyday use has proved significantly harder than perhaps was originally thought. The number of successful gene therapy applications is still small enough that any new one is still very much a significant step forward.
