Gene Therapy for Monogenic Inherited Disorders.

BACKGROUND: New gene therapy approaches have emerged as promising treatment options for rare congenital disorders and certain tumor entities for which previously only procedures of limited curative potential had been available, if at all.
METHODS: Based on a selective literature search, the principles of gene therapy, the current status of clinical application, and the methods and results of gene therapy approaches are discussed.
RESULTS: In vivo gene therapy relies mostly on the use of vectors based on modified adeno-associated viruses to introduce a functioning copy of the missing or defective genetic information into the target cells. In ex vivo gene therapy, the target cells are extracted, genetically modified using a viral vector, and then returned to the patient. Predominantly lentiviral vectors are used for this purpose. With regard to monogenic disorders, gene therapies are available for the treatment of patients with severe combined immunodeficiency (ADA-SCID), congenital retinal dystrophy (RPE65 mutations), transfusion-dependent β-thalassemia, and spinal muscular atrophy. In spinal muscular atrophy, for example, single-dose in vivo gene therapy leads to progress in motor development that could not be expected to occur in the natural course. These effects are particularly pronounced when the gene therapy is administered before the onset of symptoms.
CONCLUSION: The first gene treatments have now been approved and bring hope of long-term therapeutic benefit after a single administration. The numbers of patients who come into question for specific therapies are often low, so that many different aspects- generation of evidence on efficacy and safety, determining indications, performance of the treatment, pricing-bring new challenges.