This article describes gene therapy of various neurodegenerative disorders: Parkinson disease, Alzheimer disease, Huntington disease, and amyotrophic lateral sclerosis. Some of these are in clinical trials. Parkinson disease is an ideal candidate. The introduction of functional genes into the brain of patients with Parkinson disease may, for example, prove useful for replacing a defective gene, introduce a potentially neuroprotective or neurorestorative protein, or permit the physiological delivery of a deficient neurotransmitter. Gene editing enables repair of a defective gene in vivo. Potential gene therapy approaches to Alzheimer disease are based on neurotrophic factors and not neurotransmitters. The optimal method of gene therapy is ex vivo involving implantation of genetically engineered cells secreting nerve growth factor. A clinical trial for amyotrophic lateral sclerosis was conducted with implantation of genetically modified cells secreting a neurotrophic factor.
Historical note and terminology
Gene therapy is the transfer of genetic material to target cells, instead of just the products of cells with altered genes, in a patient for therapeutic purposes. The term “gene therapy” also covers strategies for modification or suppression of gene function as well as transplantation of genetically modified cells for in vivo production of therapeutic substances. Carriers or delivery vehicles for therapeutic genetic material are called vectors, which are usually viral, but several nonviral techniques are being used as well. The term "genetic engineering" applies to the genetic manipulation of living cells, as well as implantation of genetically engineered cells into the living body, which is a form of gene therapy. Neurosurgeons refer to gene therapy as "cellular and molecular" neurosurgery. Gene editing technologies are also being applied for the treatment of neurodegenerative disorders. The history and basics of gene therapy are described in the article on introduction to gene therapy.
Gene therapy of Parkinson disease, Alzheimer disease, Huntington disease, and amyotrophic lateral sclerosis will be described in this article. RNA interference (RNAi)-based techniques, which can be employed to reduce expression of specific genes, hold great promise as therapy for these types of neurodegenerative disorders.