Gene therapy is the modification of a person's genes to treat or cure a disease. It is done through different mechanisms, such as: replacing the diseased gene with a healthy one, inactivating the gene causing the disease or introducing a modified gene into the body. This therapy is also studied to treat cancer as well as genetic and infectious diseases.
For neurodegenerative diseases, in which most conventional drugs have not worked, gene therapy is a promising area to be investigated. One of the most important challenges in the clinical application of these therapies is to find drugs that are safe and capable of crossing the blood-brain barrier. Many studies have been carried out over the past decades with different types of gene therapy, and most have focused on genetic diseases, such as spinal muscular atrophy, frontotemporal dementia and Huntington's disease.
Currently, research is focusing on identifying new viral vectors. These are viruses, modified so they can longer cause disease, which are used as vehicles to deliver therapeutic genes to human cells. Transgenic strategies are also an object of study. These are based on designing nucleic acids (part of the genetic material) so that they interact with the genes that cause the disease. The best administration route for these drugs is also being investigated, whether intravenous, intrauterine or intramuscular, for example.
According to a review published in the journal, Nature Neuroscience, viral vector-based gene therapy has shown promising results in spinal muscular atrophy. This has led to research in the treatment of other neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's disease. Spinal muscular atrophy is a genetic disease that causes damage to motor neurons, a type of nerve cell in the spinal cord and lower part of the brain, that controls the movement of the arms, legs, face, chest, throat and tongue. In most cases, the cause of the disease is the deletion of the SMN1 gene, which codes for the SMN protein. The US FDA (Food and Drug Administration) recently approved three gene therapies that increase the levels of the SMN protein and improve the symptoms of patients with spinal muscular atrophy.
Alzheimer's and Parkinson's: unfinished business for neuroscience
Meanwhile, Alzheimer's, which affects 50 million people worldwide, is perhaps the clearest example of a neurodegenerative disease with very few therapeutic alternatives. Gene therapy is also being investigated for this, although many clinical trials with small molecules and antibodies have so far been disappointing. The treatments approved to date only provide mild symptomatic relief. However, many efforts are being made to find treatments capable of modifying the course of the disease. In fact, a study of a drug (not based on gene therapy) was published recently, which seems to reduce the accumulation of amyloid plaques; however, much more research is needed to prove its efficacy.
Gene therapy has also been considered for treating Parkinson’s. This is the most common neurodegenerative disease after Alzheimer's. Current treatments offer only symptomatic relief with significant side effects, and do not stop progression. Thus, it is believed that gene therapy can help to restore the imbalance of the neurotransmitters altered in Parkinson's disease and improve neuronal survival, by modifying the genes directly related to the disease.
Gene therapies are promising because they could represent a significant change in the treatment of inherited and sporadic neurodegenerative diseases, for which there is currently no cure. However, there are still many challenges to overcome until these therapies can be applied.
information documented by:
Dr Raquel Sanchez-Valle, head of both the Neurology Service and the IDIBAPS Alzheimer's Disease and Other Cognitive Disorders Group; and Dr Sergi Borrego, neurologist at the Alzheimer's and Other Cognitive Disorders Unit.