Research into a cure for Huntington’s disease (HD) is currently mainly focused on the following areas: reducing production of the destructive mutant form of the protein that causes the disease; understanding what makes certain nerve cells in the brain vulnerable, in order to help them survive HD’s harmful effects; and replacing lost nerve cells.
The HD gene encodes for (instructs the body to produce) a destructive mutant form of the protein huntingtin.
Research into the kind of gene therapy known as gene silencing is aimed at turning off the encoding action and thus reducing production of mutant huntingtin. Gene silencing experiments in mice have shown that when production of the protein is reduced, symptoms improve. Gene silencing has now also been demonstrated in non-human primates.
A new kind of gene therapy that is currently causing great excitement among scientists is CRISPR: this technique uses a defence mechanism discovered in bacteria that “snips out” the defective part of a gene and replaces it with the normal gene sequence.
Improving nerve cell survival
Scientists are studying the process of nerve cell death that occurs in the brains of patients with HD. Research into this includes:
– Investigating why the nerve cells become “overexcited” by natural brain chemicals.
– A defect in the mitochondria, the energy-generating “powerhouse” of the cell.
– Production of toxic compounds in the brain called free radicals.
– Natural chemical substances in the body that may protect against cell death.
– Understanding more about the losses of nerve cells that transmit and receive information.
Stem cell therapy: replacing lost neurons
Stem cells are the unspecialised cells found in a developing embryo (in the very early stages) that eventually become the specialised cells of all the different tissues in the body.
With regard to Huntington’s disease, scientists are hoping to replace damaged nerve cells by transplanting stem cells into affected areas of the brain, where they will hopefully develop into new cells.
Experiments have yielded mixed results using this technique in animal models and preliminary human clinical trials. One of the challenges is getting the nerve cells not only to grow, but to form proper connections. Even though stem cells are not ready to be used to treat Huntington’s disease yet, these investigations are greatly improving the understanding of HD.
Drugs being tested for potential treatment of HD include those that may help control symptoms, slow disease progression, and correct the chemical imbalances in the brain that contribute to the development of HD.
Several drugs have shown promise in animals, including creatine, coenzyme Q10 and the antibiotic minocycline. Some of these have been tested by humans in clinical trials, but none has been proven effective yet.
Observational studies of human volunteers with HD are helping scientists better understand the neurobiology of HD and design parameters for future clinical trials.
– Genetics Home Reference, U.S. National Library of Medicine, National Institutes of Health. HTT. http://ghr.nlm.nih.gov/
– National Institute of Neurological Disorders and Stroke. Huntington’s Disease: Hope Through Research.