A breakthrough has been made in the treatment of Huntington’s disease at University College London. For the first time, researchers have been able to correct the disease in patients. Potentially, the new treatment could be a cure for the devastating neurodegenerative disease.
Huntington’s disease is incurable and fatal. Once symptoms of the disease are first noticed, patients typically only survive between 10 and 20 years. Most patients start to experience symptoms of the disease in their 30s and early 40s. There are approximately 8,500 patients in the UK that have been diagnosed with the disease, while a further 25,000 patients are known to have an error in the huntingtin gene that means they will develop the disease in the future.
The huntingtin gene is responsible for the production of a protein called huntingtin, which is essential for brain development. The error in the huntingtin gene results in the production of damaged proteins, which cause the death of brain cells, ultimately reducing patients to a vegetative state.
Genetic editing techniques such as CRISPR-Cas9 have potential to be used in the treatment of Huntington’s disease, although the technique is still in the early stages of development. At University College London they used a different method to silence the huntingtin gene.
The drug kills the mRNA that would otherwise trigger the synthesis of damaged huntingtin proteins. The researchers injected the drug into the spinal cords of patients and were able to reduce the number of damaged huntingtin proteins in the brain. The drug was also well tolerated by patients.
Lead researcher and director of the Huntington’s Disease Centre at UCL, Prof Sarah Tabrizi, said, “For the first time we have the potential, we have the hope, of a therapy that one day may slow or prevent Huntington’s disease.”
The drug cannot be seen as a cure for Huntington’s disease, as the long-term effects of treatment are not known. Patients will need to be monitored over time to determine how effective the treatment is, although studies in animal models suggest that the treatment can change the course of the disease. Some of the animal research studies saw motor function recover.
There is hope that by using the drug on patients that carry the DNA defect, but are yet to develop symptoms of the disease, those symptoms can be prevented from occurring.
Protein Identified That Regulates Embryonic Stem Cell Development
Further research that could lead to a new treatment of Huntington’s disease and various other neurodegenerative diseases has also been published recently. Researchers at the Cologne University’s Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases (CECAD) have discovered a protein that helps to regulate embryonic stem cells and the transformation into mature nerve cells.
While it has been possible to generate mixtures of neuronal and other cell types, until now it has not been possible to differentiate stem cells into neurons efficiently; however, the Cologne researchers have discovered a method that allows the differentiation of embryonic stem cells into mature neurons with 100% efficiency.
The researchers discovered that embryonic stem cells have high levels of a protein called CSDE1 compared with mature neurons. Using CRISPR, they were able to deactivate the gene responsible for generating production of that protein. Doing so resulted in the stem cells differentiating into neurons.
“By silencing one single protein with the gene-editing method CRISPR, the cells spontaneously start to differentiate into neurons! That’s a great and much faster way to increase neurogenesis,” David Vilchez, PhD, principal investigator at CECAD and senior author of the study.
Hyun Ju Lee, lead author of the study. “We also double-checked in multiple stem cell lines from different donors and induced pluripotent stem cells and got the same results.”
The ability to grow neurons could prove invaluable in the study of a wide range of diseases such as Huntington’s Parkinson’s and Alzheimer’s.
The research paper – A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation in human embryonic stem cells – was recently published in Nature Communications.