Authors: Lauren Pulling
Researchers from Imperial College London (UK) have developed a protein that could curb activity of the Huntington’s disease (HD) gene, huntingtin, showing promise for new treatments for the disease. In the study on mice, the engineered protein successfully targeted huntingtin and reduced activity for six months: significantly longer than previous studies.
The protein is an engineered zinc finger, which specifically targets mutant copies of huntingtin that cause the typical pathology and symptoms seen in HD. In the new study, published Molecular Degeneration, 12 mice with HD were injected with a single dose of the protein, resulting in repression of the gene for at least six months. Observations of the mice’s brains demonstrated that 77% of mutant huntingtin gene expression was repressed three weeks post-treatment, with this decreasing to 61% after six weeks and 48% at 12 weeks. At 24 weeks, repression was measured at 23%, which the researchers suggest is still of therapeutic benefit.
In previous studies, the team was able to reduce gene activity for approximately two weeks, making this latest development particularly promising. By making small adjustments in the composition of the protein, the period of action was significantly increased. Additionally, the treated mice displayed no harmful side effects.
“We are extremely excited by our latest results, which show a lot of promise for treating Huntington’s disease,” commented senior author Mark Isalan (Imperial College London). “However, while these encouraging results in mice mean that the zinc finger looks like a good candidate to take forward to human trials, we still need to do a lot of work first to answer important questions around the safety of the intervention, whether repeat treatments are effective, whether there might be longer-term side effects, and whether we can extend and increase the benefits beyond six months.”
Sources: Agustín-Pavón C, Mielcarek M, Garriga-Canut M, Isalan M. Deimmunization for gene therapy: host matching of synthetic zinc finger constructs enables long-term mutant Huntingtin repression in mice. Mol. Neurodegener. doi: 10.1186/s13024-016-0128-x (2016) (Epub ahead of print); www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_9-9-2016-13-13-26