Huntington’s disease research news. In plain language. Written by scientists. For the global HD community.
CRISPR-Cas9 is an experimental gene editing technique used to make precise changes in DNA. For the first time, scientists have used this approach to attack the Huntington's Disease mutation in the brain cells of a mouse. Other researchers are refining CRISPR-Cas9 to be more efficient, specific, and safe. It’s still a long way from use in HD patients, but its application in mice is an exciting step forward.
Exciting new studies provide evidence that a particular kind of cellular trafficking goes awry in Huntington's Disease. Specifically, researchers have learned that traffic in and out of the cells control center - the nucleus - breaks down in HD. These findings open up new avenues for HD research.
Huntingtin, the protein responsible for Huntington’s disease, is fundamentally important for fetuses to develop in the womb, but we don’t know yet exactly what part it plays in this intricate process. Normally, neurons start life deep within the developing brain, migrate out to the surface and then make a network of connections with others, but Sandrine Humbert’s group showed that those without huntingtin get stuck, never making it to where they need to go. Neurons with mutated huntingtin are no better than those that lack it completely. However, reintroducing normal huntingtin, or the proteins through which it acts, allows neurons to migrate normally again, offering tantalising new ways to treat Huntington’s disease.
When the ‘healthy’ HD gene functions as it should, one of its many jobs is in the development of normal embryos. Researchers have long assumed that the ‘mutant’ HD gene inherited by people with HD is still able to do this job, since HD patients develop normally and don’t show signs until later in life. A surprising new finding suggests we may have to think carefully about this assumption!
Clumps of mutant huntingtin protein in brain cells are a hallmark of HD, and they build up slowly, occupying more and more cells over time. Recent research in mice shows that the harmful proteins can travel between neurons, setting off a chain reaction that leads to more sick cells and the development of symptoms.
Researchers have found a connection between HD and an energy-regulating protein called PPAR-delta. Giving PPAR-delta a boost with an existing drug was protective in HD cells and mice, but we’ll likely need to research and test it further before it can go to the HD clinic.
Thinking problems in Huntington’s disease take a huge toll from early in the disease. Now, new work suggests that a drug already approved by the FDA to treat another brain disease – multiple sclerosis – may stave off these problems in HD mice. Could these results be real, or are they too good to be true?
When patients participate in clinical trials, there needs to be some type of readout to determine whether the new treatment worked. It’s important to know two key things: What to measure and how to measure it. In the case of HD, these obstacles have vexed scientists and doctors for years. The latest research comes up with a clever new approach to overcome both challenges in a new way. These results could offer a valuable tool to study new HD therapeutics entering clinical trials.
Because brain cell death drives symptoms in Huntington’s disease, these cells steal the spotlight in disease-related research. But new research on the brain's blood supply has uncovered changes in HD that could be making it harder for the brain cells to cope with the disease.