In the last decade, a group of researchers from the University of Auckland’s Centre for Brain Research developed a sheep model for Huntington’s disease. They did this in the hope that it would help to reveal what happens to the brain in the pre-symptomatic stages of the disease. For these kinds of brain disorders damage happens long before the person starts showing symptoms, and in most cases it’s too late to fix the problem once symptoms have started to appear. The ideal treatment would fix the problem at the very beginning, so that as little damage occurs as possible, or even better, prevent the disease process from beginning in the first place. Huntington’s disease is special, unlike other neurodegenerative diseases you can be diagnosed decades before problems start to occur, so the opportunity for treatment is huge. We just haven’t been able to pin down a way to treat it. But this group of researchers may have just cracked it.
What they’ve found is increased urea, and urea transporters, in the brains of these sheep. Why is this important? Because urea, and the ammonia that usually goes alongside it, is incredibly toxic to cells. If there’s a build up of urea and/or ammonia, then cells start to die, and we know that there is massive cell death in the brains of people with Huntington’s disease. There is a chance that this excessive amount of urea and ammonia could be the driving force behind the cell death we see in Huntington’s disease. If that’s true, then a treatment that targets urea could be incredibly effective.
It’s unclear if the brain just isn’t able to clear the urea like normal, or if it’s producing far more urea than it should be. The toxicity of urea means that it’s usually very tightly controlled by your body, being moved away from vulnerable cells and sent to kidneys as quickly as possible. The increase in urea transporters suggests that the brains of those with Huntington’s disease are trying to clear urea, but aren’t able to do this fast enough and so there’s this build up occurring. We’ve seen this in post-mortem brains of people who had Huntington’s, but this new research shows that this process isn’t a side-effect of cell death; it’s a potential cause. It may not be the only cause of cell death and other symptoms of Huntington’s, but it is a huge step toward an effective treatment for the disease.
The best part? There are already drugs available to treat uraemia’s (disorders where urea builds up in the blood due to poor kidney function). The team are now testing some of those drugs on their sheep, to see if they work to prevent the development of Huntington’s. If they do then we could see a treatment available in months to years, instead of decades. It might not be a cure, there is no way to tell right now, but it is the biggest leap forward we’ve had in decades. Not surprisingly, one of the researchers leading the work is Professor Russell Snell who was part of the team who identified the Huntingtin gene in 1993. Hope can be hard to find in the face of a disorder like Huntington’s disease, but there are people out there who have dedicated their lives to fighting for that hope. And now, for the first time in decades, it really looks like hope might just win after all.
Read more about the work Russell and his team are doing with HD sheep here:
https://www.ncbi.nlm.nih.gov/pubmed/26864449 - metabolic changes in HD sheep
https://www.ncbi.nlm.nih.gov/pubmed/29229845 - Brain urea changes in HD patients and HD sheep