Designing treatments that stop protein clumping

There are currently no treatments that are able to slow or halt toxic processes in the diseases that cause dementia, and so efforts to identify new ways to tackle these diseases are paramount. Many forms of dementia are characterised by the clumping of toxic proteins, so preventing this build-up could be a key strategy to disrupt the toxic chain of events. This project encompasses the important early steps along the road to potential new treatments for dementia.

Clumps of toxic proteins are found in the brains of people with dementia, and in Huntington’s the protein in these build-ups is called htt. Scientists know that build ups of htt trigger toxic processes within nerve cells, therefore disrupting the clumping of htt could prevent these damaging cascades from being initiated. Prof Harm Kampinga and his team in Groningen have discovered a protein, called DNAJB6, that can disrupt the clumping of htt, and if they are able to design drugs to boost this protein, this could represent a new way to tackle Huntington’s disease, for which there is currently no treatment

The team already know that DNAJB6 can prevent the clumping of htt, but so far they have studied this protein using genetic methods. Now they need to find out whether it is possible to design experimental drugs that can boost the levels of DNAJB6. They will work to establish new experimental systems in which they can detect changes in DNAJB6, which they can then use to screen hundreds of experimental compounds to see if any have the desired effect. They also want to understand more about how DNAJB6 works to bring about its effect on htt, as it may be easier to boost the activity of the protein rather than boosting the levels of the protein itself. Once the team has performed these vital early investigations into DNAJB6, they will pass on the project to the Alzheimer’s Research UK Drug Discovery Alliance. The DDA has dedicated expert teams of biologists and chemists working to design new treatments for dementia, who can progress the project through the next stages of development. Projects such as this one lay the crucial foundations upon which treatments of tomorrow can be built.