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It was interesting to see that Tideglusib might be useful for slowing atrophy rates in Progressive Supranuclear Palsy (PSP), see here. So I thought I should offer a few of my thoughts on the very small amount of information available. Firstly, I think they’re taking the right approach given what we currently know. Tideglusib is supposed to target GSK-3, an enzyme that stops the phosphorylation and aggregation of tau protein. The debate rages on as to whether tau is truly involved in the pathology of PSP and other dementias  (similar to the amyloid beta debate in Alzheimer’s, but a few steps behind). My gut feeling is that, like beta amyloid, tau will play a small role in disease but is more likely to be the tombstone of more complex underlying changes in metabolism.

I am not at all surprised, and would have been incredibly sceptical, if they had met any clinical endpoints in this study. Once the symptoms of any dementia (PSP included) have taken hold the disease has probably been ongoing for many years and the processes within the brain are on a roller-coaster downhill track and it will be very difficult to even slow them down, never mind stop them.

I thought I would be more excited about the reduced rates of atrophy. The brain shrinks as we get older, referred to as atrophy. In dementia this process is accelerated, and in PSP the midbrain in particular really shrinks away very rapidly. The main parts of the brain that cause problems in PSP are the midbrain and the frontal lobes. Unfortunately the article doesn’t mention the frontal lobes at all, leading me to think they didn’t find any significant effects there. The only sensible conclusion I can see is that the drug slows down atrophy in parts of the brain largely unaffected by the tau tangles that characterise PSP and that the drug is supposed to target. I don’t know if there was a control arm, it would be interesting to see whether the drug would have the same effect on healthy individuals as well.

So, in summary, I think (but I’m not sure) the drug is the right sort of drug to be using. But I’m not convinced yet this is the right drug. I would love to be proved wrong, but there’s more work to be done yet.

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