On the 25th of July around 40 doctors and scientists from the UK and around the world met at Queen Square in London. I went along with Sian Alexander – Academic neurology trainee, researcher on clever cellular stuff and an accomplished baker of cakes (catch her on twitter @siankalexander). This meeting was a poignant echo of the diseases under discussion, coming 50 years after the first description of ‘Richardson’s syndrome’, or Progressive Supranuclear Palsy (PSP) as we know it today. The meeting covered cutting edge research in PSP and its cousin Corticobasal Degeneration (CBD). Below are some thoughts from me and Sian on the day.
At the end of the day I was left encouraged, but with a touch of disappointment. There was a hint of disappointment that two big trials in PSP had failed to show any impact on the disease. However, this is not a field where people shrug their shoulders and sit back. There was a palpable sense of optimism. The two trials had shown that it can be done. Yes, the first bites at the cherry have failed, but doing it all again is not so daunting, partly thanks to a newly formed national network of centres in the UK studying PSP and CBD. The PSP Association should take credit for raising the profile of the disease, not only amongst the general public but also for cajoling, arm twisting and, more importantly, funding researchers to take on the challenge. I overheard an American visitor who was astonished how much money the PSP Association had managed to put together to fund research and care, far outstripping their American counterparts per head of population.
To take a more in-depth view, we’ll break the sessions down and give you a feel for the main headlines from each. The range of talks and work show-cased impressed me. Although a few themes recurred throughout the day, each talk was unique and the cast was stellar in terms of reputation and quality.
The first session covered ‘basic science’, although as my brother continually reminds me there is nothing basic about it. The day kicked off with two household names from the world of dementia research. Michel Goedert takes an interest in how proteins build up in the brain, and particularly the tau protein that causes problems in PSP and CBD. He is firmly of the opinion that tau is responsible for the disease rather than being a by-stander, showing compelling evidence that tau protein travels from cell to cell through the brain causing mischief. John Hardy followed with an update on the genetics of the tau protein. He also talked about Genome Wide Association studies in PSP, trawling genetic information from people with the disease to look for clues that might push someone a few percent towards or away from getting the disease. The results so far point to 3 processes where damage occurs: integrity of nerve connections (synapses), the electrical insulation of nerves (myelin sheath) and brain cells’ response to damage (the so-called ‘stress’ response). An intriguing talk from Steve Gentleman discussed dementia pugilistica, something that hit the news in the past week in rugby players. Although the link between head injury and PSP/CBD is far from certain and dementia pugilistica is quite different from either disease, there are similarities in how the brain appears under the microscope. This line of research promises to throw up some intriguing clues in the future.
Human disease biology came before lunch covering lumbar puncture, new brain imaging techniques and brain pathology. At the moment these tests remain very much in the research arena and for the moment do not add much to the diagnosis, but are starting to show promise in tracking the changes of disease over time. A promising new tool on the near horizon is a dye injected in the blood stream that clings to tau protein in the brain making it visible with a PET brain scanner. The usefulness of this sort of scan will need to be tested, but it sounds like we are getting close to something usable.
The most eagerly anticipated session came just after lunch, discussing therapeutics. I’ve previously written about Davunetide, and unfortunately both Tideglusib and Sodium Valproate disappointed in their results. Although, as one Alzheimer’s researcher pointed out, at least they didn’t make people worse as many of the recently tried drugs have for that disease. David Burn took us through a post-mortem of these trials. Reassuringly, the researchers involved in these studies were keen to share their data with him and are due to publish their results soon. This will help greatly in working out what went wrong and planning future studies. Hugh Nutall from the drug company Eli Lily had the trickiest talk of the day, trying to predict where PSP/CBD therapies will be in 5 years’ time. He talked about a number of promising compounds in development, many attacking the tau protein but in a different manner to previous efforts. It remains to be seen which will make it through to full blown clinical trials.
A particular step forward in clinical trials design has been the PSP rating scale, developed by the legendary Larry Golbe who was at the meeting. It is being widely used, enabling better assessments of how individuals with PSP respond to trial medicines.
The final session started with talks covering some good old-fashioned clinical questions of diagnosis and syndromes. The Queen Square Neurology department have been at the fore-front of sub-classifying PSP, CBD and similar diseases. It was a particular pleasure to have John Rohrer talk, a neurologist and researcher in frontotemporal dementia – another disease where the tau protein builds up in brain cells. Even though us doctors might make a diagnosis of one or the other disease in the comfort of our clinic rooms, real life teaches us that under the bonnet there may be something very different going on. This is a challenge that will become increasingly important to solve if the treatments we develop only address a single disease process. In addition, picking up the earliest signs of PSP or CBD is extremely difficult, and other than spreading information about these diseases among GPs and neurologists, perhaps that is one challenge that no one came up with a good answer for.
To conclude the day, Larry Golbe led a discussion about funding priorities in PSP, who funds what research, and whether the research priorities are the right ones. The mission statement of the PSPA “Working for a World Free of PSP” was undisputed, but there was lots of ground for discussion about the best way to go about doing this. It was a thought-provoking way to end an enjoyable and educational day.