This could be the best news ever in the history of clinical drug development for PSP.
Last week, I attended the Global Tau meeting in London as a representative of CurePSP. Plenty of excellent research was presented, but most of it was laboratory work that would be difficult to relate to the direct concerns of most of this blog’s readers. But there were some clinical advances, and here’s a big one.
Dr. Adam Boxer of the University of California, San Francisco is the project leader for the PSP Trial Platform (PTP). My Oct. 27, 2023 post briefly mentioned that the PTP had just been funded by the NIH. A trial platform is an organization, in this case about 50 study sites throughout North America, that invites multiple pharmaceutical companies to simultaneously allow it to test their trial-ready experimental drugs. The big news last week was Dr. Boxer’s announcement identifying the first two drugs and that enrollment should begin in late 2025.
One drug to be tested will be AZP-2006, from Alzprotect, based in Lille, France. It addresses tau accumulation and neuro-inflammation. The other is AADvac1, from Axon Neuroscience, based in Bratislava, Slovakia. It is an active vaccine directed against the tau protein. More on those drugs in a future post. Both will be Phase 2a trials, meaning that the emphasis will be on safety and tolerability, though efficacy will be detectable if it’s dramatic. The PTP has a candidate for a third company/drug in the wings awaiting final contract negotiations.
The double-blind phase for each drug would be 12 months, followed by an open-label phase, where the participants on placebo will be offered active drug. The primary efficacy outcome measure will be a version of the PSP Rating Scale abridged from its original 28 items to the 15 items best suited to daily disabilities.
Advantages of platform trials over traditional single-drug trials:
• Only one central coordination, technical and statistical staff is needed. This makes drug testing more economical in terms of both money and time, lowering the bar for smaller companies to test promising treatments.
• Only one placebo group is needed and more active-drug arms can be added in the future. So, if a traditional trial offers only a 50% chance of receiving active drug, a platform trial testing three drugs would offer a 75% chance of being assigned to active drug.
• Once the platform is up and running, there is no delay for test site recruitment, contracting and training. This further reduces the costs and allows a new drug to be smoothly slotted into a vacated spot.
• It’s possible to make the three drugs’ trial protocols relatively uniform, allowing the results to be compared with greater confidence than would be possible if each had been tested in separate projects.
• The availability of a completed control group facilitates an interim analysis (a peek at the incomplete data under strict confidentiality rules) to determine if continuing that drug’s trial would be futile. If the result is unfavorable, this saves time, money and most important, drug side effect risk for future participants. Such a drug could be withdrawn from the PTP and another drug could take its place.
The other Principal Investigators working with Dr. Boxer are Dr. Anne-Marie Wills at Massachusetts General Hospital, Dr. Irene Litvan at UC San Diego and Dr. Julio Rojas of UCSF. The NIH has committed $70 million over five years to this project and the participating drug companies would also contribute substantially (though much less than if they had mounted trials on their own). Dr. Boxer told me that as of last week, in late April 2025, the NIH funding had not been affected by the recent Federal research budget cuts, but we’re all holding our breath on that.
PSP Blog 
This is great news! Thanks for the update
Jim
Dr. Golbe-
Great to have you back writing again & wonderful news on the platform trial. I’m sure you have heard the announcement about the new skin biopsy test for PSP out of of U. of Toronto. I’d be curious to know your thoughts on a couple of questions. Although they were able to clearly differentiate Parkinson’s & PSP patients because of the different proteins involved (a-synuclein vs. 4R-tau), they didn’t include any Alzheimer’s patients in the study. Based on the similar tau pathology, do you think their test would distinguish PSP from Alzheimer’s? They also included some MSA & CBD patients but reported that only some of these biopsies were positive which kind of leaves me puzzled. Thoughts appreciated. Thanks
Dear Mr. Swanson:
To answer your first question, I’ll bet that the researchers at the U of Toronto didn’t include Alzheimer’s samples in evaluating the skin biopsy diagnostic test for PSP because there’s never been a case of someone with autopsy-proven AD who looked like they had PSP during life.
As for your second question, one of the 18 participants with MSA had a biopsy positive for tau. They included that disease, a synucleinopathy, in the group because it can outwardly resemble PSP closely, especially in the early stages. Only two of the five participants with CBS were positive for tau, which may seem disappointing, but keep in mind that there’s a sample size issue there, and a few patients with CBS actually have non-tauopathies such as vascular disease or FTLD-TDP43. Also, it’s possible for Pick’s disease, which is a type of FTLD with 3-R tau, to produce a CBS appearance outwardly, and the biopsy was designed to look for 4-R, not 3-R tauopathy.
Bear in mind that these numbers are small, so the percentages could change as more patients are analyzed. Also bear in mind that the diagnoses of PSP, MSA, CBS, etc in this study were only clinical, not autopsy-based. Furthermore, they were sufficiently advanced to have satisfied standard clinical diagnostic criteria. We don’t know how well the skin biopsies would do if administered to people in the early, equivocal stages of their conditions, and if the researchers wait until autopsies are available to calculate the results.
Dr. G
Hi. My father has Parkinson’s disease, what do we need to do to volunteer for this test?
Hi. Unfortunately, there is no test yet. The research I describe is more a “proof of principle.” It shows that different genes work together to increase one’s risk of PSP to a level beyond what merely adding those genes’ risks would suggest. Perhaps in a few years we will have what’s called a “risk panel” for PSP, but it will require more data on more genes than this paper provides.