Three more encouraging reports from the Neuro 2023 conference jointly sponsored by CurePSP and the PSP Association of the UK, held in London on October 19 and 20.
- In a series of 48 people with corticobasal syndrome (CBS) during life who had brain autopsies, the underlying pathology was actually corticobasal degeneration (CBD) in 16 (33%), PSP in 14 (29%), Alzheimer’s disease in 6 (13%) and other conditions in the rest. Similar results have been found many times before, but this study analyzed the neurologists’ office notes and found that actual CBD pathology was most likely in patients with gait freezing as one of the first symptoms. Among those without early freezing, CBD was most common in those with no early speech problems and onset before age 66. Those with PSP pathology tended to have had early speech difficulty and onset after age 61. These observations could be useful to neurologists in separating CBD from PSP during life for purposes of prognostication and treatment trial enrollment. (Ikuko Aiba, et al., Higashinagoya National Hospital, Japan)
- In 2018, the TRIM11 gene on chromosome 1 was identified as the location of a variant influencing the onset age of PSP, but the precise molecular mechanism underlying that effect remained unknown. Now, researchers have teased out a single nucleotide variant in an intron (a section of the gene regulating the rate of manufacture of the protein it encodes rather than its amino acid sequence) of TRIM11. They found that the protein encoded by TRIM11 tags abnormal tau for degradation by the 26S proteasome, which is one of the cell’s garbage disposal systems, and that the variant reduces the production of that protein. This means that somehow stimulating TRIM11’s expression (the rate at which it encodes its protein) could slow the spread of abnormal tau and the progression of PSP. (Sumi Bez et al, University College, London, UK)
- The drug ezeprogind (previously called AZP2006) has shown favorable results in an early-phase test for safety in people with PSP. The trial was too brief and small to establish efficacy, but the sponsor, Alzprotect of Loos, France, notes “very promising trends” in slowing progression of the disease. The orally-administered drug works by reducing inflammation and by improving the action of the lysosomes, one of the cell’s garbage disposal mechanisms. It will now enter a 120-patient efficacy trial using slowing of progression on the PSP Rating Scale after 12 months as its primary outcome measure. Half of the 24 trial sites will be in the US and half in Europe. A start date has not been announced. (Noelle Callizot, et al, Alzprotect, Loos, France)
PSP Blog 
I had never heard of PSP until my mother was diagnosed with it about 3 years ago. Before she was diagnosed with PSP, we all thought it was dementia and Alzheimer’s. She passed away this June, and watching your loved one go down, and she went down in hurry the last 3 months of her life. She went to a better place than here on earth, but it still hurts, and hurts like hell. But know that she isn’t suffering anymore gives me some peace, but I miss her so bad. I was cleaning the room that she stayed in at my house this weekend and opened a tote, and it had some of her clothes in there and I could smell her. I broke! I have yet been able to grieve the loss of her, I try to stay busy, so my mind doesn’t have time to think about how she suffered and how scared she was of dying. That is what hits me in the gut. I still hear her say, “Misty, I am scared, I don’t wanta die”. We did have hospice at the house, to help, but I thought that when it was getting to the very end that we would have someone with us most all the time to help. This is such a nasty and hurtful disease that I wish there was more that I could have done for her. I feel like I could have done more, should have done more. But there is always those should I have, would have’s that go through your mind. RIP- Momma, I will always love you, never forget you and forever will be your baby girl.
Dear Ms. Cook:
Thank you for the heartfelt description of your and your mother’s PSP journeys. It’s clear how difficult her illness was for both of you.
With several clinical treatment trials about to start and with the success of similar treatments, albeit modest, in Alzheimer’s disease and ALS, we have more reason than ever to believe that disease-slowing treatment for PSP is only a couple of years away. Until then, sharing our feelings about the disease could be the most important way to deal with it, and I thank you for your willingness to do that here.
Dr. Golbe
Thank you, Dr. Golbe, for continuing to provide such useful information about PSP. It is SO valuable and well-presented. It is VERY appreciated.
Redvolca: I appreciate your saying that and am glad to be of some help.
Do you have insights as to where the trial locations for AZP2006 might be located?
No, I don’t. Amylyx asked me for some recommendations, which I provided, but they haven’t told me their decisions.
Is there any possibility of being considered for the trial (PSP patient based in the UK)?
Juliet —
Just some background for everyone: You’re talking about: company: Amylyx; trial : ORION; drug’s generic name: AMX 0035 or taurursodiol; drug’s brand name: Relyvrio.
My latest information is that the trial, which is up and running in the US, will eventually start in Europe and Japan. But I’m not sure if any of the European sites will be in the UK.
Keep an eye on:
https://clinicaltrials.gov/search?cond=Progressive%20Supranuclear%20Palsy&term=orion
for the latest official information from Amylyx, which will include contact information for prospective participants.
Amylyx had originally planned for the European sites to start later this yards, but the company has had to cut back financially, which could result in delays or maybe even reduction in the number of sites of the ORION trial.
Relyvrio was approved for ALS in 2022 on the basis of a Phase 2 trial, but after a Phase 3 (i.e., larger) trial reported in March 2024 of this year showed no benefit, they had to withdraw it. That was their only revenue-producing drug, so they’ve had major staff cutbacks, which I assume would slow everything down for them.
https://www.fiercepharma.com/pharma/amylyx-pull-failed-als-drug-relyvrio-market-cut-70-staffers
But as far as I can tell, Amylyx remains committed to the ORION trial.
LG