A caregiver has asked me, as CurePSP’s Chief Clinical Officer, to list the most important clinical research advances in PSP of 2023. Happy to oblige. Here are my top five in no particular order.
- The FDA approved a combination of two drugs called taurursodiol and sodium phenylbutyrate with the brand name “Relyvrio” for use in amyotrophic lateral sclerosis (ALS; Lou Gehrig disease). A trial in PSP has already started to recruit patients. The drugs address an issue in the mitochondria shared by the two diseases in different sets of neurons.
- Tau PET ligand APN-1607 received go-ahead from the FDA to proceed to a pivotal Phase 3 trial. Such a trial began recruitment in December in the US and will involve multiple other countries as well. The compound would allow a diagnosis of PSP in early or equivocal cases by being taken up by the abnormal tau protein in the brain and imaged.
- A drug called TPN-101 was found to be safe and well-tolerated in a Phase 1 trial of 30 patients with PSP. The drug counters inflammation in the brain by reducing the transcription of ancient viral DNA in our genome. Next is a small trial for efficacy.
- A simple, remote, gait-monitoring system with only three sensors proved able to distinguish the gaits of PSP and PD. Further testing for its ability to document progression or improvement will follow.
- PET imaging of frontal lobe synapses showed good correlation with the PSP Rating Scale and with the results of cognitive testing. This is different from typical PET in neurodegenerative disease, which images glucose utilization or protein aggregates. The work suggests that synaptic imaging could be a good diagnostic marker in the earliest, pre-symptomatic stages of PSP.
But the most important piece of news is that several drug companies are planning to start clinical treatment trials in the next year or two. I’ll report on all that as it happens.
PSP Blog 
Dr. Golbe-
I was pleased to see the recent announcement that the ORION trial is moving forward & has commenced recruiting at U.S sites. The recruitment criteria specifies that patients have a confirmed or probable diagnosis of PSP Richardson’s type. Are you in a position to clarify whether this would exclude patients with other subtypes of PSP (eg. PSP-P)? Thanks much for your hard work.
Sorry, but people with non-Richardson PSP subtypes are excluded. The problem is that it’s too difficult to say with degree of certainty necessary for research that what looks like PSP-Parkinsonism isn’t actually MSA-Parkinsonism or an atypical case of Parkinson’s disease.
I’m trying to clarify these categories. My husband’s neurologist described his case as PSP, and also Parkinsonism, as well as atypical Parkinson’s. He responds positively to levodopa. I have your PSP book, but I’m still unclear. H
Mayo, you’re not the only one who finds these terms confusing. “Atypical Parkinsonism” (not “atypical Parkinson’s”) refers to any disease that causes the combination of signs and symptoms called “Parkinsonism” (i.e., some combination of slowness, stiffness, tremor and balance difficulty) other than Parkinson’s disease itself. There are about 60 or 70 such diseases, the most common of which are PSP, CBD, MSA and DLB. So, “Parkinsonism” isn’t a disease, but a combination of the signs and symptoms I listed.
The subtype of PSP called “PSP-Parkinsonism” can look a lot like Parkinson’s disease, especially early in its course, including having a useful response to levodopa.
Does this imply that the drug may not be effective for other phenotypes of PSP, or does it indicate that they cannot accurately measure results for other phenotypes?
In some cases, neurologists may not provide any phenotype information, so it is unclear what the criteria are in such instances.
Thanks for asking that, abhay.
There’s no reason to think the drug would be more effective for some PSP subtypes. The main reasons to exclude people with non-Richardson from the trials are:
1) The “primary outcome measure” for the trials, the PSP Rating Scale, was developed for and validated on people with PSP-Richardson’s.
2) The diagnostic criteria for PSP-Richardson’s are more accurate than for the other types, which can produce false-positive diagnoses of PSP. Allowing people with non-PSP into the trial would reduce the ability of the trial to detect an anti-PSP effect if the drug has one.
3) Some of the other non-Richardson subtypes, especially PSP-Parkinsonism, the second-most-common subtype, progress about much more slowly than PSP-Richardson. This produces statistical “noise” for a study designed to assess a slowing in the rate of progression by the study drug. It also slows the average rate of progression for the patients in the trial as a whole, which means that a trial of the standard 12-month duration is less likely to be able to answer the question. That means that the trial has to be either larger or longer. Either way, it means it’s more expensive and a longer trial delays the FDA approval process. That means a shorter patent life for the drug.
As for your last comment: While the neurologist referring the patient to the trial may not know the phenotype (i.e., the subtype), the doctor at the study site would be able to determine it by applying the formal criteria published in 2017.
Thank you for clear and detailed explanation Dr. Golbe.
Dr. Golbe:
So do you suppose she is diagnosing him with PSP-Parkinsonism? We would like to pursue the latest diagnostic avenues in the articles you cite, even recognizing the uncertainty involved. My question is where can one go to pursue them? The Cure PSP cites do not associate doctors with such specifics. Thank you! M