Current clinical trials

As always, at your service.

Here’s an updated list of current and possible future clinical trials that I know of for PSP. For more information, visit and in the search box, enter the ID number in the first column. If you’re interested in joining an observational study (i.e., one not involving treatment), those are listed on the website as well.

clinicaltrials. gov IDDrugSponsorPhaseMechanismLocation(s)DosingComments
noneSodium selenateGov’t of Australia2Enhances dephosphoryl-ation of tau by protein phosphatase 26 sites in AustraliaOralRecruiting
NCT 04734379FasudilWoolsey2aRho kinase inhibitorUCSFOralCompleted recruiting; Study to end in 11/2023.
NCT 04993768TPN-101Transposon2aReduces tau productionBoca Raton, FL, Farmington Hills, MI, Las Vegas, NV, Gainesville, FL, Englewood, COOral30 patients on drug, 10 on placebo; completed recruiting; completion 7/2023
NCT 04937530RT001 (di-deuterated linoleic acid ester)BioJiva (product from Retrotope)2aReduces lipid peroxidation, enhancing mitochondrial activityUniversity of Munich (Germany)OralNon-controlled study showed very slow PSP progression over 2 years.  Small RCT results due in 11/2022.
NCT 04539041NIO-752Novartis1Anti-sense oligonucleotide; reduces tau productionRochester MN, Nashville TN, La Jolla CA, Boca Raton FL; 2 in Montreal; 5 in Germany; 1 in UKInfusion into spinal fluid at lumbar spaceStill recruiting; 4 injections into spinal space over 3 months. Completion in 5/2024.
NCT 04008355AZP2006AlzProtect1Reduces phosphor-tau by enhancing progranulin3 sites in FranceOral solution~24 patients on drug, `12 on placebo
noneAtomoxetine (brand: Strattera)Cambridge University2aFor mood disorders of PSPCambridge, UKOralNoradrenaline for Progressive Supranuclear Palsy Syndromes (NORAPS).  Contact
NCT 04468932TMS in PSPOregon Health & Science U, Portland; NIHNATranscranial magnetic stimulationPortland, ORNon-invasive magnetic fieldRecruiting; Expected completion: June 2026
NCT 04014387Suvorexant and zolpidemUniv of California, San Francisco4Two approved sleep aids never before evaluated in PSPAll evaluations are remoteOralCompletion expected May 2024. No need for patient to travel to research center. The expected benefit is in sleep, not movement.
NCT 03924414Zoledronic acidCalifornia Pacific Medical Center Research Institute4Anti-osteoporosis drug to prevent fractures in neurological diseases with falling55 locations, all in the USOne intravenous infusionCompletion expected Nov 2023.
May start recruiting in the next year: 
?ASN120290Asceneuron1Reduces tau misfolding and aggregation by inhibiting O-GlcNAcase? Press release info only
?MP201Mitochon1Mitochondrial decoupler? Early in planning per press release
?Tolfenamic acidNeuroTau2NSAID that reduces tau productionCleveland Clinic, Las Vegas + others?  

We can dream, can’t we?: An unscientific survey

Here’s a hypothetical question for you all:  How effective does a neuroprotective drug have to be for you to want to use it?

What prompted this question is the recent FDA approval of a new drug to slow the progression of ALS (Lou Gehrig disease).  It gives the patient, on average, 25% more survival time.  Now, suppose a drug to slow the progression of PSP provided the same benefit?

The average person with PSP received the correct diagnosis about 3½ years after the first symptoms appear and, with currently available treatment, die an average of 4 years later.  So if a new drug slowed the progression by 25% and is started immediately after the diagnosis of PSP is made, then that 4 years becomes 5 years – not much of an improvement, but better than nothing.

The cost of Relyvrio for ALS is $158,000 per year.  The cost of Aduhelm, which was approved last year for slowing the progression of Alzheimer’s disease, is $28,000.  Let’s say our hypothetical PSP drug splits this difference, at $93,000.  We don’t know how much of that would be covered by the various drug insurance plans, and of course, not everyone has drug insurance. 

Let’s assume that the hypothetical PSP drug has no important side effects and that it requires a monthly intravenous infusion lasting 2 or 3 hours.  (Some of the experimental PSP drugs are just oral pills and one is an injection every 3 months into the spinal fluid, as for a spinal tap.)

So, my question boils down to this:  Would you opt to receive this PSP drug with a 25% slowing benefit – or not?  The benefit to the average patient would be one more year of survival – more for some, less for others. 

A point in favor: The drug wouldn’t just prolong the final year, when the person is most disabled.  Rather, it would prolong each year of those 4, so that the first year’s mild level of disability would persist for 15 months rather than 12, and so on.

Two points against: 1) You’d have to take the drug for the rest of your life, or until something better came along. 2) Future participation in a clinical trial of a potentially better drug might not be allowed for people already on another PSP-protective drug.

Any thoughts for my highly unscientific survey would be appreciated.  Click “Leave a comment” just below this line.  Feel free to explain your thinking.

Genetic testing advice

I’ll plagiarize myself again. CurePSP asked me to write up a piece in response to someone asking if a person with PSP or CBD (or suspected PSP or CBD) should have genetic testing. The short answer is mostly “no,” but here are the details:

People with an established diagnosis of PSP or CBD and a close relative with one of those conditions (or a strong suspicion thereof) should consider having their MAPT gene sequenced.  That’s the gene encoding the tau protein.  But the vast majority of those with PSP or CBD have no similarly affected relatives, and for them, genetic testing is neither necessary nor useful.

The test should sequence the entire MAPT gene and not merely check for the ten mutations, all of them very rare, that have been associated with PSP (seven with CBD) in the past.  If the person with the disorder (called the “proband”) proves to have a mutation in MAPT, then other family members with similar symptoms can be tested as well. 

Variants in eight genes other than MAPT have been associated with PSP and five with CBD, but each of these raises the disease risk only slightly and testing for them is not useful in an individual or even in a family.  That’s because these are only “marker associations,” not specific mutations altering a protein known to be involved in the PSP process. The markers are called “single-nucleotide polymorphisms” or “snips” and unlike the MAPT mutations, they incriminate a span of about 100 or so genes, not a specific gene, much less a specific mutation that can be tested for.

We must keep in mind that many mutations, even in genes like MAPT, are harmless and do not cause disease.  Sixty MAPT mutations have been reported in humans so far, and only ten of them are known to cause PSP. So having a mutation in MAPT and having PSP doesn’t necessarily mean that one caused the other.  If a relative with the same symptoms has the same mutation, it may still not be cause-and-effect, but if that relative is distant, or the proband and two or more relatives share symptoms and a mutation, then the likelihood of cause-and-effect is greater. 

Even if there’s a good statistical likelihood that the proband’s mutation is the cause of their disease, and a healthy relative proves to have the same mutation, one still would not be able to predict how soon the relative might start to develop symptoms.  That information could be available soon from some other type of “pre-symptomatic” or “predictive” testing, but no such test has yet proven to be sufficiently accurate in such a situation.

People with suspected PSP or CBD with no relatives with similar symptoms have no need for genetic testing.  Even if one of the known PSP/CBD-causing mutations were found, it would not contribute much to the likelihood of PSP or CBD as the diagnosis explaining the symptoms.  The same is true for the healthy relatives of someone with established PSP/CBD.

So, as you can tell, estimating disease risk from genetic testing can be complicated.  That’s why a professional genetics counselor or a physician with expertise in adult neurogenetics should advise anyone considering having family genetic testing for PSP or CBD. Don’t just rely on the simple report supplied by 23andMe.

I’ll update this as necessary.

Let’s talk about paw-paw.

Rousting me out of my recent blog-post drought was some click-bait I saw about the growing popularity of a fruit called paw-paw.

The paw-paw fruit with its seeds

So-named because of its outward resemblance to papaya, paw-paw grows on trees both wild and cultivated, in the eastern US and Canada.  The flesh is sweet and creamy, like a banana, and can be consumed in many forms.  Maybe the only reason it’s not more popular is that the fruit is easily bruised during shipping.  It’s one of the faves of the locavore, farm-to-table movement in eastern North America.  So, what’s not to like?

Here’s what: Paw paw contains a mitochondrial toxin called “annonacin.”  It’s not only on the seeds, leaves and roots, where toxins exist in many plants with harmless fruit, but also in the fruit itself.  The toxin inhibits the action of “complex I,” a critical part of the process in the mitochondria that makes energy from sugars and oxygen.  It seems likely that the toxin serves the plant as a defense against insects, whose mitochondria, like ours, are susceptible to it.

Annonacin first reached the attention of scientists studying neurodegeneration after the 2002 publication of a description of a tauopathy endemic on the Caribbean island of Guadeloupe.  A third of the people with that disease met diagnostic criteria for PSP. The others had falling, frontal cognitive loss and disinhibited emotional responses, but not the eye movement palsy of PSP.  Compared with people on Guadeloupe with typical Parkinson’s disease or healthy controls, those with “Guadeloupean tauopathy,” as it came to be called, were far more likely to have consumed a tropical fruit called soursop. You guessed it: soursop turns out to have harbor annonacin, like paw-paw.

Prompted by that information, scientists in Germany injected annonacin intravenously into rats.    The result was a tauopathy that resembled PSP in the rats’ motor behavior and in the appearance of their brain cells under the microscope. The same group subsequently found that annonacin can cause tauopathy by a very different mechanism as well.

Shortly thereafter, I did a dietary risk factor survey among my patients with PSP, comparing them to controls with non-degenerative neurological diseases from our clinic.  So few had ever eaten paw-paw (or soursop) that the study didn’t have the statistical power to answer the question and I never published it.  (The more common foods included in the questionnaire gave no statistically significant results, either, in case you were wondering.)

Bottom line: There’s probably not enough annonacin in paw-paw to cause PSP or other tauopathies after only occasional consumption.  But over decades?  And what about people with a genetic predisposition to develop tauopathy?  Or people who just love paw-paw and eat them like candy? (There are some!) I think more research and some careful thinking by the FDA is needed before paw-paw becomes more widely marketed and consumed alongside apples, bananas and oranges.