Yearly Archives: 2022

Genetic testing advice

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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.

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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.

Lecanemab for Alzheimer’s: “Proof of Principle” for PSP

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I’m not above plagiarizing myself. What follows is a piece I just wrote for the CurePSP website. It’s pitched at a simpler level than most of my blog posts, but it’s close enough. As I learn more about this drug, I’ll fill in some technical details for you.

Great news for people with Alzheimer’s disease:  A monoclonal antibody for intravenous infusion called “lecanemab” has been found to slow the rate of worsening of early-stage AD by 27%.  The Japanese drug company Eisai, which developed the drug, and the US company Biogen, which is assisting in the testing, jointly announced the news on September 26.  If approved by the FDA, lecanemab would be the first drug available to slow the underlying disease progression in AD rather than merely treating the symptoms, as Aricept and other existing drugs for AD do.

In almost all neurodegenerative diseases, one or more proteins forms clumps called “aggregates” in brain cells.  Lecanemab is an antibody directed against beta-amyloid, which is one of the two proteins that aggregate in AD.  The other such protein is tau, which of course is the one protein that aggregates in PSP and CBD.  In MSA, the protein is alpha-synuclein.  Beta-amyloid protein is not involved in PSP, CBD or MSA.  Two different monoclonal antibodies directed against the tau protein have failed to slow progression in PSP.  Nevertheless, the lecanemab news is welcome for people with PSP, CBD and MSA.  Here’s why:

  • This is the first demonstration that reducing levels of the aggregating protein in a neurodegenerative disease can actually slow the ongoing progression of the condition in humans.  (This has been accomplished in many ways in lab animals, but their artificial versions of human brain diseases are very incomplete models.)  This means that some other way of reducing tau protein in humans with PSP/CBD might work.
  • The two monoclonal antibodies that have failed in PSP were directed against the same end of the tau protein (called the “C-terminal” or “microtubule-binding domain,” if you want to get technical).  Other monoclonal antibodies directed against the other end of tau (the “N-terminal”) might work better, especially as fragments of tau that include the N-terminal now seem to be the bad actors.  Such monoclonal antibodies are in early-phase testing.
  • Until now, it has not been fully clear that in human neurodegenerative diseases, the aggregating protein is what’s causing the loss of brain cells.  Competing theories suggest that something else is damaging the brain cells and the protein aggregation is merely a result of that process rather than its cause.  The lecanemab news suggests that the aggregates themselves are to blame.  This makes future drug development a lot easier and more focused.
  • Although no monoclonal antibody trials are currently in progress for PSP, CBD or MSA, there is a current trial of another way to reduce tau protein.  Rather than destroying protein as antibodies do, this approach prevents the offending protein from being manufactured in the first place.  It’s called “anti-sense oligonucleotide” treatment, and an early-phase safety trial for PSP is under way at several sites in the US and elsewhere.  Trials of other ASOs for other neurodegenerative diseases are planned.

So, we congratulate the AD world on this successful trial, which we hope and expect will be the first of many, and we take heart that this “proof of principle,” as scientists call it, can soon be applied to PSP, CBD and MSA.

More fun than a spinal tap

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A diagnostic tool routinely used in psychology is the Rey-Osterreith Complex Figure:

The patient is timed while copying the figure.  The figure and copy are removed and the patient re-copies the figure from memory immediately and again after 30 minutes.  It’s a sensitive measure of visuospatial recall, visuospatial recognition, response bias, processing speed, and visuospatial constructional ability.

Although the test has existed in its current form since 1944, there has been no publication on its utility in PSP.  Now, an Italian research group at the University of Pisa led by Dr. Luca Tommasini gave the test to 30 people with PSP-Richardson syndrome, 30 with Parkinson’s disease and 30 healthy persons matched to the others on age, gender and educational attainment. 

It was previously known that people with Parkinson’s make errors on the test related to planning and impulsivity.  The new study found that in PSP, those errors are more severe than in Parkinson’s, with the added problems of disinhibited repetition of some elements and “vertical expansion” of the figure.  The latter could be related to the difficulty in moving the eyes vertically or to an underlying difficulty in accurately conceptualizing vertical space.  In my own experience with people with PSP, there is disproportionate difficulty attending to objects and events at the upper and lower extremes of the visual space even if the eyes were still able to move adequately in those directions.

These results could help distinguish PSP-RS from PD diagnostically.  We await results for the other disorders with which PSP can be confused such as multiple system atrophy-parkinsonism and corticobasal degeneration.  We also await results from very early-stages of the disease, when such a diagnostic test would be most useful, and from variant forms of PSP such as PSP-parkinsonism and PSP-progressive gait freezing, where cognitive abilities are not usually as impaired as in PSP-Richardson syndrome.

Anti-sense oligo update

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CurePSP asked me to write up something on ASOs for their website (www.curepsp.org). Thought I’d give my loyal blog readers a sneak peak:

Probably the single biggest story in the world of PSP right now is NIO752.  That’s an antisense oligonucleotide (ASO) being tested for safety and tolerability in people with PSP.

ASOs interrupt the process by which a specific gene’s DNA is transcribed into RNA, thereby reducing the production of the encoded offending protein.  The ASO itself is a short stretch of RNA whose genetic code is a mirror-image of part of the DNA whose translation is to be suppressed.  The ASO’s genetic sequence and that of the offending DNA recognize each other and stick together, preventing the corresponding protein from being produced. In this case, the targeted DNA is the MAPT gene, which encodes the tau protein. Other ASOs operate by targeting slightly different stages of the transcription/translation process.

In the US, the FDA has approved several kinds of ASO, the best-known being nusinersin (brand name “Spinraza”) for spinal muscular atrophy, a progressive and usually fatal condition that typically starts in infancy but in mild forms can start at any age.  In the pivotal trial of nusinersen, 21 of 51 infants receiving the drug were improved after 6 months, while that was true for none of the 27 infants receiving sham treatment.  If we can achieve similar results for NIO752, it would be by far the best news ever for PSP.

ASO molecules are too large to cross the blood-brain barrier, which means that for a brain disease, they must be administered by injection directly into the spinal fluid.  This is performed as for a diagnostic spinal tap.  In the current trial, NIO752 is given once monthly over a period of 3 months and the participants are examined periodically for an additional 9 months.  The 64 participants are at 4 sites in the US (La Jolla, CA; Boca Raton, FL; Rochester, MN and Nashville TN), 2 in Canada (both in Montreal), 5 in Germany and 1 in the UK. This safety and tolerability trial is expected to end in May 2024.  Its sponsor is Novartis Pharmaceuticals, co-headquartered in Basel, Switzerland and Cambridge, MA. For more information: 1-888-669-6682 or novartis.email@novartis.com

A trial can detect important safety issues with only 64 participants but detecting actual benefit requires more.  The standard “primary outcome measure” for clinical treatment trials in PSP is the PSP Rating Scale.  Assuming that is still the case in 2024, when a treatment trial would begin, and half of the participants receive placebo, the minimum number of participants needed would be 276.  That number also assumes that the study is designed to detect at least a 30% difference between the two groups’ rates of progression.  Detecting less of a difference would require more participants and detecting a greater difference would require fewer.  A new outcome measure with less variability than the PSPRS would reduce the number of participants required.

From the standpoint of those with PSP and their families hoping to enter a trial of NIO752, the most important number isn’t a number, but a date: A trial starting in mid-2024 would probably end in 2027. Another important number is the eventual price of the drug.  NIO752 would have to be injected every month, lifelong. Nusinersen’s price is $125,000 per injection.  So, if the price of NIO752 is anything like that, the cost to Medicare, Medicaid and private insurors would present an impossible situation.  CurePSP estimates that about 20,000 people in the US have PSP at any given time.  If even half of them received a $125,000-per-month drug, the total annual cost would be $15 billion plus the doctors’ fees for the monthly injection procedure.  Clearly, something would have to give. 

But first, let’s hope that NIO752 actually works.

Executive dysfunction, as it were

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A major announcement: There’s now evidence that an important factor in the cause of PSP are variants in two “regulatory genes” called PLEKHM1 and KANSL1, both of which are very near the MAPT (tau) gene on chromosome 17. 

Regulatory genes are not encoded into protein.  Rather, they affect the rate at which other genes are transcribed into protein, kind of like business executives or military officers directing the activities of others.  Such proteins are called “transcription factors.” The project identified the gene being regulated in this case as SP1, which encodes the protein called Sp1 (note the lowercase p; the fewer abbreviations in science, the better, I always say). SP1 is located on chromosome 12 and works in tandem with a group of other genes to regulate many cellular processes. 

As a comparator, the researchers used samples from people with Alzheimer’s disease, finding that it involved a different set of regulatory genes that did not interact with SP1.  This result could allow drugs that regulate the Sp1 protein or gene-directed therapy for the PLEKHM1 or KANSL1 genes to be developed as treatment or prevention for PSP. The new finding’s significance is underscored by its publication in Science, one of a small handful of top general scientific journals. 

The research was a collaboration between the highly productive neurodegenerative genetics groups at UCLA and UCSF, with Drs. Daniel Geschwind and Martin Kampmann, respectively, as senior members.  The first author was Yonatan Cooper, an MD/PhD student at UCLA.  In response to my email, Yonatan commented, “A key challenge in modern medicine has been interpreting genetic risk factors [for diseases of complex causation] and translating them to understand disease mechanisms. This is especially true for the 17q tau locus, which is the major genetic risk factor for PSP.  The approach that we used was crucial to allowing us to identify these new genes in that region.” 

The “approach that we used” in Yonatan’s quote is called a “massively parallel reporter assay” (MRPA).  It assesses thousands of single-nucleotide DNA variants for their ability to regulate other genes’ protein expression levels.  For this study, the researchers chose the region close to the two variants in or near the MAPT gene found in 2011 by the PSP Genetics Consortium and funded by CurePSP.  That region comprises hundreds of genes, any of which could be actual source(s) of the PSP risk in that region of the genome.

That 2011 study used “single-nucleotide polymorphisms (SNPs)” in DNA from autopsy-confirmed PSP brain tissue and control subjects.  Even now, 11 years later it remains the most informative single study on the genetics of PSP.  (Disclosure: I was a minor co-author.)  It identified a handful of regions across the genome where a marker differs between the two groups, implying that a gene near each marker contributes to the cause of PSP.  Two of those markers were in or near MAPT.  But that technique can’t positively incriminate which of the hundreds of genes in that region of chromosome 17 actually cause(s) the disease.  The current study did that by testing all of the thousands of variants in those genes for their ability to alter protein production in a way that could help cause PSP. 

One next step is to look for drugs or other treatments to counter the effect of these two regulatory abnormalities on the function of the SP1 protein and/or a protein with which it interacts.  Another next step is to use the same technique to look for other regulatory genes near the other PSP-related markers identified in the 2011 SNP study and more recently and to look for drug targets in the protein products of the genes they regulate.

I don’t know about you, but I’m nerdy enough to be very excited about this!

Thinking out loud

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I’m making a list of clinical topics to be covered in CurePSP’s next annual scientific conference.  That task made me think carefully about what’s important to clinicians seeking to stay current on PSP and CBD.  So, I thought I’d share that list with you all, for what it’s worth.  Keep in mind that the laboratory research end of things will be a separate list.

  • Clinical spectrum and its pathology
  • Clinical aspects of genetics and epigenetics
  • Fluid biomarkers             
  • PET biomarkers
  • MRI biomarkers
  • Clinical outcome measures (rating scales, wearables, eye movement, gait measures, etc)
  • Gene therapy
  • Tau-directed drug trials
  • Mitochondria-directed drug trials
  • Gait retraining
  • Current best practices in symptomatic care

Plug and play

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My last post was about an on-line tool to assist in reading MRI scans to differentiate PSP from some other diagnostic possibilities.  But the formal diagnostic criteria for PSP are still based on traditional history and neurological exam, with MRI as a confirmatory adjunct. This post is about an on-line tool to assist physicians in using those formal criteria.

Starting in the 1980s, a number of researchers, including me, published diagnostic criteria for PSP.  Although these were later validated by autopsy results, they were not so at the time of publication.  Just as important, they tended to be either insufficiently sensitive or insufficiently specific (see my preceding post for definitions of those).  You want sensitivity if you’re trying to measure the prevalence of the disease and don’t want to miss any cases.  You want specificity if you’re trying to recruit a group of people with PSP for a study of causes or treatments and don’t want to risk including anyone without actual PSP.

So, in 1986, Dr. Irene Litvan, now at UCSD, then at the NIH, organized an international group of leading PSP experts to create new criteria.  They produced two sets for living patients: “possible PSP” was more sensitive and “probable PSP” was more specific.  “Definite PSP” was reserved for autopsy-confirmed cases, and the project also included a new set of criteria for that, which served as the “gold standard” by which to validate the first two. 

The new sets were called the NINDS-SPSP Criteria after the National Institute of Neurological Disorders and Stroke (the part of the NIH involved) and the Society for PSP (the former name of CurePSP), which provided a grant for the project. 

The NINDS-SPSP criteria were a hit and remained the world’s standard until researchers realized that those criteria took no heed of the clinical variants of PSP that were starting to be described in 2005.  The classic form of PSP now received the name “PSP-Richardson syndrome” after the leader of the group in Toronto who first described the disease in 1963.  It turns out that PSP-RS explains only about half of all PSP!  The most common of the newly-described variants is PSP-parkinsonism, accounting for about 25% to 40% of all PSP.  Six other much less common ones have been reported, each of which starts with and emphasizes one of the features that starts later in the course of PSP-RS.  Towards the later stages, all of the variants acquire most of the classic features of PSP-RS and all tend to look the same by that point. 

Sorry for that digression.

So in 2015, Dr. Guenter Höglinger, then in Munich, now in Hannover, convened a group to devise a new set of criteria to tease out the different types of PSP and to identify PSP in its earliest stages.  Of course, there aren’t yet enough autopsied cases to provide the stastistical power needed to validate their criteria for the less common PSP types, but that’s changing.  In any event, the new criteria were published in 2017 and dubbed the “MDS PSP Criteria” to recognize the support of the Movement Disorder Society.

Click to access nihms879447.pdf

Just one problem: they’re very complicated, occupying 7 pages of tables in the journal. To remedy that, Dr. Hoglinger and colleagues have created an on-line form that performs the same diagnostic algorithm as all those tables.  It’s free and it’s at https://qxmd.com/calculate/calculator_567/diagnosis-of-progressive-supranuclear-palsy-psp  I’d suggest that you try it out, but many of the data fields require the results of a neurological exam performed by an experienced neurologist.  Furthermore, many of the questions ask things like whether the patient has any evidence of certain alternative diagnoses, and that’s not something that a layperson is likely to know.  But feel free to forward the link to your favorite neurologist for their use.  The different PSP subtypes have different rates of progression, so identifying one’s subtype could be useful.

Mail-order diagnosis

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You may have noticed that I’ve been bullish on the ability of ordinary MRI scans to help diagnose PSP.  Now there’s an on-line, automated resource to allow anyone anywhere to upload MRI images and receive an answer – for free.

We’ve known for over a decade that very careful, standardized measurement of the size of various parts of the brain can track the progression of PSP over the 1-year course of treatment trial better than the PSP Rating Scale or any other “bedside” measure.  But more recently, MRI has been found to be highly useful in the differential diagnosis of PSP – that is, telling PSP from normal aging, Parkinson’s, Alzheimer’s, and other conditions. 

For an excellent, technical, open-access review of simple MRI measurements in the diagnosis of PSP, click here. The leading authors are Dr. Aldo Quattrone and his son Dr. Andrea Quattrone at Universita Magna Graecia in Catanzaro, Italy, who pioneered most of the discoveries described.

Such MRI-based measurements use only routinely obtained images like those from your local radiologist.  But actually doing the measurements requires some experience.  The Catanzaro group has created a Web portal onto which anyone can upload de-identified MRI images from a CD.  An answer returns in a few days.  The site is https://mrpi.unicz.it/. 

The black-and-white images below show the inputs into the automated algorithm.  Sorry if these close-up brain images look like abstract expressionism.  The drawings here may help orient you.

MRI images A and B are sagittal (A is in the midline and B is a few mm to one side), images C and D are in the coronal plane and image E is in the horizontal (or axial) plane.

from: Quattrone, et al. Brain Science, 2022.

A: midbrain area (upper outline; Amb) and pons area (lower outline; Apons) (In PSP, atrophy of the midbrain is marked but atrophy of the pons is mild.)

B: middle cerebellar peduncle diameter (This atrophies only a little in PSP.)

C: superior cerebellar peduncle diameter in a slice parallel to the midline (“parasagittal” slice; This atrophies moderately in PSP.)

D: third ventricle diameter (averaging the diameters of the front, middle and back thirds) (This enlarges markedly in PSP.)

E: maximum distance between anterior horns of lateral ventricles (This atrophies moderately in PSP.)

The number derived from these measurements is called the magnetic resonance parkinsonism index (MRPI).  Its value is (Apons/Amb) x (B/C).  Values above 13.88 indicate PSP-RS with 89% sensitivity*, 95% specificity* and 94% accuracy*. This works best in separating PSP-Richardson syndrome from Parkinson’s disease. 

The MRPI 2.0 is (MRPI) x (D/E).  This works better than the original MRPI in separating PSP-Parkinson and other non-Richardson PSP variants from Parkinson’s disease.  Values above 2.70 indicate PSP with 86% sensitivity, 92% specificity and 90% accuracy.

*Sensitivity is the fraction of people with the disease who have a positive test. 

Specificity is the fraction of people without the disease who have a negative test. 

Accuracy is the fraction of people with an accurate test, whether positive or negative. 

In this case, “the disease” means PSP and “without the disease” means PD, some other disease or no disease.

The really valuable part is that this technique works well even in early, mild cases, where a diagnosis could not be made by other means.  In a few studies, such patients were followed for years until they showed more definitive signs, which were then used to validate the initial, image-based diagnoses.

This technique has not been shown effective in differentiating PSP-P from multiple system atrophy of the parkinsonian type (MSA-P), which is a common dilemma for movement disorder specialists seeing a patient with mild symptoms.  But the MRPI and MRPI 2.0 could be combined with other supplementary tests such as supine and standing blood pressure (usually abnormal in MSA-P, normal in PSP) and still-experimental tests such as blood levels of tau, phosphorylated tau and neurofilament light chain (all elevated in PSP, not in MSA) to refine its abilities.

Another important caveat:  Sometimes PSP can be mimicked by rare cases of common diseases like Alzheimer’s or dementia with Lewy bodies, or by some rare diseases like corticobasal degeneration, frontotemporal dementia with parkinsonism, or pallidopontonigral degeneration.  There haven’t yet been enough patients with those things subjected to the MRPI or MRPI 2.0 to prove those formulas able to separate those conditions from PSP.  After all, the MRI only looks for atrophy of certain brain structures, regardless of whether that atrophy is related to tau aggregation or something else.

Bottom line:  As my medical students don’t appreciate hearing, no diagnostic test short of autopsy is ever going to be definitive on its own.  Any test will have to be combined with old-fashioned history and exam and with other imaging, fluids or physiological tests.  Knowing which of those to choose for a given patient and how to interpret the results will keep humble, human neuro-diagnosticians in business for a while longer.

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In my next post: another on-line tool for the diagnosis of PSP.

Sleep treatment study seeks participants

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One of the top PSP research centers in the world is at the University of California San Francisco.  Two researchers there, Drs. Christine Walsh and Thomas Neylan, are leading a study of sleep in PSP and asked me to help them find suitable participants.

The goal is to test the effect of two sleep medications on the treatment of sleep disruption in PSP.  No in-person visits to San Francisco are required and no study staff would need to come to your home. 

Both medications, zolpidem (Ambien) and suvorexant (Belsomra), are approved by the FDA for sleep in general, but their benefit and side effects in people specifically with PSP remain unclear.  This study uses a crossover design so that each participant will receive the two medications and placebo over the 6-week course of the study. Sleep will be monitored by questionnaire and by two small, wearable devices to record movement and brain waves, respectively. All of the questionnaires will be done over the phone or by Zoom, with 1 to 3 calls each week for 6 weeks.

Participants must have a diagnosis of PSP, live anywhere in the United States, and have an available care partner to help provide information during the interviews.

You can find more information about the study by viewing a video here: https://pspsleepstudy.com or by emailing Dr. Walsh at: Christine.Walsh@ucsf.edu. Click here for the listing in clinicaltrials.gov.