Tag Archives: Parkinson’s

It’s awards season (part 1 of 2)

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A couple of weeks ago I posted my curated list of the top 10 PSP-related research developments of 2025.  They appeared in two installments on 12/31/25 (#1-5)

PSP’s Top 10 of 2025: part 1 of 2

and 1/1/26 (#6-10).

PSP’s top 10 of 2025: part 2 of 2

Clearly inspired by my effort, the publication “Parkinson’s News Today” (PNT) has done something similar for Parkinson’s disease, summarizing their 10 most-often-visited (not necessarily the most important) news stories of 2025.  Their article is very well supplemented with links to both basic explanations and to the PNT articles themselves.  Those PNT items link, in turn, to original journal articles and to press releases from drug companies or research institutions.

Top 10 Parkinson’s news stories of 2025

PNT is owned by a for-profit medical communications company and its on-line publication is monetized by advertising, mostly from drug companies.  So be aware that their choice of what’s important may be biased in favor of drug companies’ products and scientific narratives.  No such concrete instances have hit me over the head, but the potential for a conflict of interest is there.  

Armed with that caveat emptor, you can learn a lot from this list, which is numbered from least to most important. Here are my annotations for each item, pointing out the relevance, or lack thereof, for PSP:

#10: Virus long thought harmless may trigger Parkinson’s

The brain tissue in PSP looks very similar to that of “post-encephalitic Parkinsonism” (PEP), which was quite common from the 1920s to 1950s.  Both feature tau-based neurofibrillary tangles and attack the basal ganglia, but PEP is static over decades.  It appears to be a immunologically-based , residual effect of a brain infection called “von Economo’s encephalitis” or “encephalitis lethargica.”  The virus itself has never been isolated or identified.  The disease overlapped, but is different from, the great flu pandemic following World War I.  Otherwise, despite ample search, there’s little to no evidence that any virus can cause PSP.

#9: Scientists develop weekly injectable implant for Parkinson’s treatment

The implant (actually a viscous, intra-muscular, self-injected liquid) provides levodopa/carbidopa (LD/CD) for a week.  Unfortunately, most people with PSP respond little or not at all to levodopa/carbidopa.  However, in those with the PSP-Parkinsonism subtype and few with other subtypes, there can be a useful response for a few months of daily dosing.  While those with PSP who do respond don’t need a long-acting form, avoiding having to take pills could be a major advantage for those with swallowing difficulty.

#8: DBS plus exercising may rewire Parkinson’s brain

The brain, even in older persons, can route its circuits around areas of damage, especially if those circuits are used often.  That’s called “exercise” or “physical/occupational therapy” or just “practice,” (note my sarcasm) and it does work.  This is true in PSP as well as in PD.  But deep brain stimulation (DBS), at least the kind used in PD, does not work in PSP.  That’s because the brain areas that are overactive in PD simmer down in response to DBS.  But in PSP, those areas are part of the degenerative process itself, and are underactive.  But to repeat: Informal physical activity and formal physical/occupational therapy do work in PSP. They should be an important part of the daily routine, assuming that one’s physician decides that any balance problems, osteoporosis, or cardio-pulmonary disorders are not contraindications.

#7: FDA approves bilateral Exablate Neuro treatment for Parkinson’s

Exablate is the brand name for a device that focuses destructive ultrasound beams on those over-active brain areas of PD.  (It usually appears in the literature as “focused ultrasound” or FUS.) So, the idea is same as DBS, but FUS produces a permanent lesion that can’t be adjusted by the doctor based on the patient’s response. But its advantage of FUS over DBS is no hardware in the head, wires under the skin, pacemaker device in the chest, periodic battery changes, or explanations at metal detectors.  Unfortunately, the FUS lesion locations used in PD would not work in PSP, but novel lesion locations could, in principle, be discovered for PSP for problems like balance, speech or cognition.

#6: Dosing starts in trial of anti-inflammatory therapy for Parkinson’s

PNT’s news item reporting the start of this single-center, Phase I trial appeared in March, as their blurb states, but I’ve got an update for you. The drug’s safety and tolerability were satisfactory but trial, with only 30 patient and one month’s observation, was not powered to demonstrate efficacy. The sponsor company, Ventus Therapeutics, has now started a Phase II trial for PD at 23 US sites.  The drug, called VENT-02, targets NLRP3, a receptor protein activated by stress signals in the microglia, the brain’s equivalent of white blood cells.  That could be relevant to PSP, where microglia help spread the abnormal tau protein through the brain and otherwise mediate the brain inflammation of PSP.

I’ll cover items #5 through #1 tomorrow or whenever my week’s chores permit. 

One RNA fits all?

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Maybe I’m streaming too many dramatic TV series these days.  My October 9 post ended in a cliffhanger, teasing an “oddball” molecule that could point the way to neuroprotective treatments for PSP and other neurodegenerative diseases. It’s called “lncRNA FAM151B-DT.” 

Quickly, some background.  The RNA most familiar to us is messenger RNA.  Its length can be anywhere from a few hundred to a few thousand base pairs (the genetic code’s “letters” for a single gene or a fragment thereof). The RNA is constructed (“transcribed”) in the cell’s nucleus from the code in DNA, then scoots out to the ribosomes, where it’s translated into a string of amino acids to build a specific protein.  But only about two percent of the DNA in our genome encodes the kind of RNA for making proteins, called messenger RNA.  Most of the rest, about 75 to 90 percent, encodes RNA that regulates DNA transcription or other cell functions.  A little of that “non-coding RNA” is “micro-RNA,” which has only about 20 to 25 base pairs, and the rest, with over 200 base pairs, is called “long, non-coding RNA.” 

Now I’ll get to the point. A research group at Washington University in St. Louis just published a paper entitled, “A novel lncRNA FAM151B-DT regulates degradation of aggregation prone proteins.”  They used brain cells obtained at autopsy from people who had died with PSP, Alzheimer’s, or Parkinson’s disease.  They also used skin cells from a living person with a form of frontotemporal dementia with Parkinsonism (FTDP), which is caused by a mutation in the tau gene. They transformed those (slightly) specialized skin cells into unspecialized stem cells, then transformed those into highly specialized brain cells.

The lead author of the WashU study is Arun Renganathan, PhD, a staff scientist in the Department of Psychiatry.  The senior author is Celeste Karch, PhD, associate professor of psychiatry. Disclosure: Dr. Karch and I have collaborated in research in the past and she’s a member of CurePSP’s Scientific Advisory Board, which I am honored to chair.

In each of those four disease-specific brain cell cultures, the team found FAM151B-DT reduced relative to control cells and that silencing FAM151B-DT by “knocking out” its gene increased the concentration of whichever protein was aggregating in the corresponding human disease (tau for PSP, AD and FTD-P; alpha-synuclein for PD). The mechanism was a blockage of autophagy, an important component of brain cells’ “garbage disposal” system.  The researchers found that FAM151B-DT serves as a “scaffold” to allow the tau or alpha-synuclein protein and a “chaperone” molecule called HSC70 to interact with the lysosomes, a kind of bubble in the cell fluid containing protein-degrading enzymes.  

A critical piece of the new research is that increasing the cells’ production of FAM151B-DT stimulated that system to dispose of excess tau or alpha-synuclein. That means that FAM151B-DT is the “rate-limiting step” in the process.  As you’d imagine, this suggests that increasing the concentration or efficiency of FAM151B-DT could slow or halt progression of these diseases.  All four of them.

So, how does this relate to the cliffhanger from yesterday’s post about our evolving perspective on the similarities and differences between PSP and AD?  One reason to be interested in the differences between those two is that a rare disease with limited research funding like PSP could benefit from research on treatments for AD, a very common disease with much more research funding and huge commercial potential.  Besides, we in the PSP community like when drug companies try out their AD drugs on PSP first – because of their common underlying cellular and biochemical similarities. The new paper from WashU has found one more very important similarity.

It’s not only PSP and AD.  The new paper found FAM151B-DT just as relevant to PD and FTDP.  I expect to see research soon on its relevance to others forms of FTD and to ALS, dementia with Lewy bodies, corticobasal degeneration, multiple system atrophy, and many others.  Then we wouldn’t have to worry so much about making an accurate diagnosis early in the disease course– maybe one cure will fit all!

Yes, Congress can accomplish something

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Here’s a great step forward: The Energy and Commerce Committee of the US House of Representatives has just approved the “National Plan to End Parkinson’s Act.”  Thanks in part to advocacy by CurePSP and other organizations devoted to the atypical Parkinsonisms, the bill includes not only PD but also PSP, multiple system atrophy, Lewy body dementia, corticobasal degeneration and Parkinson’s dementia. 

For the remaining required approvals, the bill will now proceed to the full House itself, then the Senate, then the President. (I recited that route for my international readers and for my US readers who doodled through civics class.)  Crucially, the bill was passed with full bipartisan support in the committee, which bodes well for its chances the rest of the way.

Here’s video of the committee’s session.

The bill directs the Department of Health and Human Services to create an advisory commission with representation from all relevant Federal agencies and some advocacy and research organizations as well as patients and caregivers.  Each year, the commission would assess the state of research and clinical care and formulate recommendation on how the various relevant Federal agencies could formulate and coordinate further research plans.  It would also interact with similar organizations internationally. A similar bill for Alzheimer’s disease was enacted in 2011 and has been working successfully by all accounts.

The commission would recommend spending levels for the Federal Government to advance these efforts, but the bill provides no funding for the work of the commission itself.  That would have to be absorbed by the existing budget of the Department of HHS.  (This is standard practice when Congress is interested in a specific medical cause.) 

The bill was first taken up by the committee in March, nine months ago.  One of its major advocates has been Congresswoman Jennifer Wexton of Virginia, who was diagnosed with PSP herself last summer and has been working with CurePSP and others to improve awareness of PSP nationally and to raise funding for research.  Here’s a press release from her office.   The lead sponsor of the bill is Congressman Gus Bilirakis of Florida, who has three close relatives with PD, but 167 other House members signed on as co-sponsors.  The Michael J. Fox Foundation has been working tirelessly for the bill.

I know you’ve been waiting for my editorial commentary.  Here it is:  This is great publicity for PSP, and it sure needs it. 

Congresswoman Wexton is the highest-profile celebrity with PSP since Dudley Moore, the British-American comic actor best known for the movies “10” and “Arthur,” announced his diagnosis of PSP in 1998.  His friends organized a star-studded benefit at Carnegie Hall in New York that raised $50,000 for CurePSP but he declined to become an activist in other ways.  (I was his neurologist, and he told me, “I’ll help out, but don’t want to be the poster child for PSP.”) Linda Ronstadt, the popular singer and Rock and Roll Hall of Fame member, announced in 2019 that her longstanding diagnosis of Parkinson’s had been changed to PSP.  She has not yet supported PSP-related activities of which I’m aware.  A few other less-famous celebrities with PSP have advanced awareness and fundraising, and we’re grateful to them and their families.  But when “progressive supranuclear palsy” is mentioned on the floor of the US House of Representatives and included in press releases, that’s rare and valuable publicity.

Is PSP the route to not just Alzheimer’s but also Parkinson’s?

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We’ve known for many years that Parkinson’s disease, which the textbooks call an α-synucleinopathy, has some aggregated tau as well. It appears that each of the two proteins, once misfolded, not only induces its own normal brethren to misfold, it also induces copies of the other to misfold.
The first demonstration of this synergistic misfolding and resulting aggregation came in a series of three papers between 2002 and 2004 from the lab of John Trojanowski and Virginia Lee at Penn. The first authors were John Duda, Bernard Giasson and Paul Kotzbauer. (Disclaimer: I was one of their co-authors on all three.)

Now, Julia Gerson, a grad student in the lab of Rakez Kayed at the University of Texas Galveston, has presented work at the Society for Neuroscience that harnesses that finding of a PD/tauopathy overlap for therapeutic purposes. (Another disclaimer: Kayed has a related grant from CurePSP, where I chair the grant review.)

Gerson and friends created antibodies directed at oligomeric tau, which is tau in small aggregates of maybe 20 or 30 molecules, which are still small enough to remain in solution in the cytoplasm and therefore invisible to light microscopy, unlike mature neurofibrillary tangles. They didn’t want to target normal, non-aggregated tau for fear of disrupting the normal function of that protein, which is to stabilize microtubules.

They injected those anti-tau antibodies into mice that had a copy of a variant of the human gene encoding α-synuclein. The variation was an G209A mutation, producing an A53T alteration in the resulting protein. This is the mutation that my colleagues and I found in 1997 as the cause of PD in a large Italian-American family with autosomal-dominant PD, a finding that first linked PD with α-synuclein. (That’s Disclaimer #3. You’re starting to see why I’m so interested in this new finding.)

The antibody protected the mice against the loss of dopaminergic neurons that the α-synuclein mutation caused in the untreated mutant mice. Mice that received antibody against normal tau did even more poorly than the controls.

So here’s the take-home: Developing an anti-tau antibody for treatment of PSP may also help Parkinson’s. We already expect that it may help Alzheimer’s because that’s clearly a tau disorder. But now, the synergistic toxicity of tau and α-synuclein could also allow a single anti-tau antibody to protect against both Parkinson’s and dementia with Lewy bodies (which also has aggregation of both proteins).

If I were the drug companies, I’d be sitting up and taking notice. Two companies, Bristol-Myers Squibb and AbbVie (licensing an antibody from C2N) have already started anti-tau antibody trials in people with PSP. Others have anti-tau programs in progress.

This new report, which may extend the utility of those products to Parkinson’s, should give that snowball an extra push.