Welcome news on the PSP Platform Trial (PTP).  As you recall, that’s an NIH-supported organization at about 50 US academic medical centers designed to test three anti-PSP drugs from three different drug companies simultaneously using one placebo group and one administrative apparatus.  The most recent expectation is for a start in the third quarter of 2026.

Other background on the PTP:

• Here’s information from UC San Francisco, one of the headquarters sites
• Here’s CurePSP’s information
• Here’s my most recent post on the PTP

The news is that the PTP has now added the last of the three initial drugs, provisionally called LM11A-31.

It’s an oral drug that interferes with the degenerative scripts in brain cells, potentially giving them a chance to repair themselves.  It accomplishes that by activating a receptor protein on the surface of brain cells called p75^NTR, which modulates the cell’s response to various kinds of insults.   

As you’d guess, this mechanism could apply to many other brain diseases.  In fact, LM11A-31 is being investigated in animal models for Alzheimer’s, Parkinson’s and Huntington’s diseases, HIV dementia, stroke, traumatic brain injury and fetal oxygen deprivation.  However, the lab animal evidence for a strong anti-tauopathy effect seems particularly strong.  I’ll let the mavens explain (nerd alert):

“In AD and tauopathy mouse models, oral administration of LM11A-31 reduced excess activation of enzymes contributing to tau post-translational modifications, accumulation of multiple forms of pathological tau species and tau seeding activity, reduced elevations in multiple microglia and astrocyte markers, and decreased the loss of dendritic spines and synapses while improving performance on hippocampal-dependent memory tasks,”

The paper from which I copied/pasted that was a 6-month, Phase 2 trial of LM11A-31 in 242 people with Alzheimer’s disease.  A third of that group received placebo.  The drug showed acceptable safety and tolerability, with the incidence of side effects of the 200 mg dose about the same as that of the placebo and the 400 mg dose moderately higher.  A secondary aim of the trial was to look for indirect evidence for slowing of progression in various neurodegeneration-related imaging and spinal fluid measures.  Such evidence, promisingly, did occur more frequently in the participants on the active drug than in those on placebo.

But the Phase 2 AD trial’s potentially great news is that the rate of worsening of the cognitive loss itself as measured by each of three standard tests did seem to slow down a bit.  The magnitude of that benefit did not reach statistical significance in the 6 months available, but AD trials designed to detect efficacy (as opposed to safety) generally need a year or two to have much chance of showing a statistically significant effect.

The graphs above show that trial participants with AD who received LM11A-31 progressed a bit more slowly on each of the three cognitive tests than those on placebo.  However, none of the differences reached statistical significance. 

NTB: Neuropsychological Test Battery; ADAS13: 13-item version of the Alzheimer’s Disease Assessment Scale; Mini-Mental Status Exam (from Shanks HRC, et al. Nature Medicine, 2024). https://www.nature.com/articles/s41591-024-02977-w

The diagram below explains the above graph’s components:

• ADAS13 is the cognitive test.
• The upward direction is worse.  Downward is better.
• NS means no statistically significant difference between the active drug and placebo groups.
• The “raw” change (vertical axis label) means that the scores were not adjusted for potentially confounding factors.  Such adjustment of efficacy results is routine in trials designed to assess efficacy, but not in this trial, which was designed to assess safety and tolerability.

The PSP Trial Platform’s study will also be a Phase 2 trial like the AD trial, but it will be scheduled for a full 12 months rather than six.  If it starts in the third quarter of 2026 as planned, the study would be completed in mid-2029.  At that point, the FDA could decide to approve the drug without a large Phase 3 trial if they feel that the results of the Phase 2 are sufficiently favorable and if there’s no other neuroprotective drug for PSP on the market at that point. The other two drugs in the PTP’s inaugural round will be AZP-2006, which enhances the breakdown of abnormal tau by the lysosomes, and AADVac1, an anti-tau active vaccine.

The sponsor of LM11A-31 is a tiny company called PharmatrophiX, Inc., founded by the scientist who discovered the drug, Frank M. Longo, MD PhD, of Stanford University.  https://www.pharmatrophix.com/

Yesterday’s post was about how the 10 most-frequently-visited news items in Parkinson’s News Today (PNT) of 2025 might relate to PSP.  The list appeared here.

I covered items #10 to #6 in my last post.

And now: #5 to #1 . 

#5: FDA clears early trial of stem cell therapy for Parkinson’s

The treatment, called XS-411, is made from stem cells derived from multiple healthy donors and converted into dopamine-producing cells.  Each patient would receive one injection of such cells into each side of the putamen, the brain area where the dopamine synapses are located.  The FDA approved a Phase I trial in April 2025, but now, nine months later, clinicaltrials.gov lists two small studies in China but none in the US.  Most current stem cell trials in neurology derive the cells from the patient’s own bone marrow or skin biopsy, so I really don’t know why the company, XellSmart Bop-Pharmaceutical Company of Suzhow, China, is using cells from people other than the patients themselves.  Maybe they have a new way to suppress the immunologic rejection or maybe production using multiple donors is more easily scalable to serve large numbers of patients.  Could XS-411 work in PSP?  Perhaps it could help the same fraction who respond to levodopa, which is only a minority, and their benefit is usually modest and transient.  The problem is that in PSP, unlike in PD, the cells in the putamen receiving the dopamine-encoded signals are degenerating along with the dopamine-producing cells.  So, we need more research into injecting stem cells producing neuroprotective molecules or non-dopamine neurotransmitters.

#4: Program offers psychedelics as treatment for Parkinson’s

Ibogaine is a psychedelic drug legal only in a few states, and even then only for FDA-approved research use.  Ambio is a company offering the drug to people with a wide variety of conditions on a “research” basis at clinics in Mexico and Malta.  There’s no such listing in clinicaltrials.gov, so I can’t be sure of the protocol except that patients are charged $6,050 for a four-day treatment initiation at one of their clinics and “micro-doses” for the next six months.  Based on the little information available, this fits the profile of many “research trials” of alternative treatments: a hefty fee, minimal pre-treatment evaluation or followup, no control group and no peer-reviewed publication.  In this case, I must also wonder about the risk of habituation to the treatment itself, and where do you suppose you could buy something to satisfy that?  Enough – you now know what I think about this drug for PSP, even if the initial $6,050 and the travel expenses are not an issue for you.  To be sure, some alternative treatments do have legitimate potential, but when there’s a major risk of financial or medical harm (both of which apply here), their use should be confined to formal FDA-approved research protocols.

#3:  Bacteria in digestive tract tied to cognitive decline

Parkinson’s disease is a natural candidate for causation by intestinal bacteria because the first stage of the disease, aggregates of the alpha-synuclein protein in neurons, starts not in the brain, but in the intestines and lungs.  But PSP does appear to start in the brain.  There’s been little research on gut bacteria and PSP, but something important was reported in 2023 from researchers in China and summarized in my 4/2/23 post. That short-term study found that replacing the colonic bacteria produced about a 10 percent benefit in the PSP Rating Scale score.  The trial was too short and small to conclude anything about long-term slowing of progression.  Bottom line: Although PSP does not start in the GI tract as PD does, gut bacteria may play a role and should be studied further for any therapeutic implications. 

#2: Study identifies potential way to treat Parkinson’s constipation

Ghrelin is a string of 28 amino acids with many basic gastrointestinal functions including stimulating appetite at the level of the brain and defecation at the level of the spinal cord.  The article reported by PNT teased out an important detail that could hold implications for treatment of constipation in those with PD.  We don’t know if applies as well to the constipation of PSP, but I can say that some of PSP’s constipation is caused by degeneration of a cluster of cells in the lower spinal cord that are not involved in PD.  One research study, from 2013, did find a role of ghrelin in multiple system atrophy but not in PSP or corticobasal syndrome.  So, those few strands of evidence suggest that people with PSP will have to rely on traditional methods of keeping things moving – exercise, fluids, fiber, a stool softener, and avoidance of drugs that block acetylcholine synapses (“anticholinergics”).  Many drugs in the last category are used for other PSP symptoms such as imbalance, vertigo, urinary incontinence and depression, so getting off those is a good topic for discussion at the neurologist’s office.

#1: Research shows disrupted mitochondrial DNA tied to inflammation

For decades, we’ve known that in both PD and PSP, the cells’ mitochondria malfunction and there’s excessive inflammation in the brain.  But we don’t know which is cause and which is effect, or if they’re both effects of a common cause.  The new study used a novel genetic technique to find evidence that it’s the inflammation causing the mitochondrial loss.  In theory, the same study could be performed in PSP.  A similar result would suggest that to slow PSP progression, targeting excessive inflammation might do better than those targeting mitochondria directly.  Early in my career, I had narrowed my subspecialty choices down to movement disorders and neuroimmunology/multiple sclerosis.  I chose the former because I was flummoxed by the complexity of the immune system.  Little did I know . . .