Progressive supranuclear palsy: 2026 so far

Biomarker target engagement outpaced measurable short-term clinical change.

In January 2026 to September 2026, controlled PSP treatment studies more often showed changes in lab biomarkers than changes in day-to-day disability measures. In a small phase 1b trial (an early study mainly checking safety and dosing), bepranemab led to about an 80% reduction in a targeted CSF free tau measure (a tau protein measure in spinal fluid) and was described as generally well tolerated. The study was not sized to show firm clinical effects. In a small phase 2a trial (a mid-stage trial testing whether a treatment works and is safe), TPN-101 was described as generally well tolerated and lowered CSF neurofilament light (a nerve-injury protein measured in spinal fluid) in a dose-related way. However, PSP Rating Scale disability scores did not differ from placebo over 24 weeks. This means early PSP trial headlines can reflect biological target engagement without showing a near-term functional benefit within the same study timeframe.

Research covered in: March 2026, August 2026

Sex-stratified analyses raised questions about who benefits from treatment.

In January 2026 to September 2026, one year-long analysis that looked at results separately by sex reported that davunetide's effects appeared clearer in women than in men with PSP. The analysis found a statistically significant treatment effect favoring women on the PSPRS-10 over 52 weeks. It also reported improvements for women in several cognitive areas, while the same pattern was not reported for men in the summary. The same work reported that links between a CSF tau ratio (p-tau/total tau) and functional outcomes went in opposite directions depending on sex. This adds uncertainty about whether some PSP treatments (and how biomarkers are interpreted) could differ in meaningful ways between women and men, and it points to the need for confirmation in prospectively designed studies.

Research covered in: July 2026

Swallowing decline was tracked, while PEG outcomes stayed observational.

Between January and September, several studies focused on swallowing decline and nutrition decisions as day-to-day PSP care issues. A longitudinal study in 61 people found dysphagia (trouble swallowing) worsened over time. This included changes in swallowing scores and tongue-pressure measures. The changes tracked with changes in a PSP severity scale, and one swallowing score worsened faster in people with a speech-language-predominant presentation. Separately, a retrospective cohort in atypical parkinsonism (including PSP) reported that PEG feeding-tube placement (a stomach feeding tube placed through the skin) was linked to longer survival when counted from dysphagia onset. It was not linked to fewer aspiration pneumonia hospital admissions. Together, these findings support that swallowing can measurably worsen over time, and that PEG may relate to survival in observational data without showing fewer aspiration-pneumonia admissions in the same dataset.

Research covered in: January 2026, March 2026, May 2026

Fall-risk measurement and short-term balance rehab signals became clearer.

In January 2026 to September 2026, studies linked measurable balance problems to near-term falls and described early rehabilitation results. In a prospective cohort of 54 people with PSP, lower Mini-BESTest scores at discharge predicted more frequent falls over the next month. This supports structured balance testing as a practical near-term risk signal. A physiotherapy report in one person with PSP described potential functional improvement, while a 7-person mixed extrapyramidal case series reported short-term balance gains with supervised immersive virtual reality training added to usual inpatient therapy. Walking speed changes were not statistically significant. Mild short-lived symptoms (fatigue, eyestrain, dizziness) were noted in the VR series. Overall, fall risk and balance change can be measured in ways that relate to near-term outcomes, while rehab evidence remains small and short-term.

Research covered in: January 2026, June 2026

Clinic cohorts highlighted treatable symptom burdens and caregiver impact.

By September, observational clinic cohorts highlighted symptoms that can strongly affect daily life and caregiver strain. In a prospective clinic cohort of 88 people with PSP, dystonia (sustained muscle contractions causing twisting or abnormal postures) was reported in 64.8%, with subtype-related patterns. Among 19 treated with botulinum toxin injections, 12 had marked improvement and 7 had partial improvement, with no worsening reported. Another cohort study reported groaning in 20.0% of people with PSP and found it was linked to worse disease severity, lower daily function, and higher caregiver burden. These results suggest some non-core motor symptoms (like dystonia) were common and had reported improvement with targeted treatment in a treated subgroup, while other symptoms (like groaning) were associated with higher disability and caregiver burden.

Research covered in: September 2026