Protocols by Charles Sieg

The research frontier

Research frontier: Alzheimer's and Parkinson's

The treatments and trials closest to slowing, stopping, or reversing Alzheimer's and Parkinson's, and where each one stands as of November 2026.

Overall evidence Mixed25 sourcesReviewed November 5, 2026

Two antibodies slow early Alzheimer's modestly, stem-cell grafts show early signals in Parkinson's, and several big bets (oral semaglutide, exenatide, a LRRK2 inhibitor) came back negative, so nothing here is a cure.

The short version

  • Nothing I found cures either disease. The nearest things to a disease-modifying treatment are two Alzheimer's antibodies that slow decline by less than a point on an 18-point clinical scale.1,2
  • Phase 3 trials of the antibodies in people without symptoms are under way and have not reported.3,4
  • The most striking early Parkinson's results are cells grafted into the brain, but they come from 12 and 7 people with no control group.5,6
  • Several big bets failed in the last two years: oral semaglutide in Alzheimer's, exenatide in Parkinson's, and a LRRK2 inhibitor, the last according to a company press release.7,8,9
  • I take retatrutide, and none of the trials below tested it.

How I sort a result

"Cure" gets used loosely, so I use four words and say which one a result is:

WordWhat it means here
CureThe disease is gone and stays gone without ongoing treatment. Nothing on this page meets it.
Durable remissionDisease activity stops or reverses for years. Nothing on this page meets it.
SlowingDecline continues, but more slowly than on placebo. The two antibodies are here, and maybe prasinezumab.
Symptom reliefFunction improves without changing the disease course. Deep brain stimulation is here, and the cell transplants might be.

Where each one stands, as of November 2026

TreatmentDiseaseWhat it doesStatus (source)
Lecanemab (Leqembi)Alzheimer'sSlowingFDA traditional approval, July 6, 202310
Donanemab (Kisunla)Alzheimer'sSlowingFDA approval; FDA page current as of July 2, 202411
TrontinemabAlzheimer'sUnknownPhase 3 under way, primary completion estimated February 16, 202812
Antibodies in people without symptomsAlzheimer'sPrevention (unproven)Phase 3 trials running3,4
Oral semaglutideAlzheimer'sNone foundTwo phase 3 trials negative7
LixisenatideParkinson'sPossible slowingOne phase 2 trial positive, 156 people13
ExenatideParkinson'sNone foundPhase 3 negative; the paper is under an expression of concern8,14
Stem-cell dopamine neuronsParkinson'sPossible symptom reliefConditional approval in Japan for raguneprocel (company press release); phase 3 of bemdaneprocel recruiting15,16
PrasinezumabParkinson'sPossible slowingPhase 2b missed its primary endpoint; phase 3 recruiting17,18
BIIB122 (LRRK2 inhibitor)Parkinson'sNone foundPhase 2b negative, per a company press release9
AmbroxolParkinson'sUnknownPhase 3 recruiting, per a registry record last updated May 202519
Adaptive deep brain stimulationParkinson'sSymptom reliefFDA approved February 20, 202520

What the research says

Alzheimer's: the antibodies

Moderate Two antibodies that clear amyloid from the brain slow decline modestly. In CLARITY AD, 1,795 people with early Alzheimer's got lecanemab or placebo for 18 months, and the CDR-SB score (0 to 18, higher is worse) rose by 1.21 versus 1.66 (difference -0.45, 95% CI -0.67 to -0.23).1 In TRAILBLAZER-ALZ 2, 1,736 people got donanemab or placebo for 76 weeks. In the low/medium tau group the iADRS declined 6.02 versus 9.27 points (difference 3.25), and across everyone the CDR-SB difference was -0.7.2 Those are slowing results, not reversal, and they came in people who already had symptoms. Both drugs carry a boxed FDA warning for amyloid-related imaging abnormalities (ARIA), usually temporary brain swelling that can come with small spots of bleeding, and the FDA says ApoE e4 status should be tested before treatment because people with two copies have more ARIA.10,11 ARIA with swelling or fluid occurred in 12.6% of people on lecanemab in its trial, and in 24.0% on donanemab versus 2.1% on placebo in its trial, which also counted 3 treatment-related deaths on donanemab versus 1 on placebo.1,2 I'm reporting what the FDA pages from 2023 and 2024 say, and I did not check for later label changes.

Early Trontinemab is Roche's antibody built to cross the blood-brain barrier more easily. According to the trade outlet NeurologyLive, reporting on Roche's presentation at the 2026 Alzheimer's Association International Conference, the phase 1b/2a BRAINSHUTTLE AD study brought amyloid below the positivity threshold in 91% (49 of 54) at 28 weeks on the higher of two doses, and ARIA-E occurred in fewer than 5% (4 of 149) across both doses.21 That is company-presented and not peer-reviewed, and it measures amyloid, not memory. The phase 3 trial I opened, TRONTIER 1, has 1,101 enrolled, with change in CDR-SB at week 72 as the primary outcome and primary completion estimated for February 16, 2028.12

Early Trials in people without symptoms are the real test of whether clearing amyloid early prevents the disease. AHEAD 3-45 (lecanemab) lists 1,400 estimated participants and an estimated primary completion of December 21, 2028.3 TRAILBLAZER-ALZ 3 (donanemab) lists 2,996 estimated and an estimated primary completion of November 2027.4 Roche presented the design of a third, PrevenTRON, for about 1,600 cognitively unimpaired adults aged 55 to 80 with elevated plasma p-tau217, but the report I read gives no start date.21 None of the three has reported results that I could find.

Alzheimer's: the GLP-1 bet

Strong The idea was that GLP-1 drugs might protect the brain, based on animal studies and on lower dementia risk in people with diabetes or obesity who took them. Two phase 3 trials of oral semaglutide enrolled 3,808 people with early Alzheimer's, and neither met its primary endpoint: in evoke, the CDR-SB worsened by 2.3 points on semaglutide and 2.3 on placebo (difference -0.08, 95% CI -0.35 to 0.20).7 Both were discontinued for negative clinical outcome.7 Two large trials agreeing on a negative result is about as solid as it gets, though they tested an oral pill in people who already had symptoms, not prevention or other GLP-1 drugs.

Parkinson's: GLP-1 drugs

Mixed Lixisenatide, a daily GLP-1 injection, was tested in a phase 2 trial of 156 people diagnosed less than 3 years earlier. The motor score changed by -0.04 points on the drug versus +3.04 on placebo at 12 months (P = 0.007), but nausea hit 46% and vomiting 13%, and the authors call for longer and larger trials.13 Exenatide, a once-weekly GLP-1, was tested in a phase 3 trial of 194 people for 96 weeks and showed no benefit: off-medication motor scores worsened 5.7 points on exenatide and 4.5 on placebo (adjusted effect 0.92, 95% CI -1.56 to 3.39, p=0.47).8 In June 2026 the Lancet's editors attached an expression of concern to that exenatide paper. The record I opened gives no reasons, so I don't know whether the conclusion will change.14 Lixisenatide's result rests on one phase 2 trial, and exenatide is a different drug in the same class, so the two do not settle each other.

Parkinson's: replacing the lost cells

Early Stem-cell transplants are the closest thing to a repair. In the bemdaneprocel phase I trial, 12 people received dopamine neuron precursors made from embryonic stem cells (5 at 0.9 million cells, 7 at 2.7 million), with no adverse events related to the cell product, rising PET uptake at 18 months, no graft-induced dyskinesias, and an average 23-point improvement in the OFF motor score in the high-dose group.5 In a Kyoto trial, 7 people aged 50 to 69 received precursors made from iPS cells. Of the 6 evaluated, 4 improved on the OFF motor score, the average change across all 6 was 9.5 points (20.4%) over 24 months, and there were no serious adverse events.6 Neither trial had a control group, and the bemdaneprocel trial was open-label and gave everyone a year of immune-suppressing drugs, so a placebo effect can't be ruled out.5,6

Sumitomo Pharma and RACTHERA announced that, as of March 6, 2026, Sumitomo Pharma has conditional, time-limited approval in Japan for AMCHEPRY (raguneprocel), the iPS cell product from the Kyoto trial, to improve motor symptoms in people who respond inadequately to existing drugs, including levodopa. The company must run a post-marketing study to obtain full approval.15 That is a company press release about an approval, not a peer-reviewed result, and the approval rests on the small Kyoto trial.15,6 The bemdaneprocel phase 3 trial, exPDite-2, is recruiting, with 102 participants planned, a primary outcome of ON time without troublesome dyskinesia at week 78, and primary completion estimated for October 2028.16 What this could become is symptom relief that lasts. Whether the grafted cells keep working for decades, or change the disease, is unknown.

Parkinson's: slowing the disease

Mixed Prasinezumab is an antibody given by infusion. In PADOVA, 586 people with early Parkinson's got it or placebo for at least 76 weeks, and the primary endpoint, time to confirmed motor progression, was not met (HR 0.84, 95% CI 0.69 to 1.01, p=0.066). The trial was funded by Roche, which is developing the drug.17 The authors describe prespecified exploratory evidence of activity, which is why a phase 3 trial, PARAISO, is recruiting 900 people with a primary completion estimated for June 30, 2029.17,18 I read this as a maybe that will take until 2029 to answer.

Early Some people with Parkinson's carry a pathogenic LRRK2 variant, and a drug that blocks the LRRK2 enzyme was the idea. In a May 21, 2026 press release, Biogen and Denali said the phase 2b LUMA trial of their LRRK2 inhibitor in 648 people with early Parkinson's, with or without the variant, did not slow progression, no secondary endpoint showed a benefit, and they will stop development for idiopathic Parkinson's. Denali is continuing the phase 2a BEACON study in LRRK2 variant carriers, with data expected in the first half of 2027.9 That is a company press release, not yet peer-reviewed, and I did not see the detailed data.

Early Ambroxol, a drug licensed for respiratory conditions in many European countries, is in the UK-only phase 3 ASPro-PD trial run by University College London: 330 people planned, a primary outcome of change in MDS-UPDRS Parts I to III at week 104, and an estimated primary completion of February 2029, per a registry record last updated May 2025.19 It enrolls people with or without a GBA1 gene variant, as long as their status is known before screening.19

Early Finding the right people is part of the problem. In people with REM sleep behavior disorder, the authors estimated that a definitive neuroprotective trial would need 142 to 366 patients per arm, and they say their warning-sign markers can be used to pick patients for such trials.22 The alpha-synuclein spinal fluid test was positive in 44 of 51 people with early warning signs, and its authors likewise suggest it could help build at-risk groups for trials.23

Parkinson's: adaptive deep brain stimulation

Early Deep brain stimulation is an implanted device approved to reduce some symptoms. The FDA approved an optional feature, adaptive DBS, on February 20, 2025, as adjunctive therapy for levodopa-responsive Parkinson's of at least 4 years' duration that medication doesn't adequately control.20 Adaptive stimulation adjusts itself to brain signals, and the version now available follows beta-band signals recorded in the brain.24 The published head-to-head data are tiny: a blinded crossover in 4 men, using a personalized signal that tracks high versus low dopamine states, found adaptive stimulation improved motor symptoms and quality of life over standard stimulation, and a 9-patient double-blind crossover of the beta-band approach found no statistically significant differences.25,24 It is symptom relief by a smarter method, not a treatment that changes the disease.

Cautions

  • Slowing is not stopping. The two approved antibodies slow decline modestly and carry a risk of brain swelling and bleeding.1,2,11
  • Company press releases and trade-press reports are labeled that way here and are not peer-reviewed.21,9,15
  • Registry dates are estimates and move.12,3
  • Nothing on this page is a way to get a drug, and I'm not suggesting anyone take one.
  • I'm not a doctor, and this is what I read, not medical advice.

References

  1. van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in Early Alzheimer's Disease. The New England Journal of Medicine. 2023;388(1):9-21.Randomized trialPubMed 36449413 · DOI

    What it found: CLARITY AD randomized 1,795 people with early Alzheimer's disease (898 lecanemab 10 mg/kg every 2 weeks, 897 placebo) for 18 months. The CDR-SB score worsened by 1.21 on lecanemab and 1.66 on placebo (difference -0.45, 95% CI -0.67 to -0.23, P<0.001), amyloid on PET fell by 59.1 centiloids more, infusion reactions occurred in 26.4%, and ARIA with edema or effusions in 12.6%.

    Limits: An 18-month trial of an intravenous drug that slows decline modestly in people already showing symptoms, so it is not a cure and does not show what happens beyond 18 months.

  2. Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. 2023;330(6):512-527.Randomized trialPubMed 37459141 · DOI

    What it found: TRAILBLAZER-ALZ 2 randomized 1,736 people with early symptomatic Alzheimer's disease (860 donanemab, 876 placebo) for up to 76 weeks. In the low/medium tau group the iADRS declined 6.02 versus 9.27 (difference 3.25, 95% CI 1.88 to 4.62, P<.001); ARIA with edema or effusion occurred in 24.0% on donanemab versus 2.1% on placebo, and there were 3 treatment-related deaths versus 1.

    Limits: A trial of 76 weeks in people who already have symptoms, funded by the maker, showing slowed decline rather than a halt, with a higher rate of brain swelling or bleeding on the drug.

  3. ClinicalTrials.gov (U.S. National Library of Medicine). AHEAD 3-45 Study: A Study to Evaluate Efficacy and Safety of Treatment With Lecanemab in Participants With Preclinical Alzheimer's Disease and Elevated Amyloid and Also in Participants With Early Preclinical Alzheimer's Disease and Intermediate Amyloid. ClinicalTrials.gov, June 4, 2026.Regulatory noticeRead

    What it found: Registry record, last updated June 4, 2026: Eisai's phase 3 AHEAD 3-45 trial of lecanemab in preclinical Alzheimer's disease started July 14, 2020, is active but not recruiting with 1,400 estimated, and lists an estimated primary completion of December 21, 2028; the A45 primary outcome is change in the PACC5 cognitive score at Week 216.

    Limits: A registry listing with no results, and estimated dates move.

  4. ClinicalTrials.gov (U.S. National Library of Medicine). A Donanemab (LY3002813) Study in Participants With Preclinical Alzheimer's Disease (TRAILBLAZER-ALZ 3). ClinicalTrials.gov, January 21, 2026.Regulatory noticeRead

    What it found: Registry record, last updated January 21, 2026: Lilly's phase 3 TRAILBLAZER-ALZ 3 trial of donanemab in preclinical Alzheimer's disease started August 27, 2021, is active but not recruiting with 2,996 estimated, and lists an estimated primary completion of November 2027 for time to clinical progression on the Clinical Dementia Rating.

    Limits: A registry listing with no results, and the record was last updated in January 2026, so a later change would not show here.

  5. Tabar V, Sarva H, Lozano AM, Fasano A, Kalia SK, Yu KKH, et al. Phase I trial of hES cell-derived dopaminergic neurons for Parkinson's disease. Nature. 2025;641(8064):978-983.Cohort studyPubMed 40240592 · DOI

    What it found: Open-label phase I trial of bemdaneprocel, human embryonic stem cell-derived dopamine neuron progenitors grafted into the putamen. Twelve patients were enrolled (5 at a low dose of 0.9 million cells, 7 at a high dose of 2.7 million cells), and all received one year of immunosuppression. No adverse events related to the cell product were reported, PET uptake rose at 18 months, there were no graft-induced dyskinesias, and the OFF motor score improved by an average of 23 points in the high-dose cohort.

    Limits: Twelve people, no control group or placebo, and a one-year course of immunosuppression, so the motor gains could include placebo and surgery effects and are not proof of benefit.

  6. Sawamoto N, Doi D, Nakanishi E, Sawamura M, Kikuchi T, Yamakado H, et al. Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson's disease. Nature. 2025;641(8064):971-977.Cohort studyPubMed 40240591 · DOI

    What it found: Phase I/II trial at Kyoto University Hospital in seven people aged 50 to 69 given iPS-cell-derived dopaminergic progenitors, with six evaluated for efficacy over 24 months. There were no serious adverse events (73 mild to moderate events); four of the six improved on the OFF motor score, the average change across all six was 9.5 points (20.4%), and putamen 18F-DOPA uptake rose 44.7%.

    Limits: Seven people with no control group, so improvements could reflect placebo or surgical effects, and dyskinesia increased while medication doses were kept unchanged.

  7. Cummings JL, Atri A, Sano M, Zetterberg H, Scheltens P, Knop FK, et al. Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials. The Lancet (London, England). 2026;407(10544):2167-2179.Randomized trialPubMed 41865758 · DOI

    What it found: Two phase 3 trials of oral semaglutide in 3,808 people with amyloid-confirmed early Alzheimer's disease (evoke 1,855, evoke+ 1,953) at 566 sites. Neither met its primary endpoint: CDR-SB worsened by 2.3 on semaglutide and 2.3 on placebo in evoke (difference -0.08, 95% CI -0.35 to 0.20, p=0.57), and both trials were discontinued for negative clinical outcome.

    Limits: Funded by Novo Nordisk, and it tested oral semaglutide in people who already had symptoms, so it does not address prevention or other GLP-1 drugs.

  8. Vijiaratnam N, Girges C, Auld G, McComish R, King A, Skene SS, et al. Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial. The Lancet (London, England). 2025;405(10479):627-636.Randomized trialPubMed 39919773 · DOI

    What it found: Phase 3 trial at six UK hospitals randomizing 194 people with Parkinson's disease (97 exenatide 2 mg weekly, 97 placebo) for 96 weeks. Off-medication motor scores worsened by 5.7 points on exenatide and 4.5 on placebo (adjusted effect 0.92, 95% CI -1.56 to 3.39, p=0.47), so there was no evidence of benefit, and serious adverse events occurred in 9 (9%) versus 11 (11%).

    Limits: A negative result in 194 people, and the Lancet later attached an expression of concern to this paper (see vijiaratnam2025eoc) without giving reasons in the record I opened.

  9. Biogen; Denali Therapeutics. Biogen and Denali Therapeutics Provide Update on Phase 2b LUMA Study of BIIB122 (DNL151) in Early-Stage Parkinson's Disease. Company press release (posted on BioSpace), May 21, 2026.ArticleRead

    What it found: Company press release: the phase 2b LUMA trial of the LRRK2 inhibitor BIIB122 in 648 people with early Parkinson's disease (48 to 144 weeks) did not slow progression on the combined MDS-UPDRS Part II and III score, no secondary endpoint showed a benefit, and Biogen and Denali will stop developing it for idiopathic Parkinson's, while Denali continues the phase 2a BEACON study in LRRK2 carriers with data expected in the first half of 2027.

    Limits: A company press release, not peer-reviewed, and I did not open the detailed data.

  10. U.S. Food and Drug Administration. FDA Converts Novel Alzheimer's Disease Treatment to Traditional Approval. FDA News Release, July 6, 2023.Regulatory noticeRead

    What it found: On July 6, 2023 FDA converted Leqembi (lecanemab-irmb) from accelerated to traditional approval for Alzheimer's disease, to be started in mild cognitive impairment or mild dementia, based on the 1,795-patient CLARITY AD trial. The label carries a boxed warning for ARIA, notes higher risk in ApoE e4 homozygotes with testing recommended before treatment, and cautions about anticoagulants.

    Limits: The announcement is from July 2023, so later label changes are not captured here.

  11. U.S. Food and Drug Administration. FDA approves treatment for adults with Alzheimer's disease. U.S. Food and Drug Administration, July 2, 2024.Regulatory noticeRead

    What it found: FDA page (content current as of 07/02/2024) on Kisunla (donanemab-azbt), an IV infusion every four weeks for Alzheimer's disease, started in mild cognitive impairment or mild dementia. In 1,736 randomized patients the iADRS difference was 2.92 and CDR-SB -0.70 at Week 76, and the page carries a boxed warning for ARIA and says ApoE e4 status testing should be performed before treatment.

    Limits: A July 2024 FDA page, so later label updates are not captured, and its date comes from the page's own 'content current as of' line.

  12. ClinicalTrials.gov (U.S. National Library of Medicine). A Study of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease. ClinicalTrials.gov, September 25, 2026.Regulatory noticeRead

    What it found: Registry record, last updated September 25, 2026: a Roche phase 3 trial of trontinemab in early symptomatic Alzheimer's disease, active but not recruiting, started September 17, 2025 with 1,101 enrolled, an estimated primary completion of February 16, 2028, and a primary outcome of change in CDR-SB at Week 72.

    Limits: A registry listing with no results; I opened only this one record, so I cannot describe the companion phase 3 trial from a record I read.

  13. Meissner WG, Remy P, Giordana C, Maltête D, Derkinderen P, Houéto JL, et al. Trial of Lixisenatide in Early Parkinson's Disease. The New England Journal of Medicine. 2024;390(13):1176-1185.Randomized trialPubMed 38598572 · DOI

    What it found: Phase 2 randomized trial of daily lixisenatide versus placebo in 156 people with early Parkinson's disease (78 per group) for 12 months. The motor score changed by -0.04 points on lixisenatide and +3.04 on placebo (difference 3.08, 95% CI 0.86 to 5.30, P = 0.007); after a 2-month washout the scores were 17.7 on lixisenatide and 20.6 on placebo, secondary endpoints did not differ substantially, and nausea occurred in 46% and vomiting in 13%.

    Limits: A phase 2 trial of 12 months in 156 people, with a symptom score that could reflect a drug effect on symptoms rather than slowing of the disease, and the authors call for longer and larger trials.

  14. The Editors of The Lancet. Expression of Concern: Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial. The Lancet (London, England), 2026.ArticlePubMed 42330995 · DOI

    What it found: PubMed record of an Expression of Concern from the editors of The Lancet, published in June 2026 and attached to the February 2025 Lancet trial of exenatide in Parkinson's disease (vijiaratnam2025).

    Limits: The PubMed record contains no notice text, so I do not know the reasons for the concern and cannot say whether the trial's conclusions will change.

  15. Sumitomo Pharma Co., Ltd.; RACTHERA Co., Ltd. Announcement on the Approval for Manufacturing and Marketing Authorization of the Allogeneic iPS Cell-Derived Dopaminergic Neural Progenitor Cell Product "AMCHEPRY" in Japan. Sumitomo Pharma (company press release), March 6, 2026.ArticleRead

    What it found: Company announcement that Sumitomo Pharma and RACTHERA obtained conditional and time-limited approval in Japan on March 6, 2026 for AMCHEPRY (raguneprocel), an allogeneic iPS cell-derived dopaminergic neural progenitor cell product, to improve motor symptoms in people with Parkinson's disease who respond inadequately to existing drugs, with a post-marketing study and surveillance required to obtain full approval.

    Limits: A company press release, not peer-reviewed and not the regulator's own document, and it rests on the small Kyoto trial of seven people.

  16. ClinicalTrials.gov (U.S. National Library of Medicine). A Study to Investigate the Efficacy and Safety of Bemdaneprocel in Adults Who Have Parkinson's Disease. ClinicalTrials.gov, November 2, 2026.Regulatory noticeRead

    What it found: Registry record, last updated November 2, 2026: BlueRock Therapeutics' phase 3 exPDite-2 trial of bemdaneprocel is recruiting, started June 17, 2025, plans 102 participants, has an estimated primary completion of October 2028, and its primary outcome is change in ON-time without troublesome dyskinesia from baseline to Week 78.

    Limits: A registry listing with no results, and estimated dates move.

  17. Nikolcheva T, Pagano G, Anzures-Cabrera J, Trundell D, Kustermann T, Simuni T, et al. Efficacy and safety of intravenous prasinezumab in individuals with early-stage Parkinson's disease on stable symptomatic monotherapy (PADOVA): a phase 2b, multicentre, randomised, double-blind, placebo-controlled study. The Lancet (London, England). 2026;407(10544):2227-2240.Randomized trialPubMed 42208564 · DOI

    What it found: PADOVA randomized 586 people with early Parkinson's disease (293 per group) to prasinezumab 1,500 mg every 4 weeks or placebo for at least 76 weeks. The primary endpoint was not met: time to confirmed motor progression had a hazard ratio of 0.84 (95% CI 0.69 to 1.01, p=0.066), with serious adverse events in 34 of 292 (12%) versus 34 of 290 (12%); the authors describe prespecified exploratory evidence of clinical activity.

    Limits: A missed primary endpoint funded by the maker, so the exploratory signal is a reason for the phase 3 trial and not a result.

  18. ClinicalTrials.gov (U.S. National Library of Medicine). A Study to Evaluate the Efficacy and Safety of Intravenous (IV) Prasinezumab in Participants With Early-Stage Parkinson's Disease. ClinicalTrials.gov, November 5, 2026.Regulatory noticeRead

    What it found: Registry record, last updated November 5, 2026: Roche's phase 3 prasinezumab trial (Prothena Biosciences is a collaborator) is recruiting, started November 24, 2025, plans 900 participants, has an estimated primary completion of June 30, 2029, and its primary outcome is time to confirmed motor progression on MDS-UPDRS Part III up to at least Week 104.

    Limits: A registry listing with no results, and estimated dates move.

  19. ClinicalTrials.gov (U.S. National Library of Medicine). Ambroxol to Slow Progression in Parkinson Disease. ClinicalTrials.gov, May 1, 2025.Regulatory noticeRead

    What it found: Registry record (last update posted May 1, 2025): University College London's UK-only phase 3 ASPro-PD trial of ambroxol, a drug licensed for respiratory conditions in many European countries, is recruiting, started February 25, 2025, plans 330 participants with known GBA1 status (positive or negative), has an estimated primary completion of February 2029, and its primary outcome is change in MDS-UPDRS Parts I to III total score to Week 104.

    Limits: A registry listing with no results, last updated in 2025, and it does not say how many GBA carriers it enrolls.

  20. U.S. Food and Drug Administration. Premarket Approval (PMA) P960009 S478: Activa, Percept and SenSight Deep Brain Stimulation Therapy System. FDA Premarket Approval database, February 20, 2025.Regulatory noticeRead

    What it found: FDA PMA record: supplement S478 to Medtronic's P960009 was received April 17, 2024 and decided February 20, 2025, approving a new optional programming feature called adaptive deep brain stimulation (aDBS) as adjunctive therapy for levodopa-responsive Parkinson's disease.

    Limits: A database entry for a device approval; it gives no trial results.

  21. Meglio M. Roche Unveils PrevenTRON, a Phase 3 Prevention Trial of Trontinemab in Cognitively Unimpaired Individuals at High Risk of Alzheimer Decline. NeurologyLive, July 19, 2026.ArticleRead

    What it found: Trade-press report on Roche's AAIC 2026 presentation of PrevenTRON, a phase 3 trial that will enroll about 1,600 cognitively unimpaired adults aged 55 to 80 with elevated plasma p-tau217, with time to clinical progression as the primary endpoint. It also reports phase 1b/2a BRAINSHUTTLE AD data: at 3.6 mg/kg, amyloid fell below the 24-centiloid threshold in 91% (49/54) after 28 weeks, and ARIA-E occurred in fewer than 5% (4/149) across the 1.8 and 3.6 mg/kg cohorts.

    Limits: A secondary report of company-presented early data and a trial design with no start date, so the numbers are not peer-reviewed efficacy results.

  22. Postuma RB, Iranzo A, Hu M, Högl B, Boeve BF, Manni R, et al. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain. 2019;142(3):744-759.Cohort studyPubMed 30789229 · DOI

    What it found: Multicenter cohort of 1,280 people with polysomnography-confirmed idiopathic REM sleep behavior disorder followed a mean 4.6 years: 6.3% per year converted to an overt neurodegenerative syndrome, and 73.5% had converted by 12 years. An olfactory deficit predicted conversion (hazard ratio 2.62), as did abnormal quantitative motor testing (3.16), and the authors estimate 142 to 366 patients per arm for definitive neuroprotective trials.

    Limits: People with sleep-study-confirmed REM sleep behavior disorder at 24 centers of an international research group, so it does not give the risk for everyone who has a poor sense of smell or occasionally acts out dreams.

  23. Siderowf A, Concha-Marambio L, Lafontant DE, Farris CM, Ma Y, Urenia PA, et al. Assessment of heterogeneity among participants in the Parkinson's Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study. The Lancet. Neurology. 2023;22(5):407-417.Cross-sectional studyPubMed 37059509 · DOI

    What it found: Cross-sectional analysis of 1,123 PPMI participants: the alpha-synuclein seed amplification assay had 87.7% sensitivity for Parkinson's disease (95% CI 84.9 to 90.5) and 96.3% specificity versus healthy controls. It was positive in 44 of 51 prodromal participants with REM sleep behavior disorder or loss of smell, and in 25 of 310 non-manifesting LRRK2 or GBA variant carriers.

    Limits: A research cohort tested at one time point, so it shows the assay can sort groups but not what a positive result means for any one person without symptoms.

  24. Tanimura J, Yako T, Hashimoto T. Clinical Outcomes with Chronic Adaptive Versus Conventional DBS in Parkinson's Disease: A Pilot Randomized Crossover Trial. Movement Disorders Clinical Practice. 2026.Randomized trialPubMed 42765432 · DOI

    What it found: A double-blind randomized crossover pilot of nine people with bilateral subthalamic DBS, one month on conventional and one month on adaptive stimulation. There were no statistically significant differences: ON time favored conventional DBS while troublesome dyskinesia and UPDRS scores favored adaptive DBS, and a Bayesian analysis gave a 29.4% probability of a meaningful conventional advantage for ON time.

    Limits: Nine patients and one month per arm, published online ahead of print in September 2026 without volume or pages in the record.

  25. Oehrn CR, Cernera S, Hammer LH, Shcherbakova M, Yao J, Hahn A, et al. Chronic adaptive deep brain stimulation versus conventional stimulation in Parkinson's disease: a blinded randomized feasibility trial. Nature Medicine. 2024;30(11):3345-3356.Randomized trialPubMed 39160351 · DOI

    What it found: A blinded randomized cross-over pilot trial in four men with Parkinson's disease: adaptive stimulation, which adjusts to brain-signal markers of high versus low dopaminergic states, improved motor symptoms and quality of life compared with clinically optimized standard stimulation.

    Limits: Four patients, so it shows the approach is feasible and not how large or durable the benefit is.