Home › Research › Clinical trials
Multiple-Dose Results from an Ongoing Phase 1 Study of Mivelsiran, an Investigational RNA Interference Therapeutic Targeting Amyloid-Beta Precursor Protein for Alzheimer's Disease
Cohen S, Ducharme S, Brosch JR, et al.. Alzheimer's & Dementia (AAIC 2025 conference abstract), 2025
Topic: Amyloid, tau and blood-test diagnosis
Mivelsiran takes a completely different approach from antibody drugs: it's injected into the spinal fluid and uses RNA interference to tell brain cells to make less of the amyloid precursor protein in the first place, rather than clearing plaques after they form. In this early safety trial, a single dose cut a marker of amyloid production by over 80% within a month, and repeat dosing kept levels suppressed, with only mild-to-moderate side effects reported so far.
Key findings
- Single ascending dose (100mg, n=9) cut CSF sAPPbeta by 84.5% at 1 month, still down 61.1% at 10 months
- Multiple ascending dose (50mg every 6 months, n=10) cut sAPPbeta by up to 83.8% after the second dose
- Administered intrathecally (spinal injection) rather than IV
- Most adverse events were mild-to-moderate; no serious adverse events in the MAD cohort reported to date
- No ARIA data presented in this interim analysis
Why it matters
Mivelsiran takes a completely different approach from antibody drugs: it's injected into the spinal fluid and uses RNA interference to tell brain cells to make less of the amyloid precursor protein in the first place, rather than clearing plaques after they form. In this early safety trial, a single dose cut a marker of amyloid production by over 80% within a month, and repeat dosing kept levels suppressed, with only mild-to-moderate side effects reported so far.
New to this subject? Start with our plain-English guide: Registered clinical trials →
Study details
- Study designphase-1-trial
- Participants19
- Effect sizeSAD 100mg: -84.5% sAPPbeta at month 1, sustained at -61.1% at month 10; MAD 50mg: -63.7% at day 15 post-dose 1, -83.8% at month 1 post-dose 2
- Evidence strengthPreliminary
Limitations
Very small, ongoing Phase 1 safety trial (n=19 total across reported cohorts) reported only as a conference abstract; measures a biomarker (sAPPbeta) rather than any cognitive or clinical outcome, so it says nothing yet about whether this slows disease. Study design is an open-label-style Phase 1 single/multiple ascending dose escalation, a design not captured by the standard study_design categories used here.
How this study scored 16/100
Conference abstract — not peer-reviewed. It scored 26 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, randomised / blinded and indexed in PubMed because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 17 of the 66 points we could judge it on, which is 26 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Alzheimer's & Dementia (AAIC 2025 conference abstract)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | Design recorded as “phase-1-trial”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 2 / 5 | Rated “preliminary” in our summary |
| Peer-review validation | 3 / 10 | Conference abstract — not peer-reviewed. Journal string identifies this as a conference abstract or presentation. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 19 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 0 / 2 | No PubMed ID and no DOI — scores zero (not stated in the record — scored 0) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 17 / 66 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 17 of the 66 points we could judge it on is 26 out of 100. |
| Total | 26 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. This record has no DOI, so the citation leaves it out. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Cohen, S., Ducharme, S., Brosch, JR., et al. (2025). Multiple-Dose Results from an Ongoing Phase 1 Study of Mivelsiran, an Investigational RNA Interference Therapeutic Targeting Amyloid-Beta Precursor Protein for Alzheimer's Disease. Alzheimer's & Dementia (AAIC 2025 conference abstract).
Vancouver
Cohen S, Ducharme S, Brosch JR, et al. Multiple-Dose Results from an Ongoing Phase 1 Study of Mivelsiran, an Investigational RNA Interference Therapeutic Targeting Amyloid-Beta Precursor Protein for Alzheimer's Disease. Alzheimer's & Dementia (AAIC 2025 conference abstract). 2025.
BibTeX
@article{cohen2025-acc6d80e,
author = {Cohen, S. and Ducharme, S. and Brosch, JR. and others},
title = {{Multiple-Dose Results from an Ongoing Phase 1 Study of Mivelsiran, an Investigational RNA Interference Therapeutic Targeting Amyloid-Beta Precursor Protein for Alzheimer's Disease}},
journal = {Alzheimer's \& Dementia (AAIC 2025 conference abstract)},
year = {2025}
}