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Cobalt-Based Drug Delivery to the Brain using Rapid Short-Pulses of Focused Ultrasound and Microbubbles reduces Aβ aggregation in 5XFAD mice
Morse SV, Rohfleisch L, Geoghegan G, Sujarittam K, Rimer S, Chan TG, Kench T, Pereira MA et al.. Research Square, 2026-07-24
Topic: Disease mechanisms in lab and animal studies
A major obstacle to effective Alzheimer’s disease therapy is the limited ability to deliver therapeutics across the blood-brain barrier. Focused ultrasound with microbubbles can transiently increase BBB permeability, and rapid short-pulse (RaSP) sequences have been shown to improve the safety and efficiency of this approach. Here, we investigated whether repeated RaSP-ultrasound treatments could deliver the cobalt-based compound CoLAm2, an inhibitor of amyloid-β (Aβ) oligomerization, to the brains of 5xFAD mice. Five-month-old mice received three weekly treatments consisting of intravenous CoLAm2 (5 mg/kg) and targeted BBB opening in the left hippocampus using RaSP ultrasound sequences. Immunohistochemistry demonstrated a 60.5% reduction in Aβ plaque area in mice receiving combined focused ultrasound and CoLAm2 compared with ultrasound-only, drug-only, and untreated controls. Ultrasound-only treatment also reduced aggregated Aβ by 35.6%, as assessed by Thioflavin S staining. Open field and novel object recognition tests detected no adverse effects on locomotor activity, anxiety-like behaviour, or cognition following repeated treatments. These findings demonstrate that repeated RaSP-ultrasound enables safe delivery of a small-molecule therapeutic across the BBB and enhances its anti-amyloid effects in a mouse model of Alzheimer’s disease, supporting further investigation of this approach for neurological disorders.
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APA 7th
Morse, S. V., Rohfleisch, L., Geoghegan, G., Sujarittam, K., Rimer, S., Chan, T. G., et al. (2026). Cobalt-Based Drug Delivery to the Brain using Rapid Short-Pulses of Focused Ultrasound and Microbubbles reduces Aβ aggregation in 5XFAD mice. Research Square. https://doi.org/10.21203/rs.3.rs-10332117/v1
Vancouver
Morse SV, Rohfleisch L, Geoghegan G, Sujarittam K, Rimer S, Chan TG, et al. Cobalt-Based Drug Delivery to the Brain using Rapid Short-Pulses of Focused Ultrasound and Microbubbles reduces Aβ aggregation in 5XFAD mice. Research Square. 2026. doi:10.21203/rs.3.rs-10332117/v1.
BibTeX
@article{morse2026-aa1d8498,
author = {Morse, S. V. and Rohfleisch, L. and Geoghegan, G. and Sujarittam, K. and Rimer, S. and Chan, T. G. and Kench, T. and Pereira, M. A. and others},
title = {{Cobalt-Based Drug Delivery to the Brain using Rapid Short-Pulses of Focused Ultrasound and Microbubbles reduces Aβ aggregation in 5XFAD mice}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10332117/v1},
url = {https://doi.org/10.21203/rs.3.rs-10332117/v1}
}
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Key findings
- Immunohistochemistry demonstrated a 60.5% reduction in Aβ plaque area in mice receiving combined focused ultrasound and CoLAm2 compared with ultrasound-only, drug-only, and untreated controls.
- These findings demonstrate that repeated RaSP-ultrasound enables safe delivery of a small-molecule therapeutic across the BBB and enhances its anti-amyloid effects in a mouse model of Alzheimer’s disease, supporting further investigation of this approach for neurological disorders.
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Study details
- Effect size60.5%; 35.6%
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 27 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size and randomized / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 17 of the 62 points we could judge it on, which is 27 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “5xfad”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization 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 | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 17 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 17 of the 62 points we could judge it on is 27 out of 100. |
| Total | 27 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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