Home › Research › Inflammation and the immune system
CHF5074 reduces biomarkers of neuroinflammation in patients with mild cognitive impairment: a 12-week, double-blind, placebo-controlled study
Ross J, Sharma S, Winston J, Nunez M, Bottini G, Franceschi M, Scarpini E, Frigerio E et al.. Current Alzheimer research, 2013-09-01
Topic: Brain proteins, microglia and lab models
As neuroinflammation is an early event in the pathogenesis of Alzheimer' s disease, new selective antiinflammatory drugs could lead to promising preventive strategies. We evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of CHF5074, a new microglial modulator, in a 12-week, double-blind, placebo-controlled, parallel groups, ascending dose study involving 96 MCI patients. Subjects were allocated into three successive study cohorts to receive ascending, titrated doses of CHF5074 (200, 400 or 600 mg/day) or placebo. Vital signs, cardiac safety, neuropsychological performance and safety clinical laboratory parameters were assessed on all subjects. Plasma samples were collected throughout the study for measuring drug concentrations, soluble CD40 ligand (sCD40L) and TNF-α. At the end of treatment, cerebrospinal fluid (CSF) samples were optionally collected after the last dose to measure drug levels, β- amyloid1-42 (Aβ42), tau, phospho-tau181, sCD40L and TNF-α. Ten patients did not complete the study: one in the placebo group (consent withdrawn), two in the 200-mg/day treatment group (consent withdrawn and unable to comply) and seven in the 400-mg/day treatment group (five AEs, one consent withdrawn and one unable to comply). The most frequent treatment-emergent adverse events were diarrhea, dizziness and back pain. There were no clinically significant treatmentrelated clinical laboratory, vital sign or ECG abnormalities. CHF5074 total body clearance depended by gender, age and glomerular filtration rate. CHF5074 CSF concentrations increased in a dose-dependent manner. At the end of treatment, mean sCD40L and TNF-α levels in CSF were found to be inversely related to the CHF5074 dose (p=0.037 and p=0.001, respectively). Plasma levels of sCD40L in the 600-mg/day group were significantly lower than those measured in the placebo group (p=0.010). No significant differences between treatment groups were found in neuropsychological tests but a positive dose-response trend was found on executive function in APOE4 carriers. This study shows that CHF5074 is well tolerated in MCI patients after a 12-week titrated treatment up to 600 mg/day and dose-dependently affects central nervous system biomarkers of neuroinflammation.
Key findings
- There were no clinically significant treatmentrelated clinical laboratory, vital sign or ECG abnormalities.
- Plasma levels of sCD40L in the 600-mg/day group were significantly lower than those measured in the placebo group (p=0.010).
- No significant differences between treatment groups were found in neuropsychological tests but a positive dose-response trend was found on executive function in APOE4 carriers.
Why it matters
In a 12-week placebo-controlled trial in 96 people with mild cognitive impairment, CHF5074, a drug designed to modulate microglia, was well tolerated at doses up to 600 mg/day. Higher doses were linked to lower levels of the inflammation markers sCD40L and TNF-α in cerebrospinal fluid, but thinking tests showed no significant differences between groups, apart from a positive trend in executive function in APOE4 carriers. As an early safety study, it supports further testing rather than showing a clinical benefit.
Study details
- Study designrandomized controlled trial
- Evidence strengthLow
How this study scored 53/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 50 of the 94 points we could judge it on, which is 53 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Current Alzheimer research) |
| Journal's citation record | 1 / 4 | Current Alzheimer Research: journal h-index 119 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — within 20 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 | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 4 / 7 | Cited 79 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.3 citations a year over 15 year(s) since 2013 |
| 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 | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Bruno Pietro Imbimbo: h-index 64 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Memory Enhancement Center of America: institution h-index 8 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23968157) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 50 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 50 of the 94 points we could judge it on is 53 out of 100. |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. 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
Ross, J., Sharma, S., Winston, J., Nunez, M., Bottini, G., Franceschi, M., et al. (2013). CHF5074 reduces biomarkers of neuroinflammation in patients with mild cognitive impairment: a 12-week, double-blind, placebo-controlled study. Current Alzheimer research. https://doi.org/10.2174/13892037113149990144
Vancouver
Ross J, Sharma S, Winston J, Nunez M, Bottini G, Franceschi M, et al. CHF5074 reduces biomarkers of neuroinflammation in patients with mild cognitive impairment: a 12-week, double-blind, placebo-controlled study. Current Alzheimer research. 2013. doi:10.2174/13892037113149990144. PMID: 23968157.
BibTeX
@article{ross2013-23968157,
author = {Ross, J. and Sharma, S. and Winston, J. and Nunez, M. and Bottini, G. and Franceschi, M. and Scarpini, E. and Frigerio, E. and others},
title = {{CHF5074 reduces biomarkers of neuroinflammation in patients with mild cognitive impairment: a 12-week, double-blind, placebo-controlled study}},
journal = {Current Alzheimer research},
year = {2013},
doi = {10.2174/13892037113149990144},
pmid = {23968157},
url = {https://doi.org/10.2174/13892037113149990144}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
3 studies in the alzhub library list this one in their references.
Related studies in Inflammation and the immune system
Also tagged “mice”
1,150 studies in the library carry the topic tag “mice”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.