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38/100

✓ Peer-reviewed alzhub usefulness score 38 out of 100. Drug development

Topic: Gut, metabolism and diet

Plain-language summary

Among the more promising treatments proposed for Alzheimer's disease (AD) and Parkinson's disease (PD) are those reducing brain insulin resistance. The antidiabetics in the class of incretin receptor agonists (IRAs) reduce symptoms and brain pathology in animal models of AD and PD, as well as glucose utilization in AD cases and clinical symptoms in PD cases after their systemic administration. At least 9 different IRAs are showing promise as AD and PD therapeutics, but we still lack quantitative data on their relative ability to cross the blood-brain barrier (BBB) reaching the brain parenchyma. We consequently compared brain uptake pharmacokinetics of intravenous 125 I-labeled IRAs in adult CD-1 mice over the course of 60 min. We tested single IRAs (exendin-4, liraglutide, lixisenatide, and semaglutide), which bind receptors for one incretin (glucagon-like peptide-1 [GLP-1]), and dual IRAs, which bind receptors for two incretins (GLP-1 and glucose-dependent insulinotropic polypeptide [GIP]), including unbranched, acylated, PEGylated, or C-terminally modified forms (Finan/Ma Peptides 17, 18, and 20 and Hölscher peptides DA3-CH and DA-JC4). The non-acylated and non-PEGylated IRAs (exendin-4, lixisenatide, Peptide 17, DA3-CH and DA-JC4) had significant rates of blood-to-brain influx (Ki), but the acylated IRAs (liraglutide, semaglutide, and Peptide 18) did not measurably cross the BBB. The brain influx of the non-acylated, non-PEGylated IRAs were not saturable up to 1 μg of these drugs and was most likely mediated by adsorptive transcytosis across brain endothelial cells, as observed for exendin-4. Of the non-acylated, non-PEGylated IRAs tested, exendin-4 and DA-JC4 were best able to cross the BBB based on their rate of brain influx, percentage reaching the brain that accumulated in brain parenchyma, and percentage of the systemic dose taken up per gram of brain tissue. Exendin-4 and DA-JC4 thus merit special attention as IRAs well-suited to enter the central nervous system (CNS), thus reaching areas pathologic in AD and PD.

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APA 7th

Salameh, T. S., Rhea, E. M., Talbot, K., & Banks, W. A. (2020). Brain uptake pharmacokinetics of incretin receptor agonists showing promise as Alzheimer's and Parkinson's disease therapeutics. Biochemical pharmacology. https://doi.org/10.1016/j.bcp.2020.114187

Vancouver

Salameh TS, Rhea EM, Talbot K, Banks WA. Brain uptake pharmacokinetics of incretin receptor agonists showing promise as Alzheimer's and Parkinson's disease therapeutics. Biochemical pharmacology. 2020. doi:10.1016/j.bcp.2020.114187. PMID: 32755557.

BibTeX

@article{salameh2020-32755557,
  author  = {Salameh, T. S. and Rhea, E. M. and Talbot, K. and Banks, W. A.},
  title   = {{Brain uptake pharmacokinetics of incretin receptor agonists showing promise as Alzheimer's and Parkinson's disease therapeutics}},
  journal = {Biochemical pharmacology},
  year    = {2020},
  doi     = {10.1016/j.bcp.2020.114187},
  pmid    = {32755557},
  url     = {https://doi.org/10.1016/j.bcp.2020.114187}
}

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This page is graded low. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Low means the abstract matched neither pattern. It is the default label, and it does not mean the work is poor; many sound lab and imaging papers land here. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

The non-acylated and non-PEGylated IRAs (exendin-4, lixisenatide, Peptide 17, DA3-CH and DA-JC4) had significant rates of blood-to-brain influx (Ki), but the acylated IRAs (liraglutide, semaglutide, and Peptide 18) did not measurably cross the BBB.

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Study details

Evidence strengthLow

How this study scored 38/100

Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, 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 22 of the 58 points we could judge it on, which is 38 out of 100.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Biochemical pharmacology)
Journal's citation record	— / 4	No journal record from OpenAlex — left out of this score
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	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	2 / 5	2020 — within 10 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	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
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	2 / 2	Indexed in PubMed (PMID 32755557)
Free to read	0 / 2	Behind a paywall — scores zero
Points	22 / 58	Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100.
Total	38 / 100	—

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