Evidence map›Paper›PMID 38974609›Full record

ArticleJIMD reports2024

Elevated homocysteine is negatively correlated with plasma cystathionine β-synthase activity in givosiran-treated patients.

Mark A Keibler, Gautham V Sridharan, Marianne T Sweetser, Simina Ticau

Abstract read
In one paragraph

Article in JIMD reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Mark A KeiblerResearch Alnylam Pharmaceuticals Cambridge Massachusetts USA.ORCID https://orcid.org/0000-0002-5410-6543
Gautham V SridharanResearch Alnylam Pharmaceuticals Cambridge Massachusetts USA.
Marianne T SweetserClinical Research Alnylam Pharmaceuticals Cambridge Massachusetts USA.
Simina TicauResearch Alnylam Pharmaceuticals Cambridge Massachusetts USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Givosiran is a subcutaneously administered, liver-targeted RNA interference (RNAi) therapeutic that has been approved for treating acute hepatic porphyria (AHP). Elevation in plasma homocysteine (hyperhomocysteinemia) has been reported in AHP patients, and treatment with givosiran has been reported to further increase homocysteine levels in some patients. The mechanism of homocysteine elevation during givosiran treatment is unknown, but has been hypothesized to be mediated by a reduction in activity of cystathionine β-synthase (CBS), which uses homocysteine as a substrate. A liquid chromatography-tandem mass spectrometry-based assay was adapted to measure circulating CBS activity. Using plasma collected from the Phase III ENVISION study, CBS activity was measured to directly evaluate whether it is associated with elevated homocysteine levels in givosiran-treated patients. CBS activity was reduced following givosiran treatment and both homocysteine and methionine levels were inversely correlated with CBS activity. Following administration of a supplement containing vitamin B

Indexed as

Acute hepatic porphyria (AHP)cystathionine β‐synthase (CBS)givosiranhomocysteinehyperhomocysteinemialiquid chromatography‐mass spectrometry (LC–MS)noninvasive diagnostics

Identifiers

PMID38974609
PMCPMC11224493

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.