Sepsis causes 48.9 million cases and 11 million deaths worldwide each year, accounting for approximately one in five of all global deaths. ABIONYX Pharma recently announced that a study published in Scientific Reports provides genetic evidence linking apolipoprotein A-I (ApoA-I) levels to sepsis incidence and mortality.
Key Points
- The study, published in Nature Portfolio’s Scientific Reports and titled “Plasma apolipoprotein A-I is a causal protective factor in sepsis,” analyzed UK Biobank data and validated findings across two additional international cohorts. This represents what the company describes as the first genetic proof of a causal relationship between plasma ApoA-I levels and sepsis outcomes.
- Using Mendelian randomization, researchers confirmed the protective effect is causal and independent of other lipid fractions including HDL-C, LDL-C, and triglycerides. Higher apoA-I levels were linked to reduced sepsis incidence, lower mortality in sepsis patients, and decreased circulating bacterial endotoxin levels.
- The proposed mechanism involves apoA-I’s sequestration of bacterial lipopolysaccharide (LPS), a toxin responsible for sepsis manifestations. The study also suggests apoA-I may be effective against Gram-positive sepsis driven by lipoteichoic acid, though specific efficacy data for this mechanism was not provided.
- Findings were replicated across three independent data sets covering both Caucasian and Asian populations. ABIONYX Pharma, which describes itself as dedicated to developing “the world’s only recombinant apoA-I,” described the publication as a milestone in ongoing discussions with what it calls a leading partner in sepsis, though exact partnership details were not disclosed.
The findings suggest patients with naturally higher apoA-I levels may have better outcomes during severe infections, though therapeutic applications remain to be demonstrated.
The Data
- The primary analysis drew from 442,601 UK Biobank participants, including 11,643 sepsis cases.
- Statistical associations showed each standard deviation increase in plasma apoA-I levels corresponded to a 13% reduction in sepsis incidence and a 27% reduction in 28-day mortality rates in patients who developed sepsis.
- Higher apoA-I levels were correlated with reduced circulating endotoxin (LPS) levels.
Industry Context
For decades, the field of sepsis has searched for a causal target. The mechanistic effect of apoA-I and HDL has been well documented over the last 40 years but now, this new genetic validation provides proof that apoA-I is a major factor determining whether patients develop sepsis and whether they survive it.
Dr. Rob Scott, Head of R&D and CMO of ABIONYX Pharma
ABIONYX Pharma characterizes apoA-I as the structural protein that defines high-density lipoprotein (HDL) and positions its recombinant apoA-I technology as a potential therapeutic approach for sepsis. Research over the past four decades has documented apoA-I’s role in modulating inflammatory response and innate immunity, particularly through its interaction with bacterial toxins. The study used Mendelian randomization to confirm the protective effect is causal rather than merely correlational. The announcement noted ongoing discussions with an undisclosed partner in the sepsis field, though no details about the nature, stage, or potential outcomes of these discussions were provided.
