Recombinant human plasma gelsolin
Also known as: BioAegis rhu-pGSN, GELSOL, pGSN, Plasma gelsolin replacement therapy, recombinant plasma gelsolin, rhu-pGSN
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Summary
Recombinant human plasma gelsolin (rhu‑pGSN) is an 83 kDa actin‑binding protein produced by recombinant technology and administered intravenously. It is being explored as an investigational immunomodulatory therapy for conditions marked by excessive inflammation, such as severe COVID‑19 pneumonia, community‑acquired pneumonia, and decompression‑related neuroinflammation.
Mechanism of Action
Plasma gelsolin binds and severs filamentous actin, limiting actin‑induced microvascular injury. In cell and animal models it dampens pro‑inflammatory signaling through inhibition of PI3K/AKT, MAPK, and NF‑κB pathways, reduces cytokine release (IL‑6, IL‑8, TNF‑α), and promotes expression of tight‑junction proteins (ZO‑1, occludin, claudin‑5). These actions collectively protect endothelial barriers and attenuate neuroinflammatory cascades.
What the Research Shows
In vitro studies showed rhu‑pGSN restored blood‑brain barrier integrity after exposure to the SARS‑CoV‑2 spike protein, normalising electrical resistance and tight‑junction protein levels while suppressing inflammatory signaling. A murine decompression‑sickness model demonstrated that delayed rhu‑pGSN infusion lysed inflammatory microparticles, reduced cytokines, and rescued hippocampal neurogenesis and cognitive function. A blinded, randomized adjunctive trial in severe COVID‑19 pneumonia (61 patients) found no statistically significant clinical benefit over placebo, though serious adverse events were numerically lower in the rhu‑pGSN arm. A dose‑escalation safety study in non‑ICU community‑acquired pneumonia patients reported mild adverse events and a half‑life >17 h, supporting tolerability. Production methods enabling gram‑scale, functional protein have also been described.
Reported Benefits
Preclinical data indicate rhu‑pGSN can protect endothelial barriers, lower cytokine production, and reverse neuroinflammatory damage in animal models. Early human trials suggest the protein is well tolerated, with no drug‑related serious adverse events and a potential trend toward fewer severe complications in COVID‑19 and pneumonia cohorts, although definitive efficacy has not been demonstrated.
Limitations of the Evidence
Clinical evidence is limited to small, early‑phase studies; the COVID‑19 trial did not achieve a statistically significant improvement in primary outcomes. Sample sizes are modest, and most data derive from in vitro or murine models, which may not translate to human disease. The optimal dosing regimen, timing, and patient populations remain undefined, and larger controlled trials are needed.
Safety Considerations
Across studies, rhu‑pGSN was generally well tolerated. Reported mild adverse events included nausea and transient blood‑pressure elevation. No drug‑related serious adverse events occurred in the pneumonia dose‑escalation study, and the COVID‑19 trial identified no new safety signals. One death in the COVID‑19 cohort was unrelated to the study drug. The protein’s half‑life exceeds 17 hours, allowing sustained supraphysiologic plasma levels with repeat dosing.
How It Is Administered
rhu‑pGSN is delivered as an intravenous infusion. Clinical investigations have employed single or three‑day dosing regimens ranging from 6 mg/kg to 24 mg/kg body weight. The formulation is a sterile recombinant protein solution suitable for infusion over a short period.
Routes of Administration
Goals & Uses
- Sepsis treatmentInfectious DiseaseModerate
- Acute respiratory distress syndromePulmonaryModerate
- Scavenging extracellular actin in critical illnessPathophysiology CorrectionModerate
- Acute kidney injury prevention in critical illnessNephrologyLow
- Attenuation of ARDS / acute lung injuryCritical Care / PulmonologyModerate
- Reduction of systemic inflammation in sepsisAnti Inflammatory / Critical CareLow
- COVID-19 severe disease managementInfectious Disease / Critical CareLow
Contraindications
- Known hypersensitivity to gelsolin productAllergyHigh
- Severe uncontrolled coagulopathyHematologyModerate
- Known hypersensitivity to recombinant human proteins or CHO-derived productsAllergy / ImmunologyHigh
Adverse Effects
- Headache / myalgiaGeneralUncommon
- Anti-drug antibody formationImmunologicalUnknown
- Infusion-related reactionsHypersensitivityUncommon
- Transient hypotensionCardiovascularRare
Drug Interactions
- Other recombinant protein biologicsLow
- Anticoagulants (e.g., heparin, warfarin)Low
- Concomitant immunosuppressantsModerate
Population Constraints
- Severe renal impairmentOrgan ImpairmentRelative
- Pediatric patientsAgeRelative
- Pregnant or lactating womenReproductiveRelative
- Patients with pre-existing autoimmune conditionsImmunologicRelative
- Pregnant womenReproductiveRelative
- Renal or hepatic impairmentOrgan DysfunctionRelative
Regulatory Status
- European UnionInvestigationalUnder EMA scientific advice
- United StatesInvestigationalPhase II/III clinical trials for sepsis
- United KingdomInvestigationalNo MHRA approval. Clinical trial access only.
No FDA, EMA, or MHRA marketing approval as of 2024. Designated as an orphan drug candidate for certain indications in exploratory trials. Developed primarily by BioAegis Therapeutics. Multiple Phase I/II trials conducted.
Evidence & Sources
- Journal ArticleLowSuprewicz Ł, et al.2022-01-01T00:00:00.000000Z
- Journal ArticleLowBhat AR, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleLowDiNubile MJ, et al.2022-01-01T00:00:00.000000Z
- Journal ArticleModerateKontogiannis DS, et al.2025-01-01T00:00:00.000000Z
- Journal ArticleLowKim YS, et al.2025-01-01T00:00:00.000000Z
- Journal ArticleModerateTannous A, et al.2020-01-01T00:00:00.000000Z
Frequently Asked Questions
What condition is rhu‑pGSN being tested for?
It is under investigation as an adjunctive therapy for inflammatory disorders such as severe COVID‑19 pneumonia, community‑acquired pneumonia, and decompression‑related neuroinflammation, but it is not yet approved for any indication.
How does rhu‑pGSN differ from standard anti‑inflammatory drugs?
Unlike conventional drugs that target specific cytokines or pathways, rhu‑pGSN acts upstream by binding actin, modulating multiple signaling cascades, and enhancing endothelial barrier integrity, offering a broader immunomodulatory effect.
Is rhu‑pGSN safe to use?
Early-phase trials report mild adverse events and no drug‑related serious adverse events, suggesting a favorable safety profile, though larger studies are required to confirm safety across broader patient groups.
How is the drug administered?
It is given intravenously, typically as a short infusion. Dosing in studies has ranged from 6 mg/kg to 24 mg/kg, administered once or over three consecutive days.
When might rhu‑pGSN become an approved therapy?
Approval depends on the outcomes of larger, controlled clinical trials that demonstrate clear efficacy and safety; at present it remains investigational.
What is Recombinant human plasma gelsolin?
Recombinant human plasma gelsolin (rhu‑pGSN) is an 83 kDa actin‑binding protein produced by recombinant technology and administered intravenously. It is being explored as an investigational immunomodulatory therapy for conditions marked by excessive inflammation, such as severe COVID‑19 pneumonia, community‑acquired pneumonia, and decompression‑related neuroinflammation.
What is Recombinant human plasma gelsolin used for?
Recombinant human plasma gelsolin is educationally associated with: Sepsis treatment, Acute respiratory distress syndrome, Scavenging extracellular actin in critical illness, Acute kidney injury prevention in critical illness, Attenuation of ARDS / acute lung injury, Reduction of systemic inflammation in sepsis, COVID-19 severe disease management. Educational only — not medical advice.
How is Recombinant human plasma gelsolin administered?
Recorded routes of administration: Intravenous.
What are the potential side effects of Recombinant human plasma gelsolin?
Reported adverse effects include: Headache / myalgia, Anti-drug antibody formation, Infusion-related reactions, Transient hypotension. This list is not exhaustive — consult a qualified clinician.
Who should avoid Recombinant human plasma gelsolin?
Recorded contraindications: Known hypersensitivity to gelsolin product, Severe uncontrolled coagulopathy, Known hypersensitivity to recombinant human proteins or CHO-derived products. Consult a qualified clinician before use.