THR-184

Summary

THR-184 is an investigational synthetic peptide that mimics bone morphogenetic protein‑7 (BMP‑7) activity and antagonises transforming growth factor‑β (TGF‑β) signaling. It is being studied primarily as a renal‑protective agent to prevent or lessen acute kidney injury (AKI), especially in patients undergoing high‑risk cardiovascular surgery.

Mechanism of Action

THR-184 binds to BMP receptors, promoting phosphorylation of Smad‑1/5/8 and activating downstream BMP‑7 pathways that support cell survival and repair. Simultaneously it blocks TGF‑β signaling, reducing pro‑fibrotic and pro‑inflammatory transcriptional programs. In renal tubular cells this dual action dampens apoptosis, inflammation, fibrosis and the epithelial‑to‑mesenchymal transition that contribute to AKI.

What the Research Shows

Pre‑clinical work demonstrated that THR‑184 binds BMP receptors, triggers Smad‑1/5/8 phosphorylation, and attenuates ischemia‑reperfusion‑induced AKI in rat models. The peptide progressed through phase I safety studies and entered phase II trials in adults at high risk for AKI after cardiac surgery. A randomized, double‑blind, placebo‑controlled trial of 452 patients found no significant reduction in AKI incidence, severity, or duration, and composite outcomes of death, dialysis, or persistent renal dysfunction were unchanged. Review articles cite THR‑184 as a promising repair‑oriented agent, but note the lack of efficacy in the completed cardiac‑surgery trial.

Reported Benefits

Animal studies suggest THR‑184 can limit renal inflammation, cell death, fibrosis, and EMT, thereby preserving kidney function after acute injury. Early human trials confirmed that intravenous administration is well tolerated, with safety profiles comparable to placebo. The peptide’s small size may overcome manufacturing and immunogenicity challenges associated with full‑length growth factors.

Limitations of the Evidence

The sole large phase II cardiac‑surgery trial did not demonstrate clinical benefit, raising questions about dose, timing, or patient selection. Evidence is limited to this single indication; no data exist for sepsis‑related, transplant‑related, or other AKI contexts. Long‑term outcomes and effects on chronic kidney disease progression remain unstudied, and the overall clinical development program appears to have stalled.

Safety Considerations

In the peri‑operative cardiac‑surgery study, adverse event rates, including hypotension, infection, and allergic reactions, were similar between THR‑184 and placebo groups. No dose‑limiting toxicities were reported, and the peptide was generally well tolerated. However, the safety data are confined to short‑term exposure; longer‑term safety has not been established.

How It Is Administered

THR‑184 is delivered as an intravenous infusion, typically administered peri‑operatively around the time of cardiac surgery. The formulation is a sterile peptide solution intended for infusion over a defined period; specific dosing regimens have varied across trial cohorts.

Routes of Administration

Goals & Uses

• Dry eye diseaseOphthalmologyModerate
• Corneal epithelial wound healingWound HealingModerate
• Reduction of renal tubular apoptosisCell SurvivalLow
• Prevention of acute kidney injuryRenoprotectionModerate
• Attenuation of ischemia-reperfusion injuryCytoprotectionModerate
• Reduction of renal fibrosisAntifibroticLow

Contraindications

• Hypersensitivity to THR-184 or excipientsAllergic/ImmunologicHigh
• Known hypersensitivity to peptide componentsAllergyHigh
• Active malignancy with BMP pathway involvementOncologyModerate

Adverse Effects

• HeadacheNeurologicUncommonPain in the head or upper neck
• Electrolyte disturbancesMetabolicUnknown
• HypotensionCardiovascularUnknownLow blood pressure
• NauseaGastrointestinalUnknownFeeling of sickness or urge to vomit
• Injection site / infusion reactionsLocal/SystemicUnknown
• Transient ocular irritationLocalCommon

Drug Interactions

• Topical corticosteroidsLow
• TGF-β inhibitorsLow
• DiureticsLowMay worsen dehydration or electrolyte imbalance

Population Constraints

• Patients with end-stage renal diseaseRenal ImpairmentRelative
• Pediatric patientsAgeRelative
• Pediatric patients (<12 y)AgeRelative
• Pregnant or lactating womenReproductiveRelative
• Pregnant womenReproductiveRelative
• Patients with known BMP pathway malignanciesOncologyRelative

Regulatory Status

• European UnionInvestigationalUnder evaluation; no marketing authorization.
• United StatesInvestigationalPhase II clinical trials for dry eye; not FDA‑approved.
• United KingdomInvestigationalNo MHRA approval; participated in multi-center trials

Not approved by FDA, EMA, or other regulatory agencies. Investigated under IND/clinical trial frameworks. Development was primarily led by Thrasos Therapeutics (Canada). Phase 2 trials were conducted; no Phase 3 program has been publicly announced.

Evidence & Sources

• Acute kidney injury: emerging pharmacotherapies in current clinical trials
  Journal ArticleModerateBenoit SW, Devarajan P2018-01-01T00:00:00.000000Z
• Perioperative THR-184 and AKI after Cardiac Surgery
  Journal ArticleModerateHimmelfarb J, et al.2018-01-01T00:00:00.000000Z
• A Process for the Design and Development of Novel Bone Morphogenetic Protein-7 (BMP-7) Mimetics With an Example: THR-184
  Journal ArticleLowCarlson WD, et al.2022-01-01T00:00:00.000000Z
• Recent early clinical drug development for acute kidney injury
  Journal ArticleModerateGallagher KM, et al.2017-01-01T00:00:00.000000Z
• Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop is required for interleukin (IL)-1-mediated optimal NFkappaB and AP-1 activation as well as IL-6 gene expression
  Journal ArticleLowYu Y, et al.2008-01-01T00:00:00.000000Z
• Challenges and advances in the treatment of AKI
  Journal ArticleModerateKaushal GP, Shah SV2014-01-01T00:00:00.000000Z

Frequently Asked Questions