PCSK1 (Proprotein Convertase Subtilisin/Kexin Type 1)

P3, N=296, Active, not recruiting, Rhythm Pharmaceuticals, Inc. | Trial completion date: Dec 2025 --> Dec 2026

P=N/A, N=1100, Completed, Hospices Civils de Lyon | Not yet recruiting --> Completed | Trial completion date: Apr 2026 --> Jun 2025 | Trial primary completion date: Apr 2026 --> Jun 2025

Therapy was temporarily discontinued. To our knowledge, this is the first reported pediatric case with LEPR-related monogenic obesity developing dysplastic nevi during setmelanotide use.

Our study identifies a metastasis-enriched, terminally differentiated PCSK1+ subpopulation and elucidates its potential regulatory and microenvironmental characteristics. These findings enhance our understanding of the cellular states linked to the progression of PNETs and lay the groundwork for subsequent mechanistic investigations.

RNA-sequencing results proved the PCSK1, PCSK2, and PCSK9 downregulation in OLE-treated recurrent tumors versus vehicle control. Oleuropein is a novel lead useful for the control of mCRPC progression and the prevention of its recurrence via targeting PCSK9 expression and PPI with LDLR.

Inactive B. thetaiotaomicron and B. fragilis increased GCG mRNA levels and GLP-1 concentration, with inactive B. fragilis also elevating GLP-2 protein levels.This study suggests that B. thetaiotaomicron and its derivatives, particularly CFS and OMVs, have potential as next-generation probiotics, postbiotics, and paraprobiotics for modulating satiety hormones and managing obesity. Further research is warranted to explore their mechanisms and therapeutic applications in vivo.

P3, N=400, Active, not recruiting, Rhythm Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting

P=N/A, N=240, Recruiting, IRCCS Azienda Ospedaliero-Universitaria di Bologna

P3, N=400, Recruiting, Rhythm Pharmaceuticals, Inc. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

PCSK1N is higher in SCA compared with FCA, and associated with corticotroph cell markers and tumor size. PCSK1N is likely to be part of the adaptive response to ER stress, potentially conferring a survival advantage to the corticotroph tumor cell in conjunction with other proteins.

Further analysis found that PMEL expression negatively correlated with the reduction rate of TSC-RAMLs after mTORC1 inhibitor treatment (r = -0.50, p = 0.0022), both after 3 months (r = -0.47, p = 0.048) and 6 months of treatment (r = -0.52, p = 0.028). PMEL expression positively correlated with the tumor size of TSC-RAMLs, and inversely with the reduction rate of TSC-RAMLs after mTORC1 inhibitor treatment, which may suggest that PMEL may serve as a predictive biomarker for the efficacy of mTORC1 inhibitor treatment.

P3, N=12, Active, not recruiting, Rhythm Pharmaceuticals, Inc. | Completed --> Active, not recruiting | Trial completion date: Sep 2023 --> Sep 2024