CN-105, an Apolipoprotein E Mimetic Peptide, and Its Impact on Postoperative Delirium in Elderly Patients: Insights from the Phase 2 MARBLE Study - Report - MDSpire

CN-105, an Apolipoprotein E Mimetic Peptide, and Its Impact on Postoperative Delirium in Elderly Patients: Insights from the Phase 2 MARBLE Study

  • By

  • Noah J. Timko

  • Mary Cooter Wright

  • Melody R. Smith

  • Piper C. Boykin

  • Jacqueline M. Emerson

  • Marty G. Woldorff

  • Sarada Eleswarpu

  • J. Taylor Herbert

  • Eugene W. Moretti

  • Michael J. Devinney

  • Chakib M. Ayoub

  • Frank W. Rockhold

  • David Ryu

  • Ayesha Syed

  • Keith W. VanDusen

  • Thomas Bunning

  • Bethany J. Hsia

  • Michael P. Bolognesi

  • William A. Jiranek

  • Henrik Zetterberg

  • Kaj Blennow

  • Janet L. Huebner

  • Zhong Li

  • Tyler H. Reekes

  • Jeffrey N. Browndyke

  • Daniel T. Laskowitz

  • Miles Berger

  • MARBLE Study Investigators

  • Michael R. Abern

  • Leah C. Acker

  • Samuel B. Adams

  • Peter J. Allen

  • Cindy L. Amundsen

  • Oke A. Anakwenze

  • Pallavi Avasarala

  • Matthew D. Barber

  • Andrew Berchuck

  • Daniel G. Blazer

  • Rachele Brassard

  • Brian E. Brigman

  • W.M. Bullock

  • Roberto Cabeza

  • Morgan A. Caldwell

  • Soren K. Christensen

  • Catharina C. Eisdorfer

  • Lori Cole-Freiburger

  • Brian J. Colin

  • Mitchell W. Cox

  • Donna M. Crabtree

  • Thomas A. D’Amico

  • Brittany A. Davidson

  • James K. DeOrio

  • Mark E. Easley

  • Clay Elliott

  • Detlev Erdmann

  • Melissa M. Erickson

  • Alisan Fathalizadeh

  • Michael N. Ferrandino

  • Robert D. Fitch

  • Howard W. Francis

  • Matthew Fuller

  • John C. Haney

  • David H. Harpole

  • Bonita L. Hilliard

  • Julia Hoang

  • Jeffrey C. Gadsden

  • Mark J. Gage

  • Arun Ganesh

  • Jaleesa Garner

  • Jeffrey R. Gingrich

  • Summer Granger

  • Rachel A. Greenup

  • Christine Ha

  • Ashraf S. Habib

  • Ralph Abi Hachem

  • Ashley E. Hall

  • Matthew G. Hartwig

  • Laura J. Havrilesky

  • Mitchell T. Heflin

  • Tarrah Henley

  • Scott T. Hollenbeck

  • Thomas J. Hopkins

  • Brant A. Inman

  • David W. Jang

  • Russel R. Kahmke

  • Isaac O. Karikari

  • Nicholas Kathrein

  • Amie Kawasaki

  • Deborah R. Kaye

  • Hadiza S. Kazaure

  • Josiane Kerbage

  • Jacob A. Klapper

  • Christopher S. Klifto

  • Rebecca Klinger

  • Stuart J. Knechtle

  • Sandhya A. Lagoo-Deenadayalan

  • Billy Y. Lan

  • Paula S. Lee

  • Walter T. Lee

  • Howard Levinson

  • Brian D. Lewis

  • Michael E. Lidsky

  • Janice Lim

  • Michael E. Lipkin

  • Andrew J. Liu

  • Christopher R. Mantyh

  • Jeffrey R. Marcus

  • Hector F. Martinez-Wilson

  • Shelley R. McDonald

  • Jennifer L. McNally

  • Nitin L. Mehdiratta

  • John Migaly

  • Timothy E. Miller

  • Suhail K. Mithani

  • Sean P. Montgomery

  • Paul J. Mosca

  • Judd W. Moul

  • David M. Murdoch

  • Devika Naphade

  • Christine L. Nelson

  • Thomas L. Novick

  • Daniel P. Nussbaum

  • Brian J. Ohlendorf

  • Steven A. Olson

  • Isaac Oyediran

  • Theodore N. Pappas

  • John J. Park

  • Ashley B. Parker

  • Andrew C. Peterson

  • Christy E. Peterson

  • Brett T. Phillips

  • Thomas J. Polascik

  • Peter T. Potash

  • Glenn M. Preminger

  • Rebecca A. Previs

  • Kadiyala V. Ravindra

  • Sydney M. Record

  • Aparna S. Rege

  • Kristen M. Rezak

  • Kenneth C. Roberts

  • Cary N. Robertson

  • Daniel J. Rocke

  • David S. Ruch

  • Sean P. Ryan

  • Charles D. Scales

  • Randall P. Scheri

  • Angeles A. Secord

  • Keri A. Seymour

  • Ankeet M. Shah

  • Kevin N. Shah

  • Nazema Y. Siddiqui

  • Geoffroy C. Sisk

  • Shayan Smani

  • Kevin W. Southerland

  • Courtney H. Stanczak

  • Michael T. Stang

  • Samuel D. Stanley

  • Niccolò Terrando

  • Julie K. M. Thacker

  • Brittany N. Thomas

  • Jake P. Thomas

  • Yanne Toulgoat-DuBois

  • Daniel C. Villalobos

  • Anthony G. Visco

  • Alison C. Weidner

  • John Whittle

  • David A. Williams

  • Megan Wong

  • Mamata Yanamadala

  • Rosa O. Yang

  • Christopher C. Young

  • Mary Yurashevich

  • Sabino Zani

  • Daphne Zhu

  • April 3, 2026

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Clinical Report: CN-105 and Its Impact on Postoperative Delirium in Elderly Patients

Overview

Expand on specific outcomes measured in the trial regarding delirium incidence and severity.

Background

Postoperative delirium (POD) is a prevalent complication among older adults, leading to increased morbidity, prolonged hospital stays, and higher healthcare costs. Current treatment options are limited, with no FDA-approved drugs available, highlighting the need for effective preventive strategies. Understanding the role of neuroinflammation in POD may provide insights into new therapeutic approaches, such as the use of CN-105.

Data Highlights

The MARBLE trial enrolled 67 patients, with 50 receiving CN-105 and 17 receiving placebo. The study was designed to assess the safety and feasibility of CN-105 in reducing delirium incidence and severity.

Key Findings

  • Delirium is a common postoperative complication in older adults, linked to increased mortality and healthcare costs.
  • Neuroinflammation is a key factor in the development of delirium, with the APOE ε4 allele being a significant risk factor.
  • CN-105, a peptide derived from the apoE receptor-binding domain, can cross the blood-brain barrier and may mitigate neuroinflammation.
  • The MARBLE trial was a triple-blind, placebo-controlled study conducted at Duke University Medical Center.
  • Safety and tolerability of CN-105 were established in phase 1 studies prior to the MARBLE trial.
  • The trial was not powered to assess dose-specific effects but aimed to compare combined CN-105 doses against placebo.

Clinical Implications

The findings from the MARBLE trial suggest that CN-105 may offer a novel approach to reducing the incidence of postoperative delirium in older adults by targeting neuroinflammation. Clinicians should consider the potential of such therapies in the perioperative management of at-risk populations.

Conclusion

Highlight the necessity for larger trials to confirm findings and assess long-term effects.

References

  1. Author(s)/Org, Source, Year -- Title
  2. BMC Psychiatry (Springer) — Machine Learning-Based prediction models for postoperative delirium: a systematic review and Meta-Analysis
  3. Retinal Physician — Clinical Trial Update April 2023
  4. Intensive Care Medicine — Comparative Analysis of Natural Language Processing and Confusion Assessment Method for Identifying Behavioral Disturbances in ICU Patients: Prevalence, Patient Profiles, Overlap, and Links to Treatment Outcomes
  5. Intensive Care Medicine — Evaluating Melatonin's Role in Delirium Prevention Among Mechanically Ventilated ICU Patients: Results from a Multi-Arm, Multi-Stage Adaptive Randomized Controlled Trial (DEMEL)
  6. Machine Learning-Based prediction models for postoperative delirium: a systematic review and Meta-Analysis
  7. Clinical Trial Update April 2023
  8. Comparative Analysis of Natural Language Processing and Confusion Assessment Method for Identifying Behavioral Disturbances in ICU Patients
  9. Postoperative Delirium in Older Adults Undergoing Noncardiac Surgery
  10. https://academic.oup.com/ageing/article-pdf/55/3/afag068/67658955/afag068.pdf
  11. Apolipoprotein E Mimetic Peptide CN-105 and Postoperative Delirium in Older Patients: The Phase 2 MARBLE Randomized Clinical Trial | Anesthesiology | JAMA Network Open | JAMA Network

Original Source(s)

CN-105, an Apolipoprotein E Mimetic Peptide, and Its Impact on Postoperative Delirium in Elderly Patients: Insights from the Phase 2 MARBLE Study

  • by Noah J. Timko, Mary Cooter Wright, Melody R. Smith, Piper C. Boykin, Jacqueline M. Emerson, Marty G. Woldorff, Sarada Eleswarpu, J. Taylor Herbert, Eugene W. Moretti, Michael J. Devinney, Chakib M. Ayoub, Frank W. Rockhold, David Ryu, Ayesha Syed, Keith W. VanDusen, Thomas Bunning, Bethany J. Hsia, Michael P. Bolognesi, William A. Jiranek, Henrik Zetterberg, Kaj Blennow, Janet L. Huebner, Zhong Li, Tyler H. Reekes, Jeffrey N. Browndyke, Daniel T. Laskowitz, Miles Berger, MARBLE Study Investigators, Michael R. Abern, Leah C. Acker, Samuel B. Adams, Peter J. Allen, Cindy L. Amundsen, Oke A. Anakwenze, Pallavi Avasarala, Matthew D. Barber, Andrew Berchuck, Daniel G. Blazer , Rachele Brassard, Brian E. Brigman, W.M. Bullock, Roberto Cabeza, Morgan A. Caldwell, Soren K. Christensen, Catharina C. Eisdorfer, Lori Cole-Freiburger, Brian J. Colin, Mitchell W. Cox, Donna M. Crabtree, Thomas A. D’Amico, Brittany A. Davidson, James K. DeOrio, Mark E. Easley, Clay Elliott, Detlev Erdmann, Melissa M. Erickson, Alisan Fathalizadeh, Michael N. Ferrandino, Robert D. Fitch, Howard W. Francis, Matthew Fuller, John C. Haney, David H. Harpole, Bonita L. Hilliard, Julia Hoang, Jeffrey C. Gadsden, Mark J. Gage, Arun Ganesh, Jaleesa Garner, Jeffrey R. Gingrich, Summer Granger, Rachel A. Greenup, Christine Ha, Ashraf S. Habib, Ralph Abi Hachem, Ashley E. Hall, Matthew G. Hartwig, Laura J. Havrilesky, Mitchell T. Heflin, Tarrah Henley, Scott T. Hollenbeck, Thomas J. Hopkins, Brant A. Inman, David W. Jang, Russel R. Kahmke, Isaac O. Karikari, Nicholas Kathrein, Amie Kawasaki, Deborah R. Kaye, Hadiza S. Kazaure, Josiane Kerbage, Jacob A. Klapper, Christopher S. Klifto, Rebecca Klinger, Stuart J. Knechtle, Sandhya A. Lagoo-Deenadayalan, Billy Y. Lan, Paula S. Lee, Walter T. Lee, Howard Levinson, Brian D. Lewis, Michael E. Lidsky, Janice Lim, Michael E. Lipkin, Andrew J. Liu, Christopher R. Mantyh, Jeffrey R. Marcus, Hector F. Martinez-Wilson, Shelley R. McDonald, Jennifer L. McNally, Nitin L. Mehdiratta, John Migaly, Timothy E. Miller, Suhail K. Mithani, Sean P. Montgomery, Paul J. Mosca, Judd W. Moul, David M. Murdoch, Devika Naphade, Christine L. Nelson, Thomas L. Novick, Daniel P. Nussbaum, Brian J. Ohlendorf, Steven A. Olson, Isaac Oyediran, Theodore N. Pappas, John J. Park, Ashley B. Parker, Andrew C. Peterson, Christy E. Peterson, Brett T. Phillips, Thomas J. Polascik, Peter T. Potash, Glenn M. Preminger, Rebecca A. Previs, Kadiyala V. Ravindra, Sydney M. Record, Aparna S. Rege, Kristen M. Rezak, Kenneth C. Roberts, Cary N. Robertson, Daniel J. Rocke, David S. Ruch, Sean P. Ryan, Charles D. Scales, Randall P. Scheri, Angeles A. Secord, Keri A. Seymour, Ankeet M. Shah, Kevin N. Shah, Nazema Y. Siddiqui, Geoffroy C. Sisk, Shayan Smani, Kevin W. Southerland, Courtney H. Stanczak, Michael T. Stang, Samuel D. Stanley, Niccolò Terrando, Julie K. M. Thacker, Brittany N. Thomas, Jake P. Thomas, Yanne Toulgoat-DuBois, Daniel C. Villalobos, Anthony G. Visco, Alison C. Weidner, John Whittle, David A. Williams, Megan Wong, Mamata Yanamadala, Rosa O. Yang, Christopher C. Young, Mary Yurashevich, Sabino Zani, Daphne Zhu

  • April 3, 2026

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