Trailblazer Pilot Award: Dbr1 inhibitors: a novel drug treatment for the neurodegenerative disease ALS
By Kelly Hale, Marketing & Communications Specialist
Apr 22, 2024
Name: Thomas Menees, Ph.D., University of Missouri – Kansas City
Study Title: Dbr1 inhibitors: a novel drug treatment for the neurodegenerative disease ALS
Area of Eligibility: Drug and Medical Device Development
Thomas Menees’ project advances a promising drug therapy for amyotrophic lateral sclerosis, more commonly known as ALS or Lou Gehrig’s disease. Currently, there are no treatments that significantly alter the course of this disease, and death typically occurs within 2 – 5 years of diagnosis.
Most ALS cases are associated with aggregation, or clumping, of the RNA-binding protein TDP-43 inside motor neurons of the brain and spinal cord. TDP-43 aggregation is strongly correlated with motor neuron death, which results in loss of voluntary muscle movement and death of the ALS patient. Because cells require TDP-43 for survival, shutting off production of this protein is not a therapeutic option.
Menees’ collaborator, Aaron Gitler of Stanford University, discovered that inhibition of the RNA lariat debranching enzyme, Dbr1, suppresses TDP-43 aggregation. Menees studies the Dbr1 enzyme, which cuts looped RNA molecules called RNA lariats. Dbr1 inhibition causes RNA lariats to accumulate in cells and is well-tolerated at low levels.
Menees’ prior work led to the discovery that Dbr1 is required for replication of the AIDS virus, HIV. Since they were both working in the field around Dbr1, Menees and Gitler teamed up to identify Dbr1 inhibitors for treating ALS and HIV infection.
Since ALS is a rare disease with no truly effective treatments, Menees decided to focus his efforts on ALS and TDP-43 aggregation. Surprisingly, RNA lariats that accumulate during Dbr1 inhibition bind TDP-43 and prevent it from aggregating. Dbr1 inhibition also “dissolves” preexisting TDP-43 aggregates. Thus, Dbr1 inhibitors are a promising approach for developing a therapy to untangle TDP-43 aggregates in motor neurons.
Menees and Gitler identified three Dbr1 inhibitors out of a collection of 128,000 drug-like chemicals. Menees plans to carry the work forward by using the best inhibitor to develop a drug for ALS.
“We’re in the ‘Valley of Death’ stage right now in the drug development process,” Menees said. “This is where basic research discoveries that could help patients have advanced to a point where targeted, applied research funding is important, but hard to get. Our project will take our best Dbr1 inhibitor and design novel, more effective inhibitors that could slow or stop the progression of ALS.”
This project is a collaboration between the University of Missouri-Kansas City, Stanford University, and the University of Kansas.
Kelly Hale
Marketing & Communications Specialist
Latest Articles
View All
Funded Projects · News
Oct 02, 2025
Integrating Special Populations Trailblazer Award: Amy Bodde, Ph.D. and Brian Helsel, Ph.D.
TL1 Trainee · News
Sep 30, 2025
TL1 Postdoctoral Spotlight: Chase Sakitis, Ph.D., Children’s Mercy Kansas City
KL2 Scholar · News
Sep 09, 2025
KL2 Scholar Jess Meyer, Ph.D., KU Medical Center
Funded Projects · News
Sep 04, 2025
Biostatistics, Epidemiology, and Research Design Trailblazer Awardee: Kate Young
News
Aug 20, 2025
Hoglund Biomedical Imaging Center: New Director, New Location
TL1 Trainee · News
Jun 26, 2025
Brittany Martinez, Ph.D., Selected for Prestigious National Institutes of Health’s Clinical and Translational Research Summer Course
News
May 27, 2025
Luz Ortiz Joins Frontiers Clinical and Translational Science Institute
News
May 27, 2025
First Midwest Research Skills Development Workshop a Success
Funded Projects · News
May 06, 2025
Hyunjoon Kim, Ph.D., Institute for Advancing Medical Innovations Trailblazer Award
TL1 Trainee · News
Apr 29, 2025
TL1 Postdoctoral Trainee Alexandra Prosser-Dombrowski, M.D., Children’s Mercy Kansas City
Events
Apr 22, 2025
2025 Frontiers CTSI Research Symposium Photos
TL1 Trainee · News
Mar 25, 2025
TL1 Postdoctoral Trainee Spotlight Brittany Martinez, Ph.D., University of Kansas Medical Center
News
Mar 11, 2025
Following Up on TL1 Postdoctoral Scholar Kara Christensen Pacella, Ph.D.
TL1 Trainee · News
Feb 24, 2025
TL1 Postdoctoral Training Program Spotlight: Aaron Smith Ph.D., RD, University of Kansas Medical Center
KL2 Scholar · News
Jan 13, 2025
KL2 Scholar, April McNeill-Johnson, M.D., Children’s Mercy Kansas City
News
Jan 10, 2025
Frances M. Yang, Ph.D., Provides Expert Testimony as Part of White House Administration’s Gun Violence Prevention Initiative
KL2 Scholar · News
Jan 07, 2025
University of Kansas Medical Center Research Institute Receives a $245,000 Award for Project on Engaging Women in Research Post-Incarceration to be Led by Frontiers KL2 Scholar
Funded Projects · News
Dec 10, 2024
2024-2025 Broderick Crawford Community Research Partnership Awardees
News
Dec 05, 2024
Lisette Jacobson, Ph.D., MPA, M.A., using past Lauren S. Aaronson Pilot Award to Further Research Career in Helping to Improve Health in Rural and Urban Areas
TL1 Trainee · News
Dec 03, 2024
TL1 Predoctoral Program: Trenton Edwards, University of Kansas Medical Center, Wichita
Nov 07, 2024
Meet Frontiers Intern Sidney Johnson
TL1 Trainee · News
Nov 04, 2024
TL1 Predoctoral Program: Cole Bird, University of Kansas Medical Center
Services · News
Nov 04, 2024
Consultation Connection: How Obdulia Covarrubias, Ph.D., worked with Juntos to Help Move Her Research Study Forward
News
Oct 31, 2024
November Congratulations!
Funded Projects · News
Oct 23, 2024
Colby Souders, M.D. Receives Integrating Special Populations (ISP) Pilot Award
Funded Projects · News
Oct 08, 2024
Biostatistics, Epidemiology, and Research Design (BERD) Trailblazer Award
Funded Projects · News
Oct 07, 2024
Institute for Advancing Medical Innovations Trailblazer Awardee: Susana Chavez-Bueno, M.D., Children’s Mercy Kansas City
TL1 Trainee · News
Oct 01, 2024
TL1 Postdoctoral Trainee Landon Deru, Ph.D., MBA, ATC; University of Kansas Medical Center
KL2 Scholar · News
Sep 06, 2024
KL2 Scholar Kate Kyler, M.D., MSc, FAAP; Children's Mercy Kansas City
Funded Projects · News
Sep 03, 2024
Lauren S. Aaronson Pilot Award: Courtney Berrios, MSc, ScM, CGC
News
Aug 30, 2024
Alejandra Camacho-Soto, M.D., University of Kansas Medical Center
News
Aug 30, 2024
Abid Qureshi, M.D., University of Kansas Medical Center
News
Aug 30, 2024
Alexandra Prosser, M.D., Children’s Mercy Kansas City
News
Aug 30, 2024
Amy Smith, Ph.D., Children’s Mercy Kansas City
News
Aug 30, 2024
Anna Wallisch, Ph.D., University of Kansas Medical Center
News
Aug 30, 2024
Dana Bakula, Ph.D., Children’s Mercy Kansas City
News
Aug 30, 2024
Dhanushki Abeykoon, University of Kansas Medical Center/University of Kansas
News
Aug 30, 2024
Jephte Akakpo, Ph.D., University of Kansas Medical Center
News
Aug 30, 2024
Kathryn Unruh, Ph.D., University of Kansas
News
Aug 30, 2024
Rong Xin Liu, University of Kansas/University of Kansas Medical Center
News
Aug 30, 2024
Sarah Weinsztok, Ph.D., University of Kansas
News
Aug 30, 2024
April McNeill Johnson, M.D., Children’s Mercy Kansas City
News
Aug 27, 2024
Amanda Emerson, Ph.D., University of Kansas Medical Center
News
Aug 27, 2024
Rebecca Lepping, Ph.D., University of Kansas Medical Center
Funded Projects · News
Aug 27, 2024
Lauren S. Aaronson Pilot Awardee: Deanna Hanson-Abromeit, Ph.D., MT-BC, University of Kansas Lawrence.
Funded Projects · News
Aug 22, 2024
Lauren S. Aaronson Pilot Awardee: Emily Mailey, Ph.D., Kansas State University
KL2 Scholar · News
Aug 20, 2024
KL2 Scholar Alice Zhang, Ph.D., University of Kansas Medical Center
News
Aug 13, 2024
John A Taylor, III, MD, MS, Working on Next Phase of Potential Cancer Treatment Thanks to Grant from the Department of Defense
News
Jul 31, 2024
Frontiers Scholars Club: Empowering the Next Generation of Clinical Translational Scientists
News
Jul 26, 2024
Broderick Crawford Community Partnership Awardee: John Tumberger (Project Leader) and Stephani Stancil, Ph.D., APRN (Project Mentor and PI)
News
Jul 22, 2024
Amy Bodde, Ph.D., MPH, to Pave the Way for Groundbreaking Alzheimer's Intervention Tailored for Down Syndrome Adults
KL2 Scholar · News
Jul 11, 2024
KL2 Spotlight: Alejandra Camacho-Soto, M.D., MPHS, University of Kansas Medical Center
KL2 Scholar
Jul 02, 2024
KL2 Spotlight: Bethany Forseth, Ph.D., University of Kansas Medical Center
News
Jun 18, 2024
Former KL2 Scholar Stephani Stancil, Ph.D., APRN, Involved in Multiple Projects
News
Jun 10, 2024
Former KL2 Scholar Jennifer Villwock, M.D., FAAOA, Working on Multiple Research Projects, Mentoring a TL1 Trainee
KL2 Scholar · News
Jun 05, 2024
Frontiers Clinical and Translational Science Institute KL2 Scholar Amanda Emerson, Ph.D., RN, Receives Prestigious Fellowship
News
Jun 04, 2024
Catching up with Robin Shook, Ph.D., Children’s Mercy Kansas City
News · In the Community · Funded Projects
Jun 04, 2024
Broderick Crawford Community-Partnership Award: Dola Williams with ICanSir!
Funded Projects · News
May 20, 2024
Broderick Crawford Community Partnership Award: Bringing Lupus Survivors and Physician Researchers Together to Develop, Foster Understanding and Improve Outcomes
Funded Projects · News
May 17, 2024
2023 Institute for Advancing Medical Innovation Trailblazer Pilot Award
Funded Projects · News
May 16, 2024
Biostatistics, Epidemiology and Research Design Pilot Award
Funded Projects · News
May 08, 2024
Advancing Medical Innovation Trailblazer Project Title: SH3BP2 inhibitors to target SH3BP2-mediated immune activation in nephrotic syndrome
News
Apr 25, 2024
Ana S.A. Cohen, Ph.D., FACMG - Investigating How to Expand Genetic Testing for Rare Diseases in Rural Areas
Funded Projects · News
Apr 22, 2024
Trailblazer Pilot Award: Dbr1 inhibitors: a novel drug treatment for the neurodegenerative disease ALS
Apr 10, 2024
2024-2025 KL2 Scholars and TL1 Trainees
TL1 Trainee · News
Mar 07, 2024
Spotlight on Dhanushki Abeykoon, TL1 Trainee and PharmD student
Funded Projects · News
Mar 05, 2024
Developing thermal imaging as a biomarker to augment “remote visits” where physical exams are not possible
Events · News
Feb 29, 2024
2024 Research Symposium
Funded Projects · News
Feb 19, 2024
Lauren S. Aaronson Frontiers Pilot Awardee
Feb 19, 2024
Lauren S. Aaronson Frontiers Pilot Awardee - Kai Ling Kong
Funded Projects · News
Feb 19, 2024
Lauren S. Aaronson Frontiers Pilot Awardee - Marion Leaman, Ph.D. CCC-SLP
TL1 Trainee · News
Feb 08, 2024
Spotlight on Rong Xin Liu, TL1 Pre-Doctoral Trainee
News · In the Community · Funded Projects
Feb 06, 2024
Integrating Special Populations Pilot Award
Funded Projects · News
Jan 09, 2024
Catching Up with Kelsie Forbush, Ph.D., past Trailblazer Pilot Awardee
KL2 Scholar · News
Jan 09, 2024
Spotlight on TL1 Program's Amy Smith, Ph.D., Children's Mercy Kansas City
TL1 Trainee · News
Dec 07, 2023
Spotlight on Alexandra Prosser, M.D., TL1 Postdoctoral Trainee
News
Nov 30, 2023
Learn More About the Implementation Science Core
News
Nov 27, 2023
Frontiers Annual Impact Report 2023
KL2 Scholar · News
Nov 06, 2023
Spotlight on KL2 scholar April McNeill-Johnson, M.D.
TL1 Trainee · News
Nov 02, 2023
Spotlight on TL1 Postdoctoral Trainee Sarah Weinsztok, Ph.D.
News
Oct 24, 2023
Frontiers Annual Member Survey
News
Oct 03, 2023
Meet Shelby Williams, Administrative Director, Clinical and Translational Science Units at Rainbow, Fairway and Swope (University of Kansas Medical Center)
Funded Projects · News
Oct 03, 2023
Catching Up with Diego Mazzotti, Ph.D., a past Pilot Awardee
Events · News
Oct 03, 2023
KL2 Spotlight: Kathryn Unruh, Ph.D., University of Kansas – Lawrence
Sep 22, 2023
Former Frontiers KL2 Scholar Stephani Stancil, PhD, APRN Presenting at K-CART Research Seminar
KL2 Scholar · News
Sep 07, 2023
KL2 Spotlight: Rebecca Lepping, Ph.D., University of Kansas Medical Center
News
Sep 05, 2023
Getting to Know Matthew Mosconi, Ph.D. New Co-Lead for Frontiers KL2 Scholars program
Aug 29, 2023
KU Center for Community Access, Rehabilitation Research, Education and Service (KU CARES)
Funded Projects · News
Aug 29, 2023
Catching Up with Anthony Fehr, Ph.D.
News
Aug 08, 2023
Informatics Collaboration
Partner News · News
Jul 28, 2023
T32 Post-doc Fellowship in Cardiovascular Outcomes Research
News · In the Community
Jul 26, 2023
Juntos Back to School Event
Jul 18, 2023
10 Questions with Nicole Nuckolls, Ph.D.
0
Jul 17, 02023
Garold Minns, M.D., Dean, School of Medicine, Wichita
Funded Projects · News
Jul 10, 2023
Catching Up with Jingxin Wang, Ph.D., past Frontiers Pilot Awardee
Funded Projects · News
Jul 05, 2023
Catching up with Shyam Sathyamoorthi, M.D., Ph.D.
News
Jul 03, 2023
Catching up with Valentina (Tina) Shakhnovich, M.D.
Funded Projects · News
Jul 01, 2023
Catching up with Jonathan Wagner, D.O., FAAP, Children’s Mercy Kansas City
Funded Projects · News
Jun 27, 2023
Frontiers Integrating Special Populations Pilot Award
News
Jun 27, 2023
10 Questions with Maggie Padek Kalman
Events · News
Jun 27, 2023
Congratulations to Stephani Stancil, Ph.D., APRN on her K23 Award!
TL1 Trainee · News
Jun 08, 2023
Spotlight on TL1 Predoctoral Trainee Jada Ohene-Agyei
TL1 Trainee · News
Jun 06, 2023
Spotlight on TL1 Pre-Doctoral Trainee Sarah Johnson
News
Jun 01, 2023
Meet Frontiers Recruitment and Network Navigator Hanluen Kuo
Funded Projects · News
May 25, 2023
Catching Up with Jenny Robinson, former Pilot Awardee (2020-2021)
News
May 09, 2023
Meet Frontiers Administrative Coordinator Christie Smith
Partner News · News
May 04, 2023
Spotlight on Trisha Steele, Administrative Director, Center for Clinical Research, University of Kansas School of Medicine – Wichita
TL1 Trainee · News
May 02, 2023
Spotlight on TL1 Post-doctoral Trainee Stacey Aaron, Ph.D.
Events · News
Apr 21, 2023
2023 Research Symposium Presentations
KL2 Scholar · News
Apr 04, 2023
Spotlight on KL2 Scholar Dana Bakula, Ph.D.
News
Apr 04, 2023
Meet Frontiers Community Partner Project Manager Cherayla Haynes
TL1 Trainee · News
Apr 04, 2023
Spotlight on TL1 Postdoctoral Trainee Brian Helsel, Ph.D., MS, CSCS
News · KL2 Scholar
Mar 30, 2023
John Hopkins Virtual Nursing Grand Rounds
Mar 28, 2023
New Genomics Resource!
TL1 Trainee · News
Mar 28, 2023
New TL1 Co-Lead: Nicole Nollen, B.S., M.A., Ph.D
Events · News
Mar 23, 2023
2023 Research Symposium photos
News
Mar 02, 2023
Research Spotlight – Olivia Veatch, Ph.D.
News
Feb 22, 2023
"Communicating Research to the Community" Program Documents and Links
Feb 17, 2023
“Cuídate, Chécate y Muévete” (Care of yourself, Take the test, Move your body)
Feb 14, 2023
Research Symposium Poster Presentation
News
Feb 07, 2023
Using Your Resources: University of Kansas Medical Center A. R. Dykes Library
Feb 07, 2023
Spotlight: John Thyfault, Ph.D., FACSM, FTOS and the University of Kansas Diabetes Institute
40
Feb 03, 02023
Why Is It Important to Collaborate?
News
Feb 02, 2023
Spotlight on Tiffany Schwasinger-Schmidt, M.D., Ph.D., FACP
News
Jan 24, 2023
Frontiers Has an Associate Director Opening
TL1 Trainee · News
Jan 17, 2023
Spotlight on TL1 Trainee Jephte Akakpo, Ph.D.
News
Jan 05, 2023
Spotlight on Robert White, Ph.D., MS – Dean of the College of Biosciences at Kansas City University (KCU)
Funded Projects · News
Jan 05, 2023
Spotlight on Olivia Veatch, Ph.D., MS
News · In the Community
Jan 04, 2023
Community Partner Spotlight: Dr. Jennifer Bacani McKenney
Dec 21, 2022
JUNTOS December Community Events
Funded Projects · News
Dec 19, 2022
Frontiers Clinical and Translational Science Institute gives six Pilot Awards
In the Community
Dec 15, 2022
JUNTOS Community Events
News · In the Community · Partner News
Dec 09, 2022
Spotlight on Andrea Bradley Ewing, MPA, MA; Community Engaged Research, Health Services and Outcomes Research; Children’s Mercy Kansas City
KL2 Scholar · News
Dec 08, 2022
Spotlight on KL2 Scholar Anna Wallisch, Ph.D.
News · In the Community
Dec 06, 2022
Community Partner Broderick Crawford Passes Away
Events · News · Services
Dec 05, 2022
First Frontiers Mock Study Section
Funded Projects · News
Dec 01, 2022
Spotlight on Rebecca Lepping, Ph.D.
Nov 28, 2022
Frontiers New Tagline
KL2 Scholar · Funded Projects · News
Nov 08, 2022
Spotlight on KL2 Scholar Stephani Stancil, Ph.D., APRN
TL1 Trainee · Funded Projects · News
Nov 08, 2022
Spotlight on TL1 Post-Doctoral Trainee Elly Leavens, Ph.D.
News
Nov 04, 2022
Focus on Research Informatics with Erin Nichols, Director of Research Informatics -University of Kansas Health System
News
Nov 03, 2022
Call for Abstracts and Case Reports
KL2 Scholar · Funded Projects
Oct 14, 2022
Meet KL2 Scholar Romina Barral, M.D.
KL2 Scholar · Funded Projects
Oct 10, 2022
Meet KL2 Scholar Amanda Emerson
Events · News
Sep 28, 2022
Frontiers Celebrates Award Renewal
News
Sep 21, 2022
University of Kansas Medical Center announces nearly $27 million NIH grant to accelerate clinical and translational research in the region
KL2 Scholar · Funded Projects
Aug 12, 2022
Spotlight on KL2 program recipient, Jennifer Villwock, M.D.
News
Aug 04, 2022
Kansas IDeA Network Provides Another Round of Funding
Funded Projects
Jul 13, 2022
Spotlight on Heather Minchew
Jul 11, 2022
Fosociclopirox AUA Thought Leadership Series
TL1 Trainee
Jun 14, 2022
Spotlight on Bertha De Los Santos, KU PharmD Student
News
Jun 14, 2022
Women Making a Difference in Research
Funded Projects
Apr 28, 2022
Trainees at ACTS conference
Oct 29, 2021
Laura Mussulman, MA, MPH, Named Director of Clinical and Translational Science Unit Fairway
Sep 17, 2021
Researchers at 3 CTSA Institutions Collaborate to Develop a Research Network Supporting Translational Science Across the Criminal Justice Continuum
