Preclinical Research

To spur development of new ideas leading to novel drugs, the TSC Alliance funds research grants to help learn more about the mechanisms of pathology in TSC. To facilitate the translation of basic and mechanistic research into clinical trials and new treatments for TSC, the TSC Alliance created a TSC Preclinical Consortium in collaboration with industry and academia to test the efficacy of candidate therapeutic drugs and advance the best to the clinical stage.

The Preclinical Consortium

The Preclinical Consortium engages academic and pharmaceutical industry researchers to help accelerate development of new therapies for TSC. A Steering Committee sets the long-term goals and priorities. Working Groups decide the best models and experimental designs for drug testing and provide oversight for rigorous quality control and interpretation of results. By using robust and reproducible models, protocols, and assays, the Preclinical Consortium ensures data are comparable from experiment to experiment. Compounds are handled and tested by experienced providers, and data are shared with all members of the consortium.

Members belong to industry, academia, or nonprofit organizations. All members can propose compounds for the screen and benefit from the shared data. Additionally, Company Members may submit compounds for testing and retain confidentiality and ownership of data by paying for experiments as defined in the Consortium Operating Agreement.


The Models

The different manifestations of TSC — such as tumors in the lungs and kidneys as well as epilepsy — can be modeled in mice using different genetic manipulations. The Preclinical Consortium has implemented the following models covering different aspects of TSC, namely epilepsy and tumors. Other models will be added as necessary for future studies.

Epilepsy: Tsc1flox/flox;GFAP-Cre+ (GFAP-Tsc1-CKO) mice

  • Video-EEG for seizure frequency
  • Treatment can begin at any age
  • Survival can be used as an alternative endpoint
  • Tissues can be collected for analysis of target protein or biomarkers of interest

Tumor (graft): 105K (Tsc2-null) mouse cell subcutaneous grafts in mice

  • Longitudinal tumor volume measurement by caliper
  • Tumors and organs can be collected at termination for histology or molecular studies
  • Treatment typically begins when tumor size reaches >100 mm3

Tumor (spontaneous): Tsc2+/- A/J mouse renal cystadenoma model

  • Tumor score based on size and cellularity determined by histology
  • Treatment typically begins at 5 months of age


The TSC Preclinical Consortium is coordinated and wholly funded by the TSC Alliance thanks to generous support from the Cowlin Family Fund, The Engles Collaborative Research Fund and many additional donors through the Unlock the Cure campaign. Company Members also support the Consortium through membership fees.

For Inquiries, Contact:

Dean J. Aguiar, PhD
Vice President, Translational Research
TSC Alliance
8737 Colesville Road, Suite 400
Silver Spring, MD  20910
Telephone:  1-800-225-6872 or 301-562-9890 ext. 219
E-mail: daguiar@tscalliance.org

Leadership Groups

Steering Committee

  • Véronique André, UCB
  • Martina Bebin, University of Alabama at Birmingham
  • Dean Aguiar, TSC Alliance
  • Lisa Henske, Brigham and Women’s Hospital
  • David Kwiatkowski, Brigham and Women’s Hospital
  • Laura Lubbers, CURE
  • John McCall, PharMac Consulting
  • Steve Roberds, TSC Alliance
  • Ben Whalley, GW Pharmaceuticals
  • Mike Wong, Washington University


  • Daniela Brunner, Senior Scientific Advisor, TSC Alliance
  • Richard Mushlin, Statistics Consultant
  • Maria Beconi, Pharmacokinetics Consultant

Functional (Neuro) Working Group

  • Angelique Bordey, Yale University
  • Kevin Ess, Vanderbilt University
  • Michael Gambello, Emory University
  • Kate Nichol, Greenwich Biosciences
  • Mustafa Sahin, Boston Children’s Hospital
  • Mike Wong, Washington University

Pathology (Tumor) Working Group

  • Lisa Henske, Brigham and Women’s Hospital
  • David Kwiatkowski, Brigham and Women’s Hospital
  • Hilaire Lam, Brigham and Women’s Hospital
  • Jeff MacKeigan, Michigan State University
  • Brendan Manning, T.H. Chan Harvard School of Public Health
  • Wei Shi, University of Southern California