Researchers

Preclinical Research

To spur development of new ideas leading to novel drugs, the TS 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 TS 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.

Preclinical Timeline

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.

preclinicalconsortium

Preclinical Consortium Utilization by Industry and Academic Researchers

Chart last updated September 2018. Results from consortium-initiated “Bucket A” studies are available to all consortium members immediately after study completion. Results of “Bucket B” studies are released to the consortium after an initial escrow period. The results of “Bucket C” studies of proprietary compounds belong entirely to the initiating company.

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

Nominating Compounds for Testing

Nominations may be made anytime but will be evaluated in batches twice each year:

  • Submissions received on or before June 15 will be evaluated by July 31.
  • Submissions received on or before December 15 will be evaluated by February 15.

Compounds nominated may include:

  • Drugs with a rationale for re-purposing to treat TSC and which are in clinical development or marketed for other indications.
  • Analogs of existing drugs which may have improved efficacy or safety.
  • Tool compounds to investigate novel mechanisms of action.

Key Resources

Acknowledgments

The TSC Preclinical Consortium is coordinated and wholly funded by the TS 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:

Calvin Ho, PhD
Science Project Coordinator
Tuberous Sclerosis Alliance
801 Roeder Road, Suite 750
Silver Spring, MD  20910
Telephone:  1-800-225-6872 or 301-562-9890 ext. 205
E-mail: cho@tsalliance.org