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Preclinical research

The TSC Alliance and the Preclinical Consortium have been instrumental partners in establishing the preclinical models and data necessary for development of our candidate therapeutic. The historical data sets, knowledge of the models, and connection with the CROs running the models have helped guide our team about what constitutes a successful treatment, and we are optimistic for the path forward.”

Patrick Sarmiere, VP of Preclinical Development, Ovid Therapeutics

The TSC Preclinical Consortium is a partnership with TSC researchers in industry and academia, designed to facilitate the evaluation of novel and repurposed therapeutics for their effectiveness and safety in animal models of TSC.  The goal is to advance those therapeutics with compelling effectiveness and safety are advanced to clinical trials.

The Preclinical Consortium approach

Directed by Dean Aguiar, PhD, (Vice President, Translational Research) who has more than 20 years in drug design from his previous work in pharma and scientific foundations, the consortium delivers quality in drug testing by:

  • Ensuring the reproducibility of models and assays
  • License negotiation and management 
  • Study oversight for quality control
  • Data interpretation assistance  

TSC Alliance-funded testing opportunities

All members can propose compounds for testing and benefit from the shared data generated by TSC Alliance funded studies.

  • Compound nomination form (to be reviewed twice yearly)  
  • PIs have the ability to publish first and have first right of refusal for biospecimens from their proposed study

 

Confidential drug screening

Company Members have the option to remain anonymous and retain confidentiality and ownership of data by paying for experiments as defined in the Consortium Operating Agreement.  Testing of compounds is performed directly through the TSC Alliance and contract research organization providers. Under the Consortium Operating Agreement, the TSC Alliance assumes no intellectual property rights for industry-sponsored work.  

The models

The different manifestations of TSC — such as tumors kidneys as well as epilepsy — are modeled in mice using different genetic manipulations. We also have many murine biospecimens held at our repository at the Van Andel Institute including liver, kidney, brain and plasma.  

Epilepsy and behavior

  • Capability for 24/7 EEG monitoring and analysis with our partner contract research organization, PsychoGenics, Inc.  
  • On-demand breeding at the same facility as EEG 

Models

Future Models

Tumor

  • Longitudinal tumor volume measurement and other assays done with our partner contract research organization, Porsolt
  • On-demand breeding at the same facility

Models

Future Models

  • Lymphangioleiomyomatosis (LAM) via ELT3 or 105k cell injection 

Other models 

The Preclinical Consortium has unique ability to bring on additional models and assays to meet the research needs of our partners. We achieve this transgenic work through our partnership with the Van Andel Institute. 

Recent publications

Researchers conducting studies with the TSC Preclinical Consortium have published several articles in well-regarded, peer-reviewed biomedical journals, including:

  • Shrestha, S., et al. Angiotensin II receptor type 1 blockade regulates Klotho expression to induce TSC2-deficient cell death. doi.org/10.1016/j.jbc.2022.102580
  • Agarwal S., et al. Defining the Magnetic Resonance Features of Renal Lesions and Their Response to Everolimus in a Transgenic Mouse Model of Tuberous Sclerosis Complex. doi.org/10.3389/fonc.2022.851192
  • Nguyen, LH., et al. Inhibition of MEK-ERK signaling reduces seizures in two mouse models of tuberous sclerosis complex. doi.org/10.1016/j.eplepsyres.2022.106890
  • Vaughan, RM., et al. Chemical Biology Screening Identifies a Vulnerability to Checkpoint Kinase Inhibitors in TSC2-Deficient Renal Angiomyolipomas. doi.org/10.3389/fonc.2022.852859

Leadership groups

Steering Committee

  • Dean Aguiar, PhD, TSC Alliance
  • Tami Brtan, TSC Community
  • Lisa Henske, MD, Brigham and Women’s Hospital
  • Will Hind, PhD, Jazz Pharmaceuticals
  • Dominique Pichard, MD, National Center for Advancing Translational Sciences
  • Mustafa Sahin, MD, PhD, Boston Children’s Hospital
  • Peter Tsai, MD, PhD, University of Texas, Southwestern
  • Michael Wong, MD, PhD, Washington University, St. Louis

Advisors

  • Daniela Brunner, PhD, Psychogenics, Inc.
  • Richard Mushlin, PhD, Statistics Consultant
  • Maria Beconi, PhD, Pharmacokinetics Consultant

For inquiries, contact:

Dean J. Aguiar, PhD, Vice President, Translational Research at daguiar@tscalliance.org or Zoë Fuchs, Manager, Translational Research at zfuchs@tscalliance.org.

Acknowledgments

The TSC Preclinical Consortium is coordinated and wholly funded by the TSC Alliance thanks to generous support from the Gerry and Bill Cowlin Foundation, Drs. Bonnie and Jonathan Rothberg & Family, and many additional donors through the Unlock the Cure campaign. Company Members also support the Consortium through membership fees. 

The TSC Alliance is proud to partner with the following Contract Research Organizations to conduct our studies.