From Animal Neurocognitive Trials to Humans: How Do We Find the Most Appropriate Outcome Measures and Trial Designs for Tuberous Sclerosis Complex and Other Genetic Disorders?

Tuberous Sclerosis Complex (TSC) has become a powerful model to study a range of TSC-associated neuropsychiatric disorders (TAND), including autism spectrum disorder (ASD) and specific neuropsychological deficits. Given the success of mTOR inhibitors to treat SEGA (subependymal giant cell astrocytomas) and renal angiomyolipomas, there has been growing interest in molecularly-targeted treatments of TAND. However, translation from animal trials to humans has not been straightforward in other genetic disorders such as Fragile X and Neurofibromatosis Type 1, in spite of strong pre-clinical findings. In this panel we will discuss translation from pre-clinical to clinical trials to consider possible challenges in this effort. Our first presentation will be a recent pre-clinical study of neurocognition and social behavior in the Tsc2+/- (Eker) rat. Next, we will explore current clinical trials of neurocognition and ASD in TSC and consider what we have learnt along the way. In the third presentation we will examine executive deficits in normally-intelligent adults with TSC to reflect on neuropsychological profiles and the impact of different analysis approaches. In our final talk, we will present a study of resting state EEG as potential biomarker for TSC-associated and non-syndromal ASD.
Friday, May 13, 2016: 3:30 PM-5:30 PM
Room 309 (Baltimore Convention Center)
Panel Chair:
P. J. de Vries
E. Berry-Kravis
3:30 PM
mTOR Inhibitor Reverses Autistic-like Behaviour in Tsc2+/- Rats with Developmental Epilepsy
M. Schneider P. J. de Vries K. Schönig V. Rößner R. Waltereit
3:55 PM
Clinical Investigations in TSC
M. Sahin M. Bebin J. Y. Wu H. Northrup A. W. Byars A. Sadhwani K. Kapur P. J. de Vries D. Krueger
4:45 PM
Recurrence Quantification Analysis of Resting State EEG As Risk Biomarker for Non-Syndromal and Syndromal ASD
T. M. Heunis C. Aldrich M. Nieuwoudt S. S. Jeste M. Sahin J. M. Peters P. J. de Vries