Symposium
Plenary Hall: Lomond Auditorium
Plenary Hall: Lomond Auditorium
Saturday, June 27, 02:40 PM – 03:55 PM
SCNP-Selected Symposium 5:
Translational Therapeutic Discovery in Autism and Fragile X Syndrome
Translational Therapeutic Discovery in Autism and Fragile X Syndrome
The search for effective pharmacological treatments for autism has been long and challenging, with limited success to date. Currently, only aripiprazole and risperidone are approved for clinical use, and both target irritability rather than core symptoms of autism (1, 2).
Similarly, despite major advances in understanding the genetic and molecular mechanisms underlying Fragile X syndrome (FXS), no effective pharmacotherapy has yet been identified (2).
Several compounds, such as memantine, donepezil, and oxytocin, have shown encouraging results in preclinical studies but failed to demonstrate efficacy in late-stage clinical trials (3-10). These repeated setbacks underscore the urgent need for safe and effective treatments capable of modifying the core features of autism and FXS.
Translational neuroscience continues to drive the search for new therapeutic strategies for neurodevelopmental disorders. Indeed, this symposium will present three complementary approaches that bridge molecular mechanisms and behavioural outcomes, highlighting how integrative translational research can guide drug discovery for autism, FXS, and related conditions. The session will also illustrate how basic science discoveries can evolve into clinical development programs, as exemplified by the path leading to zatolmilast for FXS.
Mr. Michael Parkhill will present their work investigating cannabidiol (CBD) as a potential treatment for autism, building on its good tolerability and encouraging early results in FXS. Using two mouse models of syndromic autism (Shank3 and Fmr1 knockouts), this back-translational study examines whether CBD can ameliorate social deficits and repetitive behaviours. Furthermore, they explore CBD’s impact on hippocampal endocannabinoid signalling and gene expression.
Dr. Kevin Sanders will discuss the scientific trajectory that led to the development of zatolmilast, a negative allosteric PDE4D inhibitor, as an investigational treatment for FXS (11). Through collaboration among patient advocacy, FXS researchers, and the pharmaceutical industry, preclinical studies laid the foundation for early clinical testing and ultimately the initiation of a full registrational clinical development program aimed at delivering the first targeted FXS treatment to the community.
Dr. Ilse Gantois will present her research on the therapeutic effects of metformin, an FDA-approved drug, in treating symptoms associated with ASD, using mouse models of FXS and Phelan-McDermid syndrome (PMS; Shank3 knockout mice) in both males and females. Their mechanistic studies have implicated the ERK/MAPK and mTOR pathways, which control mRNA translation, and are overactivated in several brain areas of these mouse models.
Together, these talks integrate molecular, circuit-level, and pharmacological perspectives to identify new entry points for therapeutic development in autism and FXS. By linking mechanistic research with translational innovation, this symposium will highlight promising pathways for intervention and promote cross-disciplinary collaboration between basic scientists and clinical investigators.
Similarly, despite major advances in understanding the genetic and molecular mechanisms underlying Fragile X syndrome (FXS), no effective pharmacotherapy has yet been identified (2).
Several compounds, such as memantine, donepezil, and oxytocin, have shown encouraging results in preclinical studies but failed to demonstrate efficacy in late-stage clinical trials (3-10). These repeated setbacks underscore the urgent need for safe and effective treatments capable of modifying the core features of autism and FXS.
Translational neuroscience continues to drive the search for new therapeutic strategies for neurodevelopmental disorders. Indeed, this symposium will present three complementary approaches that bridge molecular mechanisms and behavioural outcomes, highlighting how integrative translational research can guide drug discovery for autism, FXS, and related conditions. The session will also illustrate how basic science discoveries can evolve into clinical development programs, as exemplified by the path leading to zatolmilast for FXS.
Mr. Michael Parkhill will present their work investigating cannabidiol (CBD) as a potential treatment for autism, building on its good tolerability and encouraging early results in FXS. Using two mouse models of syndromic autism (Shank3 and Fmr1 knockouts), this back-translational study examines whether CBD can ameliorate social deficits and repetitive behaviours. Furthermore, they explore CBD’s impact on hippocampal endocannabinoid signalling and gene expression.
Dr. Kevin Sanders will discuss the scientific trajectory that led to the development of zatolmilast, a negative allosteric PDE4D inhibitor, as an investigational treatment for FXS (11). Through collaboration among patient advocacy, FXS researchers, and the pharmaceutical industry, preclinical studies laid the foundation for early clinical testing and ultimately the initiation of a full registrational clinical development program aimed at delivering the first targeted FXS treatment to the community.
Dr. Ilse Gantois will present her research on the therapeutic effects of metformin, an FDA-approved drug, in treating symptoms associated with ASD, using mouse models of FXS and Phelan-McDermid syndrome (PMS; Shank3 knockout mice) in both males and females. Their mechanistic studies have implicated the ERK/MAPK and mTOR pathways, which control mRNA translation, and are overactivated in several brain areas of these mouse models.
Together, these talks integrate molecular, circuit-level, and pharmacological perspectives to identify new entry points for therapeutic development in autism and FXS. By linking mechanistic research with translational innovation, this symposium will highlight promising pathways for intervention and promote cross-disciplinary collaboration between basic scientists and clinical investigators.