APC cKO mouse as a new model of infantile spasms
Chris Dulla (Tufts University)
Identifying new therapies for infantile spasms
Aristea Galanopoulou (Albert Einstein College of Medicine)
Dr. Galanopoulou and her collaborators, Solomen Moshé, MD (Albert Einstein College of Medicine), James Cloyd, Pharm D and Lisa Coles, PhD (University of Minnesota), have obtained evidence for several new promising therapies with rapid onset efficacy on spasms in a chronic rat model of infantile spasms. The investigators are currently evaluating whether these new investigative drugs also improve neurodevelopmental outcomes and prevent epilepsy in their rat model of spasms.
Infantile Spasms Syndrome: From gene to bedside, an accelerated path to new therapy
Jeff Noebels (Baylor College of Medicine)
Inherited infantile spasms syndrome (ISS) is an uncommon yet catastrophic epilepsy with motor spasms, seizures, and intellectual disability. One of its causes is a mutation in a single gene, ARX, which is found in inhibitory, ‘braking’ interneurons and is essential for their migration during early brain development. Without ARX, these cells fail to find their correct destinations. Dr. Noebels developed the first genetic mouse model of ISS that recapitulates major features of the human disorder. They have now discovered that early treatment with 17b-estradiol prevents the major clinical and cellular aspects of the disease. This estrogen is a naturally occurring brain hormone that normally protects brain cells and stimulates them to mature. They wish to obtain answers that will help put this therapy to a direct clinical test: When is the best stage to give the treatment, what is the best dose, and which patients will most benefit? They will also address the additional safety issues regarding estrogen supplementation in infancy to advance this promising new treatment to a pilot clinical trial.
Prevention of West Syndrome
Doug Nordli (Lurie Children’s Hospital)
Metabolomic Biomarker Discovery in Infantile Spasms
Manisha Patel (University of Colorado Denver)
Metabolomic approaches can identify metabolic signatures (biomarkers) that represent global biochemical changes in disease, predict responses to treatment or medication side effects. This project is focused on metabolomic identification of biomarkers of pathophysiology and/or treatment effects in animal models of IS. Dr. Patel proposes to use a systems biology approach to discovering unique metabolites (biochemicals) that may help them better understand the basis of IS and provide a signature in the blood and/or cerebrospinal fluid.
Infantile Spasms: Clinical and Genetic Predictors of Outcomes and Therapeutic Insights
Elliott Sherr (University of California San Francisco)
Dr. Elliott Sherr is a leading member of a multi-site consortium study investigating the largest ever assembled cohort of Epileptic Encephalopathy (EE) patients. Through the Epilepsy Phenome Genome Project (EPGP), a 27-site international consortium of epilepsy investigators, a repository of clinical and genetic information was created, providing the researchers with unprecedented clinical and genetic information of this cohort. In order to look at long-term outcomes of this already assembled group of patients, the CURE project aims to collect epidemiological data and biological samples to investigate predictors of epilepsy, neurodevelopmental outcomes, and neuropsychiatric comorbidities associated with epileptic encephalopathies. The data collected will be analyzed in conjunction with genetic information obtained through EPGP/EPi4K. Characterizing the phenotypic heterogeneity of specific gene defects associated with epileptic encephalopathies will have major implications for therapeutic choices, prognosis and genetic counseling for children and their families.
Infantile Spasms: Mechanisms and Consequences as Therapeutic Targets
John Swann (Baylor College of Medicine)
Dr. Swann's laboratory has developed an animal model which reproduces many of the distinguishing neurophysiological features of the human infantile spasms syndrome - including the ictal events that are concurrent with behavioral spasms and the highly abnormal interictal EEG pattern, hypsarrhythmia. Using a multidisciplinary approach, which includes continuous long-term video/EEG recordings, they are screening for novel therapies to stop spasms and hypsarrhythmia. The hypothesis is that an injury to the infant brain disrupts the normal activity-dependent growth of nerve cells & particularly inhibitory interneurons. Moreover, they think that treatment with growth factors that normally mediate interneuron growth will not only stop spasms and hypsarrhythmia but will also promote normal brain maturation and thereby alleviate some of the neurobehavioral comorbidities associated with this catastrophic epilepsy.
Developing and testing novel treatments for infantile spasms
Libor Velisek (New York Medical College)
Anne T. Berg, PhD
Howard Goodkin, MD, PhD
University of Virginia Medical Center
Henrik Klitgaard, PhD
Daniel Lowenstein, MD
University of California, San Francisco
Jong Rho, MD
University of Calgary
Annamaria Vezzani, PhD
Mario Negri Institute