CURE - Citizens United for Research in Epilepsy It's Time We Found a CURE CURE Epilepsy Research

Infantile spasms (IS) is a rare childhood epilepsy syndrome that can have profoundly negative long-term developmental and cognitive consequences.

Disease onset is typically between 3-7 months of age, and many children develop other seizure syndromes as they age. Infantile spasms is characterized by hypsarrhythmia on the EEG, a developmental feature unique to this syndrome. Importantly, a strong correlation has been noted between the presence of hypsarrhythmia plus spasms and cognitive and developmental delays.

Complete control of spasms can lead to an improved long-term outcome; however, currently available treatments are not always effective and are often associated with substantial adverse effects. As such, CURE has begun a directed grant program to accelerate the understanding of infantile spasms and advance a new, disease-modifying therapy into the clinic.

Since January 2013, CURE has awarded over $2 million to the following 8 investigators and their teams:

Advisory Panel

APC cKO mouse as a new model of infantile spasms
Chris Dulla (Tufts University)

GalanopoulouIdentifying 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.

NoebelsInfantile 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)

PatelMetabolomic 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.

SherrInfantile 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.

SwannInfantile 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
Northwestern University

Howard Goodkin, MD, PhD
University of Virginia Medical Center

Henrik Klitgaard, PhD
UCB Pharma

Daniel Lowenstein, MD
University of California, San Francisco

Jong Rho, MD
University of Calgary

Annamaria Vezzani, PhD
Mario Negri Institute

 

One of the goals for this initiative is for all funded laboratories to function as part of a collaborative team focused on a common goal: finding a cure for infantile spasms. We look forward to providing you with updates throughout the initiative.

 



 

 

 

CURE For questions, please contact Julie Milder at the CURE office, 312.255.1801, or email julie@cureepilepsy.org.

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