Cure LGS 365 Research Grant Recipients

The LGS Foundation is dedicated to funding the highest caliber research on LGS

Our focus is on research projects that will help us end the devastation and suffering caused by LGS.

The LGS Foundation accepts unsolicited proposals year-round to seed new LGS research projects. Learn more about our Cure LGS 365 Grants Here.

 


2022 Research Grant Awardees

Ivan Soltesz, PhD & Ryan Jamiolkowski, MD, PhD

Stanford University

Preclinical Optimization of a Non-Invasive Approach to Deep Brain Stimulation in LGS

Project Summary:

Using low-intensity ultrasound, we can modulate brain activity in select areas, including deep in the brain like the thalamus, but more research is needed to understand how to harness this technology for seizure control. We have already demonstrated in mice that ultrasound can control cells in the same part of the thalamus (the centromedian nucleus) that deep brain stimulation targets in LGS patients. We have also shown that ultrasound aimed at a different brain target (the hippocampus) can stop seizures for temporal lobe epilepsy, a different kind of epilepsy from LGS. In this project, we will combine those findings to target the centromedian thalamus in mice that have seizures from LGS. If that intervention succeeds, then focused ultrasound could be a non-invasive substitute for deep brain stimulation in LGS, circumventing the need for surgery.


Previous LGS Foundation Funded Research Grants

Dr. Linda Dalic

University of Melbourne, Australia Neurologist/Epileptologist
 

Optimizing Stimulation Parameters for Lennox-Gastaut Syndrome Neuromodulation (OPTISTIM+)

Project Summary: We are early in the journey of understanding epilepsy neuromodulation. Several class 1 studies have shown that epilepsy neuromodulation works, and we are now in the phase of unpacking which targets are most effective for which epilepsy syndromes, and which stimulation parameters are most effective. Parkinson’s Deep Brain Stimulation (DBS) was in a similar position 20 years ago, with evidence of therapeutic effect but a precise role not clearly defined. Following carefully conducted studies, exploring the role of different targets and stimulation parameters, DBS has now evolved to be a major plank of Parkinson’s therapy. We see the OPTISTIM+ study as an early and important part of a similar journey that seeks to develop epilepsy neuromodulation into a major therapeutic plank for Lennox-Gastaut Syndrome.

Dr. Jennifer Kearney, Ph.D.

Northwestern University Feinberg School of Medicine

RNA Modulation in KCNB1 Model of LGS
Lennox-Gastaut Syndrome (LGS) is a severe pediatric epilepsy syndrome that includes a characteristic EEG pattern, some degree of cognitive impairment, and multiple seizure types that respond poorly to available treatments. New therapies are needed to both better control seizures and improve other issues seen in LGS. Up to 35% of LGS cases have no obvious cause and are presumed to result from a genetic mutation. Heterozygous mutations in KCNB1 have been identified as a genetic cause in some patients with LGS. In genetic disease resulting from a heterozygous mutation, the individual has one good copy and one bad copy of the gene. A major unanswered question for KCNB1-associated LGS is whether the LGS results because one good copy is not enough, or from harmful effects of the bad copy of the gene. Based on our current understanding, we think that the bad copy exerts harmful effects and poisons the good copy. To formally investigate this, we will use a mouse model with a Kcnb1-associated LGS mutation and evaluate the effects of turning off the bad copy using a tool called antisense oligonucleotide (ASO). If we see improvement in neurological and behavioral symptoms in Kcnb1 LGS mice, it will provide evidence that harmful effects of the bad copy are responsible for the seizures and LGS. Addressing this critical gap in our knowledge will improve our understanding of LGS and pave the way for the development of an RNA-based disease-modifying therapy.

Colleen Carpenter, Ph.D.

University of California, San Francisco

Dissecting the interplay between genetic and metabolic deficits in LGS using Zebrafish
Dr. Carpenter and her team are pioneering the method of large-scale drug screening in zebrafish models of genetic forms of epilepsy. With these fish, the team is studying a number of genes that cause seizures that can lead to LGS and is testing treatments that can stop those seizures and the associated abnormal brain waves. It is believed that early treatment of genetic forms of epilepsy can prevent the evolution of seizures into LGS.

Daniel Shrey, M.D.,  Beth Lopour, M.D. and Mary Zupanc, M.D.

Children’s Hospital of Orange County

The effects of Felbamate on the evolution of LGS
Drs. Shrey, Zupanc. and Lopour are studying how LGS evolves. It is believed that the abnormal EEG patterns seen in LGS (e.g. slow spike and wave (SSW), paroxysmal fast activity (PFA)) are the cause of the disrupted brain development and developmental delay seen in most with LGS. This project looks at the evolution of LGS from pre-LGS to LGS plus SSW and PFA. It also tests whether or not the powerful drug felbamate can stop the evolution to LGS over time.

Zin-Juan Klaft, Ph.D.

Tufts University

GluN2D – dependent maturation of cortical interneurons and epilepsy – co-funded with the American Epilepsy Society

Kay-Marie Lamar, Ph.D.

Northwestern University

Defining the Molecular Mechanisms of CHD2 in LGS

Vanesa Nieto-Estevez, Ph.D.

UT Southwestern Medical Center

Modeling Lennox-Gastaut Syndrome in Human Cerebral Organoids

Aaron Warren, Ph.D.

University of Melbourne, Australia

Identifying neuroimaging predictors of treatment outcomes following deep brain stimulation in patients with Lennox-Gastaut syndrome

Nicholas Poolos, M.D., Ph.D.

University of Washington

Large scale analysis of antiepileptic drug efficacy in Lennox-Gastaut Syndrome

Robert Hunt, Ph.D.

University of California Irvine

CHD2 model for LGS

Candice Myers, Ph.D.

University of Washington

Identifying Genetic Causes of LGS

Brian Grone, Ph.D.

University of California, San Francisco

A Zebrafish Model for LGS

Elizabeth Thiele, MD, Ph.D.

Massachusetts General Hospital

Low Glycemic Index Treatment in Patients with LGS

Updated 11/30/2022