5 Research Projects Win Funding From Dravet Syndrome Foundation
US nonprofit awards $690K for projects to improve patient care
The Dravet Syndrome Foundation (DSF) has announced the award of $690,000 in total research funding for five projects that aim to improve care for people with Dravet syndrome.
The one- to two-year research grants will provide each project funding in amounts ranging from $75,000 to $165,000. Two of the projects are being co-funded by JAM for Dravet, a nonprofit founded by the parents of a young boy with Dravet syndrome.
The goals of these projects range from finding markers to help reduce the risk of sudden unexpected death in epilepsy (SUDEP), a rare complication of seizures, to studying the potential use of odor therapy, called aromatherapy, to control seizures.
“DSF is proud to be the largest non-governmental funder of Dravet syndrome research worldwide, and is pleased to work with JAM for Dravet to increase our impact,” Mary Anne Meskis, executive director of the nonprofit, said in a foundation press release.
Veronica Hood, PhD, the DSF’s scientific director, said the foundation is “funding strong scientists with projects that are aligned with community priorities that include a focus on genetic therapies, alternative treatment approaches, comorbidities, and [sudden death].”
3 projects focus on SUDEP
A two-year project entitled “Genetic Substrates and Physiological Triggers for Autonomic and Cardiac Abnormalities in Dravet Syndrome” was awarded $150,000, co-funded by JAM. Led by David Auerbach, PhD, an assistant professor of pharmacology at the State University of New York (SUNY) Upstate Medical University, it focuses on SUDEP.
People with Dravet syndrome have a 15 times higher risk of SUDEP than those with other types of childhood-onset epilepsy. While controlling seizures can decrease the risk of sudden death in these patients, clinicians have found that Dravet-associated seizures are often resistant to anti-seizure medication.
As such, identifying potential early markers of SUDEP in Dravet patients may help predict and prevent this severe and life-threatening complication.
Auerbach’s previous research in cell and animal models suggested that Dravet-causing mutations lead to electrical problems in the heart, and that abnormal heart rhythms (arrhythmias) preceded SUDEP.
In the new project, researchers will perform detailed analyses of the heart’s electrical function in people with Dravet and another severe form of epilepsy both in non-seizure states and before and after seizures. The results are expected to help develop markers that can predict the risk of heart-mediated SUDEP so that early interventions can be given.
Another project, led by Ashwini Sri Hari, PhD, of the University of Utah, is titled “Evaluating the effects of sub-chronic exposure to sub-clinical levels of CO on Dravet etiology and associated SUDEP risk.”
This one-year study, awarded $75,000, aims to assess whether and how exposure to carbon monoxide (CO) — a toxic air pollutant linked to an increased risk of epilepsy hospitalizations and sub-clinical seizures — worsens disease mechanisms in Dravet patients. Researchers also will investigate potential connections between CO exposure and risk of SUDEP.
A third project, “Effect of odorant on mortality and extended amygdala activation in Dravet syndrome,” is co-funded by JAM for Dravet and led by William Nobis, MD, PhD, an assistant professor at Vanderbilt University. It is receiving the largest award, of $165,000.
The parts of the brain that process the sense of smell are directly connected to the extended amygdala — a group of brain regions that are important for responding to stress, and have recently been implicated in seizure activity.
Evidence suggests that smelling specific odors could modulate activity in these brain regions to help reduce seizures. Now, Nobis and colleagues will build on preliminary data suggesting that chronic exposure to 2-phenylethanol, which provides a “rose odor,” significantly reduces mortality in a mouse model of Dravet.
The team aims to better explore the effects of 2-phenylethanol exposure on mortality, seizure frequency, and neuropsychiatric conditions in this model.
“This work would provide scientific rationale for the use of odor therapy to manage symptoms of epilepsy and [Dravet syndrome],” the researchers wrote in the project’s summary.
“This would be immediately clinically impactful and could readily be evaluated in clinical setting to prove efficacy in human patients,” they added.
A focus on patient care
Led by Gaia Colasante, PhD, of Vita-Salute San Raffaele University, in Italy, another project focuses on gene mutations in Dravet. Titled “Reactivating Scn1a gene in different interneuron subtypes to dissect their contribution to Dravet syndrome phenotype,” this two-year research study received funding of $150,,000.
Nearly all cases of Dravet syndrome are caused by mutations in the SCN1A gene, which provides instructions for making a subunit of the sodium channel protein NaV1.1 that’s important for nerve cell activity.
Colasante and colleagues will assess how restoring NaV1.1 levels in different subtypes of brain cells affects the main aspects of Dravet, including seizures, SUDEP, and behavioral problems. To do so, they will use a newly developed mouse model that allows the researchers to modulate how much of this protein is produced in different brain cells.
One of their goals is to identify which cell type(s) would be most important to target in gene therapy strategies for Dravet. Such strategies aim to restore NAV1.1 production.
Finally, a project headed by Mackenzie Howard, PhD, a research assistant professor at the University of Texas at Austin, is titled “Cerebellar deficits as mechanisms for motor, cognitive, and social dysfunction in Dravet syndrome.” It was awarded research funding of $150,000 over two years.
Many Dravet patients experience difficulties with coordination, learning, and memory, even when seizures are well-controlled with medication.
Howard’s prior research in a mouse model of Dravet showed that certain nerve cells in the cerebellum, a part of the brain involved in movement, cognition/memory, and social behavior, showed abnormally reduced activity.
In the awarded project, researchers will use a new mouse model in which Dravet-causing mutations are present only in these specific cerebellar cells. This way, they will be able to assess whether and how functional changes in these cells and the overall cerebellum lead to motor, social, and learning difficulties.
The 2022 project grants bring the total DSF research funding to date, since 2009, to nearly $6.4 million, according to the foundation.
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