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Evaluating the Efficacy of Targeted Deep Brain Stimulation (DBS) in Attenuating Refractory Infantile Epilepsy Spasm Syndrome (IESS) in a Rodent Model

Award Number: R03NS148675
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Evaluating the Efficacy of Targeted Deep Brain Stimulation (DBS) in Attenuating Refractory Infantile Epilepsy Spasm Syndrome (IESS) in a Rodent Model - Infantile Epileptic Spasms Syndrome (IESS) is a devastating early-onset epilepsy syndrome characterized by spasms and interictal hypsarrhythmia on EEG occurring during infancy. Current treatments, including ACTH and vigabatrin, frequently fail and carry serious side effects such as immune suppression and vision loss. There is a pressing need for safer, more effective therapies, particularly for drug-resistant cases. This proposal explores deep brain stimulation (DBS) targeting specific hypothalamic nuclei as a novel strategy to suppress seizures and normalize EEG in IESS. Our central hypothesis is that frequency-specific DBS of the paraventricular hypothalamic nucleus (PVH) and arcuate nucleus (Arc) will modulate pathological network excitability, suppress spasms and hypsarrhythmia, and prevent subsequent spontaneous seizures. Preliminary microinfusion data strongly support a central role for the PVH-Arc network in regulation of spasms. DBS targeting of this circuitry offers a mechanistically guided, neuromodulatory strategy that may overcome limitations of current therapies. Using a validated rat model that recapitulates both the clinical and electrographic features of IESS (via prenatal betamethasone exposure followed by postnatal NMDA-induced spasms) we will test the following aims: Aim 1: Evaluate proof-of-principle therapeutic efficacy of DBS in PVH or Arc using high- frequency (HF) stimulation in Arc and low-frequency (LF) stimulation in PVH, mimicking inhibitory and excitatory neuromodulation, respectively. Aim 2: Optimize DBS stimulation paradigms by (a) assessing how LF vs HF stimulation of each target modulates seizures and EEG features, and (b) evaluating the effects of concurrent stimulation in both PVH and Arc. Key outcome measures include spasm frequency and latency, EEG quantification of hypsarrhythmia and electro-decrement, and assessment of spontaneous seizures later in development. Data will be benchmarked against pharmacologic interventions including ACTH and ANAVEX®2-73 [blarcamesine]. By leveraging techniques in developmental EEG monitoring and DBS in a rigorously validated animal model, this study has the potential to transform therapeutic approaches for IESS and open new avenues for treating drug-resistant pediatric epilepsies.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $162,400 )
2026	2026	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/4/2026	NEW	$162,400
														Subtotal = $162,400

Grand Total All Awards = $162,400

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Evaluating the Efficacy of Targeted Deep Brain Stimulation (DBS) in Attenuating Refractory Infantile Epilepsy Spasm Syndrome (IESS) in a Rodent Model

Award Number: R03NS148675

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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