Evaluation of the rASO in the Rat Model of Angelman syndrome | $149,908

The objective of this grant is to evaluate the behavioral rescue in a rat model of AS after treatment with a rat specific ASO designed by Dr. Dindot’s lab. FAST’s unique rat model provides the opportunity to investigate more complex behaviors that have been difficult to capture in mice, which include developmental milestones, neonatal calling […]

Evaluation of IGF-2 in a Rat Model of Angelman syndrome | $165,000

The overall objective of the proposal is to evaluate whether insulin-like growth factor-2 (IGF-2) or an IGF-2 receptor ligand L1 (L1) as a potential therapeutic for Angelman syndrome (AS). The principal investigator (PI) proposes to test IGF-2 and L1 on novel phenotypes recently identified in a novel AS rat model. The PI proposes three specific […]

ATFs 2.0: UBE3A Activation without SNORD Inhibition | $103,235

Dr. Segal’s past work on Artificial transcription factors (ATFs) showed global paternal gene activation after subcutaneous injection. In bringing this therapeutic platform to the next level for human use it was prudent to evaluate options to find a mechanism of ensuring that we do not inhibit the SNORD116 and SNORD115 RNAs, which are associated with […]

Evaluation of rASO in a Rat Model of Angelman syndrome | $165,000

The use of ASOs to interrupt the paternal UBE3a allele silencing through antisense inhibition is a potential therapeutic approach for treating AS in humans. Here 3 University teams (USF, UC Davis and BCM) collaboratively propose to determine optimal sequence and concentration range for rat ASOs for the rat homologue. This study will allow the determination […]

Pilot Feasibility of an Enzyme Replacement Therapy for Angelman syndrome | $75,000

A non-permanent treatment for genetic disorders that result in a missing enzyme has been the focus for many disorders over the last few decades through enzyme replacement therapy (ERT). These types of drugs have been approved by the FDA for various conditions (Pompe disease, MPS, Gaucher’s disease, etc). Angelman syndrome is a disorder that results […]

Translational Research in a Pig Model of Angelman syndrome | $1,111,112

Dr. Scott Dindot is using an AS pig model to develop, test, and validate potential AS therapeutics and to characterize the AS pig. This testing gets us another step closer to robust preclinical phase testing of potential therapeutics for Angelman syndrome and evaluation of novel behavior changes seen in this large animal model.

Evaluation of Safety and Tolerability of a Nutritional Formulation in AS.

Lowering carbohydrate content of the diet and increasing the fat content (through either a ketogenic diet, MCT based diet, modified Atkins diet, or the low glycemic index diet [LGIT]) has been shown to effectively decrease seizure frequency in patients with epilepsy and AS. Specialized medical food formations have been developed to transition patients to low […]

Evaluation of ERP

This project will capitalize on the pilot grant that was funded in 2017 showing that brief, noninvasive, low-cost brain-based measures of learning in children and adults with deletion subtype of AS can complement and extend informant reports of adaptive functioning. Without the need for voluntary behavioral response, these measures are optimal across ages and levels […]