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Novel therapy for Fragile X syndrome

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41MH115529-01
Agency Tracking Number: R41MH115529
Amount: $834,798.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 101
Solicitation Number: PA16-302
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-09-15
Award End Date (Contract End Date): 2019-07-31
Small Business Information
San Diego, CA 92121-2734
United States
DUNS: 963248807
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (619) 917-0639
Business Contact
Phone: (858) 657-0918
Research Institution
9500 Gilman Drive, Mail Code 0934
LA JOLLA, CA 92093-0934
United States

 Nonprofit College or University

Fragile X syndromeFXSis the most common inheritable form of cognitive impairment and the leading known
genetic cause of autismFXS is caused by the loss of expression of the fragile X mental retardation proteinFMRPA major challenge for FXS research is to develop treatment strategies that improve the intellectual
capabilities of patientsDysregulated protein synthesis is widely accepted as a core molecular abnormality
associated with FXSBecause neuronal protein synthesis is critical for learning and memoryaltered synaptic
translation is considered a major contributor to the intellectual deficits seen in FXSCurrently available
pharmacological intervention strategies for FXS primarily treat behavioral problems and have focused largely
on targets upstream of translational control to normalize FXS related phenotypesWe have identified a specific
target that is a common downstream effector of both mTORCand ERK signaling and plays a direct role in
regulating translationGenetic deletion of the target in an animal model of FXS corrected exaggerated protein
synthesis and other biochemicalneuroanatomical and behavioral abnormalities associated with FXSThese
results suggest a strategy for developing a disease modifying therapeutic for FXSBy using a rational design
approach that combines structural protein information and optimal ADME propertieswe have discovered a
novel series of potent inhibitorsEpigen has developed specific and drug like small molecule inhibitors to this
targetas exemplified by lead compound EPGNWe have teamed up with DrAlysson Muotri s
laboratories at UCSD to propose a novel discovery paradigm for effective drug candidate compounds for FXS
by using newly developed cerebral organoidsormini brainsto model the disease inD in the laboratoryThe goal of this phaseSBIR work is to conduct focused lead optimization of our newly discovered series of
novel inhibitors as agents to treat FXSIn this worknew compounds will be identified utilizing our assay
cascade combining in vitro receptor pharmacologyADME assays and mouse pharmacokinetics to selectadvanced lead moleculeswhich will be evaluated in a human FXSmini brainThe best advanced lead
identified will be evaluated in a mouse model of FXS for biochemical and neuroanatomical outcomesThis
work will set the stage for detailed in vivo pharmacology assessment and IND enabling studies in the phaseSBIROur study will open up a new avenue of target specific drug development for Autism Spectrum Disorders
such as FXS

* Information listed above is at the time of submission. *

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