Recherche
Current Projets
I centri di ricerca in tutto il mondo lo sonoiniziando progetti per comprendere meglio l'aspetto specifico del gene FOXP1 e come funzionagenetico le mutazioni influiscono su questicon sindrome FOXP1. La ricerca necessita della partecipazione dei genitori dei bambini affetti dalla sindrome per contribuire con i resoconti genetici, l'anamnesi medica e le tappe fondamentali dello sviluppo dei loro figli. Con il contributo di molte famiglie FOXP1, i ricercatori saranno in grado di analizzare i dati e pubblicare i loro risultati con l'obiettivo identificando tratti e caratteristiche unici del nostro chibambini.
Attualmente sono in corso i seguenti progetti di ricerca. Chiedono il tuo supporto e il tuo contributo di informazioni. Molti dei progetti cercano volpi più anziane, per costruire la loro base di conoscenze. La Fondazione internazionale FOXP1 ha sostenuto questi progetti.
Se desideri che la comunità FOXP1 to partecipare nel tuo studio di ricerca, completa il modulo "Modulo Richiesta di Partecipazione" trovatoQui.
~ La ricerca è il modo in cui noicostruire la conoscenza di FOXP1Sindrome ~
Joseph Buxbaum, Seaver Autism Institute, Mt. Sinai Hospital
Three-dimensional Organoid Model of FOXP1 Syndrome ($50,000)
The ultimate goal of this project is to develop an in vitro medium-to-high throughput
assay for screening of compound libraries. The “hits” from such a screen will be defined as compounds that “normalize” the FOXP1 organoid phenotype in a dose-dependent manner. While there is no obvious mechanistic or functional link between the organoid phenotype and the clinical presentations, it is reasonable to assume that changes in organoid development reflect changes in brain development and that utilizing organoid phenotypes validated in patient-derived cell lines carrying clinically-relevant mutations will ensure identification of potential drug candidates. This approach is in line with the current industry standards for development of the high-throughput screening assays. These drug candidates (hits) will be further validated in a number of n vitro and in vivo assays to validate preclinical efficacy and provide more mechanistic insight.
Genevieve Konopka and Jay Gibson
Functional restoration of FOXP1 haploinsufficiency using AAV-mediated gene rescue in the brain ($73,274)
Understanding FOXP1 function in the mouse brain is crucial to develop effective
therapeutics for FOXP1 syndrome in humans. In this project, we will use a mouse
model that mimics the genetic basis of many forms of FOXP1 syndrome, where only
one out of the two functional copies of FOXP1 gene is present. We will perform
intracerebroventricular (ICV) injections of a unique adeno associated virus (AAV)
called AAV9 and/or its modified and improvised version (AAV-PHP.eB) at an early
developmental stage to restore FOXP1 expression in the brains of these mice. In this
strategy, FOXP1 will be re-expressed under the control of the human synapsin 1 promoter, ensuring neuron specific expression. We will then examine whether FOXP1
gene replacement can correct behavioral deficits in the mice. If successful, we will
extend the gene restoration to later developmental time points to determine a
potential critical window of gene replacement therapy in this mouse model. Results
from this project should provide fundamental knowledge about the feasibility of FOXP1 gene therapy in humans and form the basis for future clinical trials.