Fragile X Cure One Step Closer with FRAXA Support of $1 Million in New Research
2016: 4 Countries - 10 Teams - $1 Millions
From finding new treatment targets, to pinpointing outcome measures for future clinical trials, to attempting to reactivate the gene which is silenced in Fragile X syndrome, these innovative scientists will bring us closer to a cure.
Improving Clinical Trials
Many parents of children with Fragile X know well the struggles of getting their children to sleep through the night. Mice and fruit flies engineered to mimic Fragile X Syndrome also have disrupted sleep. Drs. Westmark and Smith will test potential therapeutics in mice using sleep as an outcome measure and investigate whether sleep could be used as an outcome measure for future clinical trials.
The search is on for a simple blood test to measure how well a treatment works for an individual with Fragile X. Dr. Frank Kooy’s team investigates.
Testing Treatment Targets
One of the goals of FRAXA’s research program has been to find biological pathways affected in Fragile X that are amenable to treatment with small molecules (drugs). Past efforts have been successful, generating large numbers of treatment targets, and this year, Dr. Osterweil and Dr. Bardoni will study new promising targets.
All these treatment targets raise an important question: are these various neural pathways and targets related at some key point? Is there a critical node, a point where pathways connect, which would allow for the most effective treatment? Two projects funded last year are looking for just such critical nodes (see Vanderklish and Moine). Until a critical node is found, we may need combinations of drugs to best help people with Fragile X syndrome. Dr. Razak’s study of combination treatments aims to show us the best way forward and form the basis for success in clinical trials.
Reactivating the Fragile X Gene
The holy grail of Fragile X research is to reactivate the gene, FMR1, which is silenced in people who have the syndrome. Using genetic engineering, researchers can already switch on the gene in adult Fragile X mice, and correct symptoms in this way. Teams led by Dr. Peter Todd and Dr. Jeannie Lee will pursue gene reactivation in mice using the new technique, CRISPR.
Congratulations to the new grantees! The grand total of these awards is $1,022,000 over the next two years. Additional awards still to come!
Effects of Metformin in Fmr1 Knockout Mouse Model of Fragile X Syndrome
Metformin, a safe diabetes drug, activates AMPK to rebalance protein synthesis. FRAXA-funded work investigated its potential to treat Fragile X.
Combinatorial Drug Treatment in a Model of Fragile X Syndrome using Novel Biomarkers
University of California researchers Khaleel Razak, PhD, and Jonathan W. Lovelace, PhD, explored drug combinations to limit hypersensitivity to sounds in Fragile X mice.
Targeted Transcriptional Reactivation of FMR1 in Fragile X Syndrome Stem Cells
FRAXA funded Dr. Peter Todd to use CRISPR to reactivate FMR1. Published results confirmed restored gene expression, a big step toward disease-modifying therapy.
Investigating Gene Reactivation to Treat Fragile X Syndrome
With a $180,000 grant from FRAXA Research Foundation, Dr. Jeannie Lee and her team at Harvard are working to reactivate the gene that is silenced in Fragile X syndrome.
Mechanisms of Tolerance to Chronic mGluR5 Inhibition
FRAXA supported research showing mGluR5 antagonist tolerance develops quickly in Fragile X models, guiding new strategies to prevent or overcome it.
Prefrontal Cortex Network (PFC) Dynamics in Fragile X Syndrome
The team has shown that Fragile X mice have major prefrontal cortex deficits in Fragile X mice. Finding ways to overcome this could reveal new intervention strategies.
Correcting Defects in Astrocyte Signaling in Fragile X Syndrome
Astrocytes, brain cells which support neurons, do not transmit signals. Fragile X treatment strategies have been proposed based on correction of “astrocyte phenotypes”.
Altered Neural Excitability and Chronic Anxiety in a Mouse Model of Fragile X
With a $35,000 grant from FRAXA, Dr. Peter Vanderklish at Scripps Research Institute, and colleagues, explored the basis of anxiety in Fragile X syndrome.
Preclinical Testing of Sleep-Wake Patterns as an Outcome Measure for Fragile X
FRAXA Research Foundation awarded $122,000 to Dr. Cara Westmark at the University of Wisconsin at Madison for studies of sleep disorders in Fragile X syndrome.