Fragile X disrupts endocannabinoid signaling. This study in mice demonstrated that correcting it may calm brain hyperexcitability and improve symptoms.
STEP inhibition reversed behavioral and synaptic Fragile X deficits in mice (Neuropharmacology, 2018), highlighting STEP as a promising treatment target.
With FRAXA funding, Dr. Jaffrey linked FMR1 loss to abnormal dendritic spines via RhoA signaling, suggesting RhoA-targeted therapies could help treat Fragile X.
There is no effective treatment for the rare genetic disorder Fragile X syndrome, so two parents created a foundation to fund research. But they found there’s no easy road to a cure. For a few weeks last year, Michael Tranfaglia and Katie Clapp saw a remarkable change in their son, Andy…
This isn’t a Fragile X trial, but the Neuren compound, NNZ-2566, that is in trials now for Fragile X has shown significant positive effects in a Phase 2 trial for Rett syndrome.
CB1 blockade with rimonabant reversed cognitive, sensory, and seizure symptoms in FXS mice, highlighting the endocannabinoid system as a therapeutic target.
Ion channel defects (“channelopathies”) in Fragile X disrupt neuron firing and network balance. This study maps these channel changes to guide targeted treatments.
An early trial of green tea extract EGCG improved cognition in Fragile X. It targets ERβ and reduces overactive PI3K/mTOR/ERK signaling linked to FXS symptoms.
FRAXA-funded work showed CDK5 signaling is disrupted in Fragile X. CDK5 drugs are in development for Alzheimer’s so this pathway offers a promising new FX treatment angle.
FRAXA-funded researchers used advanced computer models to uncover how FXS brain circuits change and predict which treatments may correct them. Results published.
Stanford scientists used human stem-cell–derived neurons to show that retinoic acid signaling is blocked by Fragile X, revealing a new pathway to target for treatment.
Fragile X neurons show leaky mitochondria and excess Bcl-xL–driven synapses. Targeting this pathway may restore energy balance and healthier brain development.
Dr. Wong studies how NMDA and mGluR receptors interact to trigger seizures in Fragile X, revealing NR2B-specific blockers as a promising targeted treatment.
by Michael Tranfaglia, MD. In my opinion, the Fragile X clinical trials of AFQ056 sponsored by Novartis failed because of a dose range that was inadequate for Fragile X, and because of the unexpected development of tolerance.
This paper shows that MMP-9 dysregulation is a critical part of the pathology of Fragile X, and MMP-9 should be considered a major treatment target for Fragile X syndrome.
This year’s Gordon Conference just finished, and Novartis presented their results. To say that the trial results for AFQ056 were disappointing would be the understatement of the century!
