Inhibitors of STEP as a Novel Treatment of Fragile X Syndrome

Inhibitors of STEP as a Novel Treatment of Fragile X Syndrome

With a $349,000 grant from FRAXA Research Foundation from 2008-2015, Dr. Paul Lombroso and his team at Yale University researched if inhibiting STEP could reduce behavioral abnormalities in Fragile X syndrome. Results published.

Read more

NIH Awards $35 Million to Three Fragile X Research Teams

NIH Awards $35 Million to Three Fragile X Research Teams

The National Institutes of Health has just announced new awards of $35 million over five years to support three Centers for Collaborative Research in Fragile X. Investigators at these centers will seek to better understand Fragile X-associated disorders and work toward developing effective treatments. All of these scientists have been funded for years by FRAXA Research Foundation, and now each team will receive over $2 million per year for five years!

Read more

Cellular-Specific Therapeutic Targeting of Inhibitory Circuits in Fragile X Syndrome

Cellular-Specific Therapeutic Targeting of Inhibitory Circuits in Fragile X Syndrome

Studies have shown that the function of inhibitory networks is disturbed in Fragile X. This abnormality is not well understood but appears to be secondary to abnormalities in metabotropic glutamate and endocannabinoid systems. With a $90,000 grant from FRAXA in 2013-2014, Dr. Molly Huntsman’s team examined how these networks interact and how inhibitory deficits can best be remedied.

Read more

Seizures in Fragile X Syndrome and Therapeutic Potential of NMDA Receptor Antagonists

Seizures in Fragile X Syndrome and Therapeutic Potential of NMDA Receptor Antagonists

With a $90,000 grant from the FRAXA Research Foundation, Dr. Robert Wong is investigating how seizures are generated in Fragile X neurons. More generally, he is looking at how synapses are modified to enable learning and memory and how this process is impaired in Fragile X.

Read more

Potassium Channel Modulators to Treat Fragile X

Potassium Channel Modulators to Treat Fragile X

With $246,000 in funding from FRAXA over 2012-2014, the Yale University team of Leonard Kaczmarek, PhD, showed that loss of FMRP leads to an increased Kv3.1 potassium currents and decreased Slack potassium currents in neurons. Both of these changes impair timing of action potentials in auditory neurons (and likely others throughout the brain). The team also found that the firing pattern of neurons in response to repeated stimulation is severely abnormal in Fragile X mice. Based on these results, they are collaborating with the UK-based company Autifony to develop and test advanced compounds which may reverse these deficits.

Read more

Preclinical Evaluation of Serotonin Receptor Agonists as Novel Pharmacological Tools in Fragile X Syndrome

Preclinical Evaluation of Serotonin Receptor Agonists as Novel Pharmacological Tools in Fragile X Syndrome

With a $66,000 grant from FRAXA Research Foundation in 2013, Dr. Lucia Ciranna and her team from the Universita di Catania tested if specific serotonins could reverse abnormal phentotypes found in Fragile X syndrome. 

Read more

The Endocannabinoid System in a Mouse Model of Fragile X Syndrome

The Endocannabinoid System in a Mouse Model of Fragile X Syndrome

With a $128,500 grant over 2011-2013 from FRAXA Research Foundation, Drs. Bradley Alger and Ai-Hui Tang at the University of Maryland researched endocannabinoid pathways in Fragile X.

Read more

Ab-Mediated Translation in Fragile X Syndrome

Ab-Mediated Translation in Fragile X Syndrome

With a $120,000 grant from FRAXA Research Foundation during 2011-2012, Dr. Cara Westmark at the University of Wisconsin explored the role of AbPP as a potential treatment option for fragile X. AbPP produces b-amyloid which is over-expressed in Alzheimer’s disease (AD) and Down syndrome. 

Read more

Inherited Channelopathies in Cortical Circuits of Fmr1 KO Mice

Inherited Channelopathies in Cortical Circuits of Fmr1 KO Mice

With this two year award of $90,000, Dr. Zhang and Principal Investigator Dr. Andreas Frick at Neurocentre Magendie in France investigated channelopathies using Fragile X mice. Many other proteins are misregulated as a result of the absence of FMRP. It is known that many ion channels, the pores in the cell membrane which allow neurons to conduct electrical impulses, have altered levels in Fragile X. This state is sometime called a “channelopathy” in the pharma world. This group is studying the effect of specific alterations in ion channels, and potential therapeutic effects of drugs which open and close these channels.

Read more

Using Fenobam to Reduce APP and Abeta in Fragile X Mice

Using Fenobam to Reduce APP and Abeta in Fragile X Mice

With a $130,000 grant from FRAXA Research Foundation over 2008-2009, Drs. James Malter and Cara Westmark at the University of Wisconsin studied the relationship between the Fragile X protein FMRP and APP, a protein important to the pathology of Alzheimer’s Disease. APP may also contribute to the pathology of Fragile X, and its major metabolite, Aß, may contribute to abnormal protein synthesis via a positive feedback loop. This project sought to restore normal dendritic protein synthesis in Fragile X mice by breaking into this loop.

Read more

Taurine and Somatostatin as Potential Treatments for Fragile X Syndrome: A Unifying Neuro-Endocrine Hypothesis

With a $74,000 grant from FRAXA Research Foundation, Dr. Abdeslem El Idrissi at CUNY explored the GABA receptor system in Fragile X mice and tested somatostatin and taurine as potential therapies for Fragile X; while somatostatin must be infused intravenously, taurine is available as a nutritional supplement.

Read more

Decreased Excitatory Drive onto Parvalbumin-Positive Neocortical Inhibitory Neurons in a Mouse Model of Fragile X Syndrome

Decreased Excitatory Drive onto Parvalbumin-Positive Neocortical Inhibitory Neurons in a Mouse Model of Fragile X Syndrome

With an $80,000 grant from FRAXA Research Foundation over 2006-7, Drs. Jay Gibson and Kimberly Huber at the University of Texas at Southwestern examined if the defected inhibitory neurotransmission was a primary or secondary symptom of Fragile X to determine where future treatment targets should be focused.

Read more

Electrophysiological, Biochemical and Immunohistochemical Characterization of Kv3.1 in Auditory Brainstem Nuclei in the Fragile X Knockout Mouse

Electrophysiological, Biochemical and Immunohistochemical Characterization of Kv3.1 in Auditory Brainstem Nuclei in the Fragile X Knockout Mouse

With $80,000 in funding from FRAXA over several years, the Yale University team of Leonard Kaczmarek, PhD showed that loss of FMRP leads to an increased Kv3.1 potassium currents. This change impairs timing of action potentials in auditory neurons (and likely others throughout the brain).

Read more

Baclofen: GABA(B) Receptor Supersensitivity and Normalization of Behavioral Abnormalities by Various GABA(B) Agonists Including Baclofen in FMRP Deficient Mice

Baclofen: GABA(B) Receptor Supersensitivity and Normalization of Behavioral Abnormalities by Various GABA(B) Agonists Including Baclofen in FMRP Deficient Mice

With $110,000 in grants from FRAXA Research Foundation over several years, Dr. Miklos Toth from Cornell University discovered increased startle response in Fragile X mice and that baclofen can correct this phenotype.

Read more

Therapeutic Interventions in FMR1 Knockout and Transgenic Mice: Role of the FMR1 Gene

Therapeutic Interventions in FMR1 Knockout and Transgenic Mice: Role of the FMR1 Gene

With a $229,000 grant from FRAXA Research Foundation in 2006, Drs. Richard Paylor, David Albeck, and Francis Brennan at the Baylor College of Medicine found that, in mice as in humans, the level of Fragile X protein in brain cells plays a prominent role in determining levels of activity and anxiety.

Read more

Transgenic Mouse Models of Fragile X Syndrome

Transgenic Mouse Models of Fragile X Syndrome

With $736,000 in grants from FRAXA Research Foundation over 2000-2007, Dr. Robert Bauchwitz at Columbia University developed 15 transgenic mouse models of Fragile X syndrome, using them to evaluate a range of experimental treatments. Results published.

Read more

Role of Experience in Regulating Levels of the Fragile X Protein

Role of Experience in Regulating Levels of the Fragile X Protein

FRAXA awarded $29,000 in 2001 and $20,000 in 2000 to Kenneth J. Mack, MD, PhD — Mayo Clinic with Peter K. Todd, MD, PhD, Postdoctoral Fellow. While a professor at University of Wisconsin-Madison, Dr. Mack investigated whether and how FMRP levels are regulated in response to neuronal stimulation in vivo (in live animals). He looked at the effects of seizures and of experience in his experiments. Dr. Mack and colleagues published their findings.

Read more

Molecular Basis of Increased Seizure Severity in the Fragile X Knockout Mouse

With a $50,000 grant from FRAXA Research Foundation from 2002-2003, Dr. Carl Dobkin and his team at the New York Institute for Basic Research studied the causes for heightened seizure activity in Fragile X mice. Results published.

Read more

Treatment of a Mouse Model of Fragile X Syndrome with MPEP

Treatment of a Mouse Model of Fragile X Syndrome with MPEP

With a $49,000 grant from FRAXA Research Foundation in 2003, Dr. Linda Crnic at the University of Colorado continued studies of MPEP in Fragile X mice, exploring whether chronic use improves symptoms of Fragile X syndrome without impairing cognitive function.

Read more