Why are some with Fragile X always hungry or overweight, yet rarely diabetic? This team is studying metabolism and testing treatments like metformin and diet.
We have long suspected that the clinical trials of mGluR5 blockers from Novartis and Roche failed because the drug triggered tolerance, losing effect over time. With a $90,000 grant from FRAXA, Dr. Patrick McCamphill, a Postdoctoral Fellow in the MIT lab of Dr. Mark Bear, is investigating. He does indeed find tolerance, and now he is looking for ways to overcome it.
FRAXA Investigator and MIT Professor Mark Bear and his colleagues have identified a valuable new target for Fragile X therapeutics: GSK3 alpha. Several FRAXA research teams previously identified GSK3 beta as a treatment target for Fragile X. The catch is that, so far, GSK3 beta inhibitors have proven too toxic for regular use. Dr. Bear’s new discovery opens up the possibility of developing more selective compounds with less toxicity and fewer side effects. Interestingly, lithium inhibits both GSK3 versions – alpha and beta.
FRAXA funded MIT work to probe tolerance to key Fragile X drugs, including mGluR5 inhibitors and arbaclofen, and to identify ways to sustain long-term treatment benefits.
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.
FRAXA has focused on identifying existing, approved drugs that could be repurposed for Fragile X, allowing potential treatments to move faster and at lower risk than starting from scratch. We’ve worked to advance the most promising candidates toward real-world use.
With this grant from FRAXA, Dr. Peter Vanderklish explored AMPK activators to treat Fragile X. Both metformin and resveratrol, found in red wine, are AMPK activators.
A bizarre marine critter found off the California coast — Bugula neritina— is the only known source of a potential new Fragile X treatment, Bryostatin. Last month, FRAXA sat down with scientists from Neurotrope BioScience, a specialty biopharmaceutical company developing medicines for rare diseases and Alzheimer’s based on Bryostatin. Their Fragile X program is based on research by a West Virginia team led by Daniel Alkon, MD, which showed that Bryostatin-1 restores hippocampal synapses and spatial learning and memory in adult Fragile X mice.
Dr. Jope found that lithium (at usual therapeutic doses) and investigational GSK3 inhibitors can reverse a number of cognitive deficits in FMR1 knockout mice.
Early on, no one knew which path would work. Now the results are clear, and they’re directing FRAXA toward the next major Fragile X treatment breakthrough.
With a $219,500 FRAXA grant, Dr. Stephen Haggarty at Harvard/MIT used patient-derived stem cells to screen drugs targeting GSK3, aiming to enhance lithium therapy.
