With a $90,000 grant from FRAXA Research Foundation, Dr. Patrick McCamphill and Dr. Mark Bear at Massachusetts Institute of Technology (MIT) will further investigate drug tolerance and ways to overcome it.
FRAXA Research Foundation was founded in 1994 to fund biomedical research aimed at finding a cure for Fragile X syndrome and, ultimately, autism. We prioritize translational research with the potential to lead to improved treatments for Fragile X in the near term. Our early efforts involved supporting a great deal of basic neuroscience to understand the cause of Fragile X. By 1996, these efforts had already begun to yield results useful for drug repurposing. To date, FRAXA has funded well over $25 million in research, with over $3 million of that for repurposing existing drugs for Fragile X. Here are some examples of FRAXA-funded work on repurposing available drugs for Fragile X syndrome: Lithium In the mid-1990s, the Greenough lab at the University of Illinois discovered that FMRP, the protein missing in Fragile X, is rapidly translated in dendrites in response to stimulation of glutamate receptors. FRAXA funded preclinical validation of this discovery in theRead more
Massachusetts Institute of Technology Researcher Mark Bear, PhD, Sees Success Developing Disease-Modifying Treatments for Fragile X Syndrome and Other Developmental Brain Disorders Finally, hope. And it comes from the lab of Mark Bear, PhD, Picower Professor of Neuroscience, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology Dr. Bear is building on the “mGluR theory” and applied insights gained by the study of Fragile X and other genetically defined causes of intellectual disability and autism with some success. His goal is to discover and facilitate the development of disease-modifying treatments for Fragile X and other developmental brain disorders. “Neurons in the brain communicate with each other at specialized junctions called synapses,” said Bear, who earned a BS from Duke University and a PhD in neurobiology at Brown University. “Such modifications are the basis for memory storage in the brain, and go awryRead more
Drug Tolerance and Dose Range Problems May Have Been the CulpritsAndy Tranfaglia and his dad, Mike Tranfaglia 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. Dosage problems are relatively easy to correct, but tolerance to the degree we observed may be a kind of fatal flaw, at least if we're talking about mGluR5 antagonists. The mGluR Theory of Fragile X is still probably correct; it's just that no one (least of all Novartis) expected tolerance to this drug -- indeed, I'm not sure they would agree that's what happened. I think we saw a much better response than most people because our son, Andy, was also on minocycline, effectively augmenting the response, and perhaps delaying the development of tolerance. This may be a clue to understanding the mechanism of tolerance,Read more
by Leslie Martini Eddy Saša Zorović first learned his son Anders’ had Fragile X syndrome when he was four years old. The diagnosis hadn’t come easily. Anders had been tested for Fragile X a year earlier and the results were negative. “We are not sure to this day why that happened. His geneticist suspected Fragile X and ordered the test, but it came back negative. We continued seeing other doctors and specialists, trying to get an understanding of what Anders had,” Saša said. A year later, another geneticist took a look at Anders and said with certainty, “He has Fragile X.” After a thorough examination of Anders and sorting through previous reports, another test was ordered. This time it came back positive. Anders had Fragile X after all. Anders showed symptoms of Fragile X early on. At 9 months, his very low muscle tone prevented him from sitting up straightRead more
Phase 2b Clinical Trial of Arbaclofen in Autism Seaside Therapeutics reports the study did not show improvement on the primary endpoint of social withdrawal, but it did demonstrate improvement on the Clinical Global Impression of Severity scale. Read the article: https://www.businesswire.com/news/home/20130501006067/en/Seaside-Therapeutics-Announce-Results-Phase-2b-ClinicalRead more
Question: How Do Families Decide Which Trial is Best for Them? Answer: Each of the trials has different requirements for joining, so many – if not most – people will only be eligible for one trial after screening. The best way to approach this is to call the clinic contact closest to your area and discuss this with him/her. Age, weight, current medications, behavior, and IQ are all factors. When will the Trials be Finished? It all depends on enrollment. Trials need to have a certain number of people (a number determined before the trial starts) complete the trial before they can analyze the data and present results to the FDA. It all depends on how many people sign up to participate. Is There Assistance for Travel? Many trials provide financial assistance for travel expenses. The amount depends on how far you have to travel. Please check with the coordinatorRead more
Treatment Trials As you probably know, three pharmaceutical companies are conducting clinical trials in Fragile X. Two Swiss giants, Novartis and Roche, are racing to get their lead mGluR5 antagonists to market, and U.S. startup Seaside Therapeutics is pursuing a compound which targets the brain receptor, GABAB. Novartis has large-scale Phase IIb/III trials of the drug AFQ056 well underway. Sites worldwide are enrolling adolescents and adults, with 35 more adults needed and recruitment of adolescents planned through Fall 2012. At this point, some participants have already completed the placebo-controlled trial and are now taking AFQ056, with the option of continuing it until it reaches the market. Novartis is also working toward a trial of AFQ056 for younger children with Fragile X. Roche completed a Phase II trial of its mGluR5 antagonist (currently with the catchy name of RO4917523) last year and is about to commence a larger Phase II trialRead more
On the eve of Thanksgiving, we want to thank everyone who has helped bring us so close to available treatments - and to take stock of where we are. by Michael R. Tranfaglia, MD Medical Director and Fragile X Parent Each year, we’ve described ever greater progress toward our ultimate goal: disease-modifying treatments and an ultimate cure for Fragile X. At times it must seem that this quest will take forever; however, the pace of research has truly moved into high gear in 2011! While FRAXA’s mission to find a cure for Fragile X is simple in concept, it is clearly a daunting task. To address the overwhelming complexity of this challenge, we have developed a plan of attack: • We fund high-quality basic research on the causes of Fragile X, which leads to possible treatment strategies (therapeutic targets). • We fund some of the finest neuroscientists in the worldRead more
With a $10,000 grant from FRAXA Research Foundation, Dr. Hessl at the University of California at Davis led a collaborative study to analyze the Aberrant Behavior Checklist (ABC) as an outcome measure for children and adults with Fragile X syndrome. Results published.
Three Researchers Honored at FRAXA 2008 Investigators Meeting Over 150 scientists from around the globe gathered in Durham, New Hampshire, for FRAXA Research Foundation's Investigators Meeting on September 21-24, 2008. They came from Australia, Canada, India, Turkey, the U.S., and eight European countries. Their common goal: "to share, collaborate and publish," in the words of FRAXA's Medical Director, Michael Tranfaglia, MD, to find effective treatments and a cure for Fragile X, the foremost inherited cause of mental retardation and autism. Most of the attendees were university-based professors, postdoctoral fellows, and graduate students who have FRAXA research grants. Also participating in the meeting were scientists from the National Institutes of Health (NIMH, NICHD, and NINDS), Neuropharm Group PLC, Hoffman LaRoche Inc., GlaxoSmithKline, Indevus, and Seaside Therapeutics, as well as 20 parents of Fragile X children. At the opening reception, FRAXA honored three investigators for taking extraordinary steps to advance research: FRAXARead more
Randy Carpenter, MD Principal Investigator with Mark Bear, PhD, MIT Co-Investigator (2007) Clinical development of mGluR5 Antagonists to Treat Fragile X Syndrome and Autism Seaside Therapeutics received a major grant from the NIH, with additional funding from FRAXA and Cure Autism Now (CAN) to develop STX107, a selective mGluR5 antagonist, as a treatment for Fragile X. Unfortunately Seaside has since discontinued development of STX107.Read more