FRAXA’s 2014 Top Goals

Complete Phase II/III Clinical Trials of mGluR5 Antagonists – and learn results

Currently two large pharmaceutical companies – Novartis and Roche – are conducting large-scale clinical trials of experimental new medications for Fragile X syndrome which target the mGluR5 pathway.  The Novartis trial has finished enrolling adults and adolescents, while a pediatric trial is set to begin soon.  The Roche trial is well on the way to completion as well, but is still enrolling some age groups.  FRAXA has been working diligently to educate families about these trials in the hopes of getting them completed as quickly as possible.  Our goal (of course) is to discover whether these new drugs could be effective treatments for Fragile X, and to see these trials through to marketing of mGluR5 antagonists for Fragile X.


Accelerate Clinical Trials of Investigational Treatments, based on research already funded by FRAXA

New treatment strategies have emerged and we are now working with a number of pharmaceutical companies to move to the next step: clinical trials. Examples include Neuren Pharmaceuticals, and Alcobra Pharma; both companies have announced exciting positive results from preclinical studies in Fragile X animal models (through FRAXA’a Drug Validation Initiative), and both are planning clinical trials.  There are many others!  FRAXA’s second 2014 goal is to build up the preclinical and clinical infrastructures to move these initiatives forward.


Develop and test new outcome measures for Fragile X and autism clinical trials

The current round of clinical trials is clearly struggling with inadequate outcome measures.  The FDA considers the Aberrant Behavior Checklist and the Clinical Global Improvement scale to be the standard assessments to detect responses to treatments in developmental disorders clinical trials.  However, these assessments are highly subjective, and do not measure subjects’ performance or behavior directly.  Ideally, we would like to have tests which a wide range of Fragile X subjects can do, which would give a relevant indication of that subject’s level of function, and which would respond to treatment with a disease-modifying therapeutic.  To develop better outcome measures, we plan to incorporate prospective new measures into upcoming treatment trials, especially those using available drugs, where trial design can be much more flexible.


Explore Existing Medications that research has shown might treat Fragile X, including “drug cocktails”

Existing, off-the-shelf medications like lithium, minocycline, and lovastatin have emerged as potentially disease-modifying for Fragile X.  These are drugs which were developed for other purposes and which have already been shown to be safe enough for general use.  Now FRAXA-funded research has raised the possibility that these medicines could treat not just symptoms, but actual core deficits of Fragile X.

The definitive way to demonstrate whether these drugs work in Fragile X is to try them in double-blind, placebo-controlled trials.  Trials tend to be quite expensive, but if we can raise the funds, FRAXA will undertake new clinical trials of existing medications during 2014.