FRAXA Grants and Fellowships for Fragile X Research – 2014 Priorities

Funding Priorities for 2014 Grant Cycle

We anticipate particularly keen competition for funding in this grant cycle. Challenging economic times inevitably force us back to fundamental principles, and so our overall priorities for 2014 grants will be to bring new, high-quality scientists into the Fragile X field, and to promote translational, preclinical, and clinical research with the greatest chance of improving therapeutics for those living with Fragile X.

Here are a few key implications of these policies:

  1. We want new ideas!  The mGluR Theory is now being tested in the clinic; we do not anticipate funding any major new projects investigating mGluR5 function, although there are many possible spin-off projects which could be the basis for successful applications.  Likewise, we do not assign a high priority to studies of every element of mGluR-coupled signaling pathways, unless the topic of study is an especially druggable target.  Most components of signaling pathways in the brain are also involved in cell cycle pathways outside the CNS, rendering them poor targets for Fragile X therapeutic development.
  2. For this same reason, our enthusiasm for high-throughput screens is quite low.  We have now funded many such screens, and the “hits” have mostly been cancer drugs with unacceptable toxicity.  We have also found that most academic labs struggle with the follow-up validation of leads generated by such studies, which greatly reduces their value.  Naturally, we are willing to consider innovative proposals which seek to overcome these limitations, but please check with us before applying.
  3. We want new people!  Established scientists in the Fragile X field will face long odds in our application process this year, unless the proposed research has obvious near-term promise for development of Fragile X therapeutics.  We are pleased to see that this field has grown tremendously over the past 10-15 years, but FRAXA can only afford “seed money”, not ongoing maintenance of academic labs.  Since it is a major priority for FRAXA to bring a steady stream of new blood into this field, a scoring advantage will be granted to new applicants (this has been the case for many years, but the proportion for this scoring factor is going up this year).  In addition, previous grant recipients whose work has not produced publications will face still longer odds, since we will be incorporating a score for productivity into all applications from previous grantees.
  4. We want a range of translational and clinical projects.  We see FRAXA Postdoctoral Fellowships as the appropriate venue for (relatively) more basic work, but the minimum level of “translational relevance” required for successful applications continues to rise.  The net effect of continuous advancement in the field is that only very translational research, likely with some preclinical proof-of-principle experiments, will be funded, even in this program.  Studies of the normal function of FMRP, without examination of the disease state, are too basic for any kind of FRAXA funding at this point.
  5. Program Grant applications must be exceptionally clinically oriented to be successful in this environment.  Accountability and deliverables will be our primary criteria for awarding FRAXA Program Grants in 2014 — at a minimum, successful applicants should be conducting preclinical testing of novel therapeutics in Fragile X model systems.  We always appreciate projects with multiple goals; for example, a study which develops an enhanced model while also using new compounds to attempt phenotypic rescue.
  6. Ideally, we would like to spend our entire Program Grant budget on clinical trials of available agents, possibly in combination trials, and hopefully with testing of improved outcome measures built into study protocols.  Biomarkers and other enhanced outcome measures are an especially high priority, but we do not believe that outcome measures can be developed in a vacuum.  Since we need outcome measures that respond to treatment, we believe the only way to properly validate outcome measures and/or biomarkers in Fragile X is in the context of clinical trials.  However, the kind of placebo-controlled trial required to demonstrate both efficacy of a particular compound (or combination of compounds) and usefulness of one or more outcome measures is probably prohibitively expensive.  Thus, we are open to creative alternatives.  For example, an open trial of an available agent like lithium or minocycline (or both) combined with pilot studies of potential outcome measures and biomarkers could provide useful data.  Essentially, we are trying to remove the placebo effect from clinical trials by utilizing totally objective assessment methods which are not susceptible to the placebo effect.  So, placebo control groups may not be necessary to study potential response of biomarkers to drug treatment—correlation of clinician-rated response to change in biomarker status could be sufficient (and much more cost effective) in some cases.

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