Advancing Research

December 13, 2014


How do we choose which research projects to fund? What exactly happens behind the scenes to ensure we make the best possible investments in Rett research?

We realize this post is long, but the subject is vital and our thoughts extensive.  We want you to understand how chooses research projects, and to know what safeguards we have in place to ensure the integrity of our rigorous scientific program.

  1. Understanding the Grant Making Process
  2. Our Grant Programs
  3. The Review Process
  4. Peer Reviews
  5. Award Approvals and Activities.

Understanding the Grant Making Process.

Twice a year, we ask researchers worldwide to submit their research project proposals to us. We have them reviewed for scientific merit through a process of peer-review to help us identify projects that have high potential to advance research and accelerate treatments.

Since we’re going through the process right now, we wanted to let you know what the Research Team at does to ensure we’re finding innovative research projects.

Projects that have: 
•    the potential to make basic discoveries;
•    open up therapeutic avenues to explore;
•    open doors to new compounds to test in animal/preclinical studies;
•    all in hope, of translating these findings to human/clinical studies for actual treatments. 

Our Grant Programs

Call for Proposals.

We start the grant making process by sending out a “Call for Proposals”. We have built a Rett researcher community and send them information through an email that we are ready to start accepting letters of intent.

A letter of intent is a brief communication that a researcher writes to give us a general overview of the project s/he would like to pursue.

In the winter, we ask for proposals that have a translational research angle which would utilize the HeART (Help Accelerate Rett Therapeutic) grant mechanism.

A Therapeutic could mean a drug compound or a type of therapy (physical, cognitive, communication), or assessments for outcome measures or early diagnosis. Last winter, we asked for proposals to our new Neuro-Habilitation Program (link to blog).

In the summer, we have our bigger call for proposals. Researchers can apply to all our programs (training fellowships, basic research, and translational).

Grant Programs.

Before we move on, we wanted to expand a little bit about how grant programs evolved.

Overall, our Grants Program is aimed towards advancing therapeutic strategies to get treatments out to the Rett community.

When the foundation first started, the cause of Rett syndrome biology was unknown, so the foundation had to invest in Basic Research Grants, which yielded the discovery that MECP2 mutations were associated with Rett syndrome. 

We also invested in research that went into understanding what MeCP2 normally does in the neuron and brain, effecting neuronal networks and the central nervous system.

We invested in mouse models so we could investigate how mutations in MECP2 effect development and so we could use these models in later drug development studies. Besides needing these basic discoveries, we created a fellowship program to build the bench of future Rett researchers. We need to recruit talented young scientists that we hope would one day have their own lab dedicated to Rett syndrome research.

We have already talked about the HeART grants, but we also have a larger translational research grant mechanism, Advanced Neurotherapeutic Grants of Excellence (ANGEL). The ANGEL grants are deemed for more extensive preclinical animal studies or for human clinical trials.

Essentially we have two Research Grant Programs, each with their own Starter and Enabling Grant mechanisms that complement one another with goals to facilitate or catalyze the translation of basic research out of the lab and into the clinic (see image above).

Who can apply?

We encourage all ideas. We put out calls for proposals and encourage all researchers worldwide to answer. We don’t just fund the same people over and over again. We have given awards to over 150 researchers in 17 countries.

We accept qualified, scientific proposals from academic institutions, existing, private, early-stage pharmaceutical and biotechnology industries (if a clear need for non-profit funding to support the project is demonstrated and justified) and other non-profit organizations worldwide.

The Review Process prides itself on a fair and accurate review of each and every proposal received. The Scientific Review Board (SRB), whose primary function is to participate in the grant review process, is comprised of nearly 150 experts in Rett syndrome and related disciplines.

In order to achieve a high level of due diligence, we employ a two-step application process and rigorous peer review where applicants first submit a Letter of Intent described above as the answer to the Call for Proposals.

The LOI is reviewed to make sure the project does indeed answer the call specifics. After review of the LOI, we contact the investigator to invite or decline a full application.

The Peer Review Process begins with staff conducting a quality control review of all applications submitted before SRB members are assigned to specific proposals based on their specific areas of expertise. Each proposal is assigned to two Reviewers who provide a written critique.

At our in-person Grant Review meeting, we generally have a review panel comprised of 10-20 experts in Rett syndrome and related disciplines, including the research team. Each application is introduced by the two main Reviewers, who provide an open discussion of their written critiques and welcome additional comments from the whole panel. Following the discussion, Grant Reviewers provide a confidential score using a provided scoring sheet.

After the Grant Review meeting, the applications are ranked according to score and overall scientific merit. The proposals are then programmatically reviewed, to ensure they work toward prioritized areas of research that is not already filled by the foundation.

After both reviews, the Chief Science Officer (CSO) and the Manager of Grants and Research then makes funding recommendations and explains each proposal in detail to the Board of Trustees and requests formal Board approval.

More on the Peer Review Process in General.

"To maintain our edge… we’ve got to protect our rigorous peer review system and ensure that we only fund proposals that promise the biggest bang for taxpayer dollars . . . that's what's going to maintain our standards of scientific excellence for years to come."

Remarks by President Barack Obama on the 150th Anniversary of the National Academy of Sciences, April 29, 2013


What is Peer Review?

Like the NIH, we follow a process whereby submitted grant applications are evaluated on the basis of a process that is fair, equitable, timely, and free of bias.

Who are the peers?

The Scientific Review Board (SRB) is made up of nearly 150 experts in Rett syndrome and related disciplines. SRB members have positions either in academia as professors (from assistant to full) or biotech/pharmaceutical industries, and are considered experts in their fields. These board members are volunteers and provide their time and expertise to evaluate lengthy applications, write critiques, and attend a meeting we hold.

Sometimes, SRB members themselves may apply and have a grant in review. In these cases, we ask that they are not included in the grant review process to ensure that the panel of reviewers is free of bias.

What is asked of Peer reviewers?

We ask reviewers to read the entire application, which consists of bios of the Primary Investigator (the applicant) and any of his/her lab personnel, the requested budget, and the research plan.

Because we are looking for scientifically compelling, logical, and well-crafted research proposals that fit within the requested budget, we ask that reviewers score and provide a written critique in the following areas:

  1. Significance and importance of overall scientific aims
  2. Relevance of project to the cause, cure or treatment of RTT and its complications
  3. Strength of hypothesis
  4. Feasibility of specific aims
  5. Strength of research design and methodology
  6. Qualifications of PI, Sponsor, resources, and environment

To score an application, we follow the NIH scoring system:


Score Descriptor Additional Guidance on Strengths/Weaknesses
1 Exceptional Exceptionally strong; essentially no weaknesses
2 Outstanding Extremely strong; negligible weaknesses
3 Excellent Very strong; only some minor weaknesses
4 Very Good Strong but numerous minor weaknesses
5 Good Strong but at least one moderate weakness
6 Satisfactory Some strengths; some moderate weaknesses
7 Fair Some strengths but at least one major weakness
8 Marginal A few strengths; a few major weaknesses
9 Poor Very few strengths; numerous major weaknesses

Minor Weakness: An easily addressable weakness that does not substantially lessen impact
Moderate Weakness: A weakness that lessens impact
Major Weakness: A weakness that severely limits impact

Are there other funding agencies perform peer review?

This is not an exhaustive list, but includes well-known government agencies and private organizations.

  • National Institutes of Health
  • National Science Foundation
  • Simon Foundation for Autism Research Initiative
  • American Cancer Society
  • Michael J Fox Foundation for Parkinsons’s Research
  • Alzheimer's Drug Discovery Foundation

Award Approvals and Activities.

Applicants are contacted with the outcome of the Grant Review and are provided a summary of the comments on their application.

For those applications approved for funding, we ensure we have all the necessary paperwork to activate the award. In our case, we actually don’t fund the individual applicant because the funds are sent to the institution.

We make sure we partner with the institution and that the applicant has access to the awarded funds. The institution is eligible to receive indirect costs as they significantly support the individual.

Once the project is started, we work closely with each awarded researcher to obtain regular updates and progress reports on their work to ensure that all funds are used as intended, as described in the Policy Statement on Research Support.

Many of our grants have two year timelines, and support for the second year of the project is dependent upon the successful submission of scientific progress reports and a financial report in the first funding year.

In order to ensure research is progressing, the Research Team also holds Program Review Meetings. Instead of sending us a written progress report, we ask funded investigators to present their progress in a private seminar.

We’ve held meetings in Boston, San Diego, Houston, and Birmingham so far. We believe meetings like these let our funded investigators know that we care about them, their work and hope to foster communication and collaborations within our Rett researcher community.

The Takeaway.

We hope this blog has answered questions you may have had about how we choose a research project to fund. There are many people behind the scenes that work to ensure that the Research Investments of are good ones. We made so much progress in research, but continue to strive to advance research and help all those affected by Rett syndrome.

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