Research Strategy

Introduction

The NPRF was established in April 2011 to raise funds to spend on research in to the disease and promote UK trials of promising therapies for Niemann-Pick Type C (NPC).  It is the only UK charity dedicated to funding research into NPC.

NPC is a rare, fatal, autosomal recessive lysosomal storage disease characterized by progressive neurodegeneration.  There are reported to be only 1,000 cases currently diagnosed worldwide of which approximately 100 are in the UK.  There are a number of clinicians and research professionals worldwide knowledgeable in NPC and there are a number of laboratories that conduct research into this currently incurable condition.  Although some research and trials are funded by public bodies, the professional NPC network also relies for funding on patient-inspired charitable bodies.  The purpose in publishing this Research Strategy is to inform potential clinical or research applicants of the priorities and goals of the NPRF and therefore to enable them to make suitable grant applications to the charity.

The NPRF is a member of the Association of Medical Research Charities (AMRC).  Membership of the AMRC requires charities to publish a Research Strategy and dictates strict governance procedures for grant-giving.  One benefit of AMRC membership is that awards to higher education institutes should attract a government funded overhead contribution under the charitable support research fund.

The NPRF has established the SWAT team (“Scientists Working to Accelerate Therapies”) that includes some of the leading NPC scientists and clinicians in the UK.  There have been several meetings of the SWAT team at which the institutions that are in receipt of NPRF grants have presented their research. There has been an immense benefit of bringing scientists, clinicians and researchers together to discuss the research being undertaken and link evidence gathered in the laboratory with the real clinical progression of the disease and available treatments.

NPC is a very rare disease and as such it is difficult to garner widespread support and funding.  The NPRF expects that the funds that it will have available to support research will be relatively modest compared to the budgets of large-scale research projects. The charity has been established as a foundation with minimal overheads to ensure that it represents a very efficient channel for donors wishing to support NPC research.  To maximise the benefit of the grant funding that the NPRF will make available, the charity has designed its Research Strategy with the following principles;

  • Priority will be given to projects where the charity’s grant will have the most impact, for example where an existing lab conducting NPC research can accelerate research through small targeted grants leveraging the existing knowledge and work being conducted by the lab,
  • Although research to understand basic science of NPC is important, such projects would need to demonstrate a relevance to improving treatment of the disease,
  • Projects must be able to demonstrate that grant funding from the NPRF is additive, i.e. that there are no obvious or better sources of funding,
  • Although the NPRF will consider applications from outside the UK on an exceptional basis, it is expected that most successful applications will come from UK-based scientists and clinicians,
  • Projects which enable advances being made in other countries (for example potential therapy development) to be made available in the UK will be of particular interest to the charity,
  • The NPRF expects dissemination of outputs and outcomes to both lay and professional audiences and requires its support to be acknowledged in published papers.

Why is research necessary?

NPC is a rare, fatal, genetic disease leading to neurodegeneration. Although there is one drug currently approved in over 40 countries, (including the UK) for affected patients (Miglustat), this drug is not effective in all patients, it does carry potential side-affects and it is not a cure, although it has been shown to slow down disease progression in some patients. A number of promising therapies are either in trial or looking to go into trial in the next year. This includes a trial at the NIH in America, which started in January 2013, administering Cylodextrin (HPBCD) initially via an Ommaya Resevoir, but following complications via a lumbar puncture. This small safety trial is was originally only open to US patients but has this year begun to roll out internationally, including the UK. However, numbers involved across the multiple sites will be limited which leaves currently diagnosed patients in limbo. In addition, CTD Holdings are also looking at rolling out a trial internationally using Trappsol Cyclodextrin and Orphazyme are looking to start a trial with their small molecule Arimoclomol this year. Again entry criteria are yet not known, but a number of current patients are expected to miss out. The NPRF is therefore keen to ensure that research into other potential therapies is continued that may provide an alternative or complimentary treatment that will be either better at slowing or halting disease progression than Miglustat or can actually reverse existing neurological deterioration and can potentially be used in combination with Miglustat. Such progress will only be achieved through research, both at the basic scientific and also the clinical level. The NPRF has continued to raise funds to help support research and trials that will find improved therapies and ultimately a cure for this terrible disease.

Much of the early NPC-related research was mainly undertaken in the United States, although there are also excellent scientists and clinicians in the UK, who the NPRF has funded over the last 5 years. The NPRF is willing to work collaboratively with other charities, individuals or companies who share the same goals.

The NPRF expects that on average grants will be for around £50,000, which is a reflection of its fundraising capacity. However, following more successful than projected fundraising events the NPRF maintains a flexible approach and given a proven track record from an applicant, will accept applications for larger amounts, particularly in collaboration with others. We appreciate that is level of funding will preclude some of the most popular types of grants made by other charities, including multi-year programmes such as post-doctoral grants.

Priority research areas

The following areas have been identified as priority areas for research funding;

  • Accelerating research and alleviating bottlenecks and impediments to progress in research. Labs that rely on project funding for their NPC research may experience funding shortages for pilot projects emanating from other research. The NPRF is keen to support labs with excellent track records in NPC research to increase the labs capacity to accelerate research. The NPRF is committed to finding a treatment for the current generation of NPC patients and hence time is of the essence.

  • Laboratory based research into the effectiveness of compounds thought to have a potential beneficial therapeutic impact on NPC. The development of new drugs from scratch takes many years and costs millions of pounds. This solution is highly unlikely for a rare disease with a very narrow potential market for a successful treatment and in any event is unlikely to provide a solution for today’s generation of patients. The focus of investigation for rare diseases has shifted to research on existing known drugs or compounds, to test their efficacy in rare disease models. Funding for such activities is within the reach of rare disease charities and the time scales are far shorter. The NPRF is keen to support progress in this area, either for single drug therapies or for combination therapy.

  • Given the recent advances by pharmaceutical companies and potential trials, the NPRF will continue to monitor progress of these trials very carefully and is in contact with the doctors and families around the world. The NPRF is keen to ensure that if a potential therapy is proven to be a promising therapy for NPC, it is made available to patients in the UK. For example Cyclodextrin, which is currently designated as an orphan drug in both the US and the EU. The NPRF is keen to support any trial of CD or other promising therapies in the UK and/or to promote UK patient participation in trials or to promote the creation of a second clinical trial centre in the UK if appropriate in the future.

Types of grants

The NPRF expects to have only modest funding available to support research projects and its Research Strategy is therefore to focus on grants that are highly focused and are likely to yield disproportionate benefits compared to the sums expended;

  • Pilot studies within existing NPC labs. The NPRF has identified a potential gap that it will seek to fill with small-scale grants aimed at funding pilot projects based on avenues of research that emanate from existing labs NPC research. The NPRF believes it can act relatively fast in considering and approving such applications and will enable research to proceed that may otherwise have to wait for larger grant applications which may take a considerable time to be approved. For labs with an excellent track record of research in the field, such pilot grants may take the form of core infrastructure funding of technicians or consumables. Successful applicants will need to demonstrate a first class track record of research in the field and that the grant funding will enable its research progress to be accelerated.

  • Project grants. The NPRF will make available project grants to support laboratory research into the basic science of NPC provided the project can demonstrate relevance in developing a treatment for the disease. The NPRF will consider grant applications in collaboration with other funding bodies or as top-ups for projects that require incremental funding to draw to a successful conclusion.

  • Clinical trials. The NPRF will consider grant applications from clinicians seeking to investigate clinical trials of potential therapies into NPC. The grants may be to fund support for the clinician in applying for approval for the trial or for a proportion of the direct costs of the trial.

Applications for funding from the NPRF must demonstrate how the research fits with the charity’s research strategy and priority areas. However, these priority areas are not exhaustive and promising work outside these areas can still be considered.

Grants will largely be for projects that are investigator instigated although in future the NPRF may seek applications that cover areas of specific interest. Grants will only be available for research where the principal investigator is based in a recognised research centre, university or hospital.

Available funding

The funds available to the NPRF are likely to be limited and dependent on the efforts of informal fund raising, donations by other foundations and charities etc. Whilst the overheads of the charity are small, the NPRF will not commit to raise funds to cover research requests, but will only grant funds that it has already at its disposal. It will advertise Research Grants on its website as and when it has funds available, although applications at any stage are welcomed and feedback will be provided as to the ability to fund.

With an ever-changing picture into potential therapies and trials into NPC, the NPRF will review its Research Strategy every year to ensure that funds raised are being utilised in the most productive way to achieving its main objective of helping facilitate the development of potential therapies for NPC that either slow down the progression of the disease or actually reverse existing symptoms.

Application process

The process for applying for a grant from the NPRF is set out below;

  1. Initial application. Submit a summary of the grant sought including;

    1. Budget,

    2. Purpose, a description of how the funds would be applied, over what period and what could be achieved by the lab that would not otherwise have been possible,

    3. Project success, subjective and/or objective measures that can be pre-determined at the start of the funding and can subsequently be tested to provide a means of assessing the success of the funding.

    4. Benefits to the charity, describe any publicity or citations, which will be available to the Charity as a result of the grant funding.

    5. NPC implications, describe how the grant will help in researching NPC.

    Unsuccessful applicants will be provided with feedback on the reasons their application was not successful.

  1. Full application form. Following the initial application stage, successful applicants will be required to submit a Full application form. This application will be subject to peer review by external examiners and consideration by the charities Scientific Advisory Board. The Scientific Advisory Board will consider how well the grant meets the charities objectives and will make a recommendation to the NPRF’s trustees. Any grant offered will be made available only after the Charity’s Terms and Conditions of Grant and Award Letter have been signed by an authorised representative of the applicant.