Experimental medicine to define new mechanisms of neurodegeneration

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22/01/2025   |   Medical Research Council

Apply for UKRI / MRC UK Research and Innovation UKRI Logofunding to investigate the causes, progression and treatment of neurodegenerative conditions that give rise to dementia.

You must be based at a UK research organisation eligible for Medical Research Council (MRC) funding.

Your project must:

  • include an experimental intervention or challenge in humans
  • focus on a mechanistic hypothesis
  • be in partnership with industry

The full economic cost (FEC) of your project can be up to £5 million over a duration of up to five years. We will fund 80% of your project’s full economic cost.

Who can apply?

Before applying for funding, check the Eligibility of your organisation.

UK Research and Innovation (UKRI) has introduced new role types for funding opportunities being run on the new UKRI Funding Service.

For full details, visit Eligibility as an individual.

Who is eligible to apply

To be eligible to apply for this funding opportunity you must:

For applicants who do not have a contract of employment for the duration of the proposed project, by submitting an application the research organisation is confirming, if it is successful:

  • contracts will be extended beyond the end date of the project
  • all necessary support for the project and the applicants will be provided, including mentorship and career development for early career researchers

A research organisation may lead or partner on more than one application and applications may comprise more than one research organisation.

Individuals may be project lead on only one application. However, individuals can act as project co-leads on any number of applications.

Who is not eligible to apply

You are not eligible to apply for this funding opportunity as a project lead if you are based at an international research organisation. This does not include project leads from MRC Unit The Gambia or MRC/UVRI Uganda Research Unit at the London School of Hygiene and Tropical Medicine. Before applying for funding, check the Eligibility of your organisation.

International applicants

You can include international applicants as project co-leads (international), where they will make a major intellectual contribution to the design or conduct of the project. The contribution and added value to the research collaboration should be clearly explained and justified in the application, see Applicant and team capability to deliver.

Equality, diversity and inclusion

We are committed to achieving equality of opportunity for all funding applicants. We encourage applications from a diverse range of researchers.

We support people to work in a way that suits their personal circumstances. This includes:

  • career breaks
  • support for people with caring responsibilities
  • flexible working
  • alternative working patterns

Find out more about equality, diversity and inclusion at UKRI.

What we’re looking for?

You can apply for funding to support experimental medicine projects that are conducted in living humans, optimally in partnership with at least one industry partner. Your project should be ambitious and challenge-led, based round a clearly articulated gap in our understanding of neurodegenerative disease mechanisms. Although not primarily aimed at discovering new treatments, the approach should have a clear path to clinical impact.

Projects should draw on existing scientific, technical and clinical expertise, clinical research infrastructure and have significant links with industrial partners.

Successful projects will produce new mechanistic insights, including those that may:

  • identify opportunities to modify disease pathways
  • enable the future development of novel therapeutic or early diagnostic approaches
  • discover novel exploratory biomarkers to stratify disease and monitor disease progression
  • identify disease subtypes and refine treatments based on precision medicine and stratification through a deeper understanding of novel disease mechanisms

Applications should primarily focus on neurodegenerative conditions that give rise to dementia. However, applications may also include a focus on related neurodegenerative diseases which share similar underlying mechanisms where there is a significant knowledge gap.

In addition to generating new knowledge about pathogenesis, projects must be of high potential value to industry research and development, addressing known challenges that contribute to high failure rates in treatment development and helping to de-risk early phase dementia trials.

Evidence of public and patient involvement is essential.

Projects are particularly welcome that:

  • focus on pre-clinical, early-stage, or emergence of disease
  • widen patient involvement (including those with comorbidities and other understudied groups)
  • address gaps in our understanding of disease mechanisms in underrepresented populations
  • bring together expertise, tools and interventions from other relevant disease areas and disciplines, for example vascular and metabolic diseases
  • drive forward high-risk but high-reward research that pursues novel disease pathways
  • draw on, and validate, novel tools for experimental medicine studies in neurodegeneration(although tool development should not be a primary aim)

What your application must include

Your application must involve an experimental investigation in humans at its core, which has been designed to validate a mechanistic hypothesis. This should include an intervention or challenge, such as:

  • pharmacological
  • immunological
  • physiological
  • psychological(linked to sustained biological read-outs)
  • infectious

Activities we support

The following types of work are eligible for support:

  • the use of novel readouts or technologies related to early evaluation of a pathogenic mechanism
  • the use of drugs, other interventions or measures with established safety profiles in new settings or conditions (for example, repurposing drugs to probe disease mechanism)

We also support work activities that include the characterisation or phenotyping of subjects using samples from clinical studies or at-risk cohorts where there is a clear link to a current experimental medicine strategy. However, this should not be the primary or sole focus of your application.

Limited, hypothesis-driven, retrospective sample analysis may be included at the start of the project to improve the design of the interventional, experimental medicine study. Milestone criteria should clearly detail what data is required from the confirmatory analysis for the project to progress.

Prospective, nested studies within a larger cohort trial may be eligible provided they:

  • can demonstrate added value
  • are exploring disease mechanisms
  • test a novel hypothesis
  • address a different question to the main study

Competitive applications will aim to address a clear mechanistic question and provide strong rationale to justify the suitability of the research and experimental system proposed to test the presented hypothesis.

Activities we do not support

The following activities are ineligible for support through this funding opportunity:

We encourage you to contact us first at ExMedND@mrc.ukri.org to discuss your application.

Collaborations and connectivity

Projects should be guided by patient and carer perspectives, creating strong pathways to impact, addressing common goals of the wider research and patient communities.

Projects must build on existing scientific, technical and clinical expertise, clinical research infrastructure and have significant links with industrial partners. Evidence should be provided of the nature of existing partnerships that underpin the application and the value these add.

Applications must include industry partners. This may be in terms of access to expertise, technologies, reagents or funding. You will need to complete the Industry Collaboration Framework (ICF) section. Find out more about ICF.

We anticipate that the funded projects will form a portfolio of complementary activity that will build on, and develop, existing scientific and technological platforms, resources and expertise within long-term investments across the UK, including and not limited to:

These investments provide various relevant resources for experimental medicine studies, including:

  • clinical research facilities
  • infrastructure for brain imaging (including MRI, PET and MEG)
  • pre-clinical and clinical cohorts for recruitment
  • multi-modal data analysis platform (DPUK Data Portal)
  • tools, templates and frameworks for streamlining study set up

Projects that will benefit from these resources are encouraged to make contact directly.

This funding opportunity will support high impact groupings that bring together the requisite knowledge, skills and infrastructure to address the challenge identified. Projects funded through this opportunity will work together, and with other relevant investments in the landscape, to share knowledge and best practice and to identify and exploit synergies.

Duration

Projects can be of duration of up to five years. You should justify the timescale of the project in the context of the proposed work.

Milestones

Milestones allow us to mitigate risk and support potentially high-risk projects.
Experimental medicine awards will typically have at least two milestones with specific success criteria that reflect major progress points and allow mechanistic hypotheses to be laid out and evaluated as the project progresses.

Your milestones should also provide a realistic indication of timelines for key steps, such as regulatory steps, study team recruitment, participant recruitment, study completion and data analysis.

Milestone success criteria should be SMART (specific, measurable, achievable, relevant and timely), and detail any robust go or no-go criteria. For all projects, it is advisable to structure the project so that the critical questions are addressed as early as possible in the plan.

Funding available

The full economic cost (FEC) of your project can be up to £5 million. You should justify the resources needed in the context of the proposed work.

We will fund 80% of the full economic cost and 100% of permitted exceptions.

Find out more about full economic costing.

What we will fund

You can request funding for costs such as:

  • a contribution to the salary of the project lead and co-leads
  • support for other posts such as research and technical staff
  • research consumables
  • equipment
  • travel costs
  • data preservation, data sharing and dissemination costs
  • estates and indirect costs

You can also request costs for work to be undertaken at international organisations by international project co-leads. We will fund 100% of the eligible costs.

The total of such costs requested for international applicants from developed countries (those not on the OECD DAC List of ODA Recipients), India and China, must not exceed 30% of the total resources requested.

There is no cap on costs requested for international applicants from development assistance countries (DAC).

For more information on international costs and what we will and will not fund see costs we fund and the Collaborate with Researchers in Norway guidance.

What we will not fund

We will not fund:

  • research involving randomised trials of clinical treatments
  • costs for PhD studentships
  • publication costs
  • funding to use as a ‘bridge’ between grants

Team project partner

You may include team project partners that will support your research project through cash or in-kind contributions, such as:

  • staff time
  • access to equipment
  • sites or facilities
  • provision of data
  • software or materials
  • recruitment of people as research participants
  • providing samples, such as human tissue, for the project

Each project partner must provide a statement of support. Your application must involve industry partners and they must provide additional information if the team project partner falls within the industry collaboration framework.

Find out more about subcontractors and dual roles.

Who cannot be included as a team project partner

Any individual included in your application with a core team cannot also be a project partner.

Any organisation that employs a member of the application core team cannot be a project partner organisation. This includes other departments within the same organisation.

If you are collaborating with someone in your organisation, consider including them in the core team as project co-lead, or specialist. They cannot be a project partner.

Supporting skills and talent

We encourage you to follow the principles of the Concordat to Support the Career Development of Researchers and the Technician Commitment.

Trusted Research and Innovation (TR&I)

UKRI is committed in ensuring that effective international collaboration in research and innovation takes place with integrity and within strong ethical frameworks. Trusted Research and Innovation (TR&I) is a UKRI work programme designed to help protect all those working in our thriving and collaborative international sector by enabling partnerships to be as open as possible, and as secure as necessary. Our TR&I Principles set out UKRI’s expectations of organisations funded by UKRI in relation to due diligence for international collaboration.

As such, applicants for UKRI funding may be asked to demonstrate how their proposed projects will comply with our approach and expectation towards TR&I, identifying potential risks and the relevant controls you will put in place to help proportionately reduce these risks.

Find further guidance and information about TR&I, including where you can find additional support.

Visit funding web page
(https://www.ukri.org/opportunity/expression-of-interest-experimental-medicine-to-define-new-mechanisms-of-neurodegeneration/)

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