Updated Scope: Therapeutics & Tools

August 28, 2017

The Institute has updated its scope with new definitions of therapeutics and tools for 2018 programs (programs with 2018 in the title). Please check below to ensure your idea falls within our updated scope.

Previous scope definitions are still in use for all 2017 programs, and are listed on the What We Fund page.

New for 2018 programs

Therapeutics definition:

The Institute defines a therapeutic to be a pharmacological approach (including small molecules, biologics, cell therapies and vaccines, including drug repositioning and repurposing), medical device, surgical intervention, or magnetic or electrical brain stimulation. Therapeutics can be for symptomatic relief, disease modification, or prevention. Complementary approaches such as exercise, acupuncture, music, dietary and nutritional supplements are not considered therapeutics. Identification of novel therapeutics is in scope (e.g., high throughput compound screens); however, identification of novel targets is out of scope. Identification of therapeutic targets is not in scope, including genes implicated in disease.

Tools definition:

Tool: An item that accelerates development of therapeutics, e.g., imaging techniques or reagents, biomarkers, and diagnostics.

  • Tools must have direct impact on the translational development of therapeutics (as defined by the Institute, i.e., target validation to phase IIa clinical trials) for neurodegenerative diseases of aging and will be valued only on their ability to do this.
    • Any value the tools contribute to basic research will not be taken into consideration. For example, tools will not be valued for their ability to identify new targets or understand disease mechanisms.
  • Projects covering only the discovery/identification of a tool are out of scope.

Notes about biomarkers

  • Biomarkers must be being developed for human disease diagnosis, prognosis, for patient stratification to clinical trials or to predict response to therapies (surrogate for a clinical endpoint).
    • Biomarkers should measure pathology of the disease (e.g., fluid, imaging or tissue biopsy derived biomarkers) and not be based on behavioural phenotypes (e.g., gait or grip strength).
    • Genetic biomarkers including somatic mutations, SNPs, epigenetics and gene products are in scope if they meet the other eligibility criteria.
  • If the project includes biomarker identification:
    • The project must also include experiments to validate the biomarker.
    • All the samples/data necessary for identification and validation must already be available/collected unless there is sufficient justification to collect new samples/data (e.g., samples cannot be stored).
    • Validation of biomarkers must occur in a well-characterized human subjects/samples/data. This validation must be in samples/data from different subjects than those used to identify the biomarker.
    • Post mortem tissue can only be used for validation of biomarkers previously identified in living subjects.

An identified biomarker is defined by the Institute as one that meets the following 4 conditions:

1.  Specific item(s) or signature to be measured can be defined;

  • For e.g.,
    • Presence of a particular bacterium
    • Disease-specific EEG signature
    • Specific brain structure with reduced volume
    • Single protein increased
    • Precisely defined fingerprint
      • If the biomarker is a fingerprint of a family of proteins or a signature of brain volume changes, the precise fingerprint or signature to be replicated must be previously determined. For e.g., omics studies for the purpose of identifying biomarker patterns or signatures are out of scope.
    • Exact identities of multiple individual factors that may be useful individually or as a specific composite
  • It is not in scope to know that a family of proteins is affected or that brain volume is changed overall, if the specific item or signature that is the biomarker cannot yet be specified. For example, a single protein is not considered an identified biomarker if only the family of proteins were previously identified to be affected

2. In what it will be detected (e.g., which tissue/fluid), using what assay, and for what disease, can be clearly stated;

3. Specific item(s) (or signature) to be measured has been shown to be detectable in humans or human-derived samples/data in the tissue/fluid to be tested;

4. Compelling data exists to justify moving to validation (as defined by the Institute).

  • The most compelling data is likely in humans or human-derived samples/data with a relevant disease
  • The most compelling data will likely allow for a power calculation
  • Data from pathophysiologically relevant animal models could be considered if those animal data are compelling

Biomarker validation is defined by the Institute as:

  • Testing a previously identified biomarker in a sufficient number of appropriate, comparable, well-characterized human subjects/samples/data to determine whether it is a sensitive and/or accurate biomarker.
    • If the proposed assay is different than the one used for initial biomarker identification, or if the assay will be used in a different type of specimen (e.g., different tissue/fluid or different species) then preliminary data must be provided to demonstrate that the assay works appropriately. For example, if a biomarker was identified using an assay in CSF and you are proposing to use the same assay to validate a biomarker in blood, there must be preliminary data demonstrating the assay works in blood.
    • Replication studies are not considered to be validation, e.g., using subjects with a different disease stage, or subjects on different drug regime if that regime could affect the biomarker.

For cognitive assessment tools and clinical assessment instruments

  • If developing a cognitive assessment tool or a clinical assessment instrument, the tool must be being tested in patients with a relevant disease.
  • Requires discussion of why the new assessment would be better than existing ones.