RFP- Neuroimaging and CSF Biomarker Program Grant

The RFP from the Alzheimer's Drug Discovery Foundation aims to develop crucial biomarkers for Alzheimer's and related dementias. Key focuses include creating novel PET ligands, supporting CSF biomarkers, and validating MRI techniques. The initiative prioritizes innovative biomarkers of neuroinflammation and synaptic integrity, emphasizing those that aid in early detection, disease progression monitoring, and differentiation between dementia subtypes, ultimately enhancing drug development and clinical applications.

Funding Opportunity Description
The aim of this RFP is to develop biomarkers for which there is a clear clinical need in Alzheimer's disease and related dementias.
Specifically, this RFP focuses on:

• Developing novel PET ligands for clinical trials
• Supporting novel CSF biomarkers
• Validating innovative MRI approaches in larger cohorts
• Developing novel measures of functional activity such as EEG
• Peripheral biofluids and digital approaches are supported through the Diagnostics Accelerator RFP.

Novel biomarkers of neuroinflammation and synaptic integrity are considered high priority. Other target areas of interest include:
Neuronal loss.Vascular injury and blood-brain barrier integrity.Mitochondria and metabolic function.Protein misfolding/proteostasis.Oxidative stress.White matter changes.Other novel targets supported by compelling biological rationale and connection to disease.
The ADDF has limited interest in CSF measures of amyloid and tau.
Funding Priorities
The ADDF focuses on advancing drug development for Alzheimer’s and related dementias and the biomarker tools that aid in this process. This RFP prioritizes biomarker programs that define a specific use and have potential for commercial and clinical translation, with an emphasis on clinical trials (see the Evaluation section below). The RFP supports advancement of neuroimaging and CSF biomarkers that can do one or more of the following:
Demonstrate target engagement for novel therapeutics: Biomarkers that can serve as direct measures of target engagement for novel drugs in clinical development. High priority will be given to projects advancing biomarkers that can be used as specific companion biomarkers for therapies currently in the development pipeline. Identification of such therapies strengthens an application.Detect signs of disease earlier and monitor progression: Programs developing sensitive biomarkers that can detect disease earlier than currently available biomarkers. This includes biomarkers that can predict and monitor conversion from cognitively healthy to mild cognitive impairment (MCI) or MCI to Alzheimer’s disease. We also seek prognostic markers that can predict rates of cognitive decline.More accurately diagnose and distinguish between dementia subtypes: Many types of dementia can present with similar clinical features, and patients often show overlapping pathologies. At present, it is challenging to distinguish between dementia subtypes and proteinopathies. Biomarkers that can distinguish between subtypes and stratify patients in clinical trials are of high priority.
Positron emission tomography (PET): These projects should focus on ligands for target engagement and pharmacodynamic measurements of novel and repurposed therapeutics. This RFP will support pharmacokinetics, safety, synthesis, and clinical development of novel PET ligands. The investigative team should include individuals with experience in developing PET ligands for human use.Magnetic resonance imaging (MRI): The proposed structural or functional approach should already have proof-of-concept data in human patients and be translatable for clinical use. Approaches that can measure novel targets and are significant improvements upon what is currently available in MR techniques are of higher priority.Magnetic resonance spectroscopy (MRS): The ability to detect specific molecules or proteins relevant to disease or a specific drug in development should be demonstrated in the preliminary data section of the application.
Cerebrospinal fluid (CSF) biomarkers can be a single analyte or panel of analytes; however, the proposed signature should have proof-of-concept data in human patient samples and the specific analyte combination should be well justified.
Functional activity measures applicable to this RFP include electroencephalogram (EEG), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS). Only highly novel techniques or analyses for EEG, MEG and TMS will be considered.
These proposals must meet the following criteria:
The proposed approach is an improvement on already existing functional measures used in clinical practice for diagnosing and monitoring dementias.The biomarker and its biological connection to the disease should be established and clearly described.Proof-of-concept data should be completed in human patients.
Other novel approaches: The biomarker should already be identified and validated in at least a small number of human samples.

Eligibility

Funding is open to researchers and clinicians worldwide at:Academic medical centers and universities or nonprofits. Industry partnerships are encouraged.Biotechnology companies. Funding is provided through mission-related investments that require return on investment based upon scientific and/or business milestones. Existing companies and new startups are both eligible.