Seed Amplification Assay Innovation Program

Overview

Objective

This program seeks to advance the development of high-performance, quantitative alpha-synuclein seed amplification assays (aSyn-SAAs), addressing the critical need for less invasive, highly sensitive, and quantitative biomarkers in Parkinson’s disease (PD) clinical trials.

Research must address one or both critical gaps to integrate aSyn-SAA into clinical practice and therapeutic development:

* Current aSyn-SAAs provide binary (positive/negative) results rather than quantitative assessment, precluding their use for monitoring disease progression and evaluating treatment effects.  
* The invasiveness of spinal tap limits its utility in routine clinical practice, can delay or deter subject recruitment in clinical trials, has poor accessibility/acceptance in some geographies, and is not amendable to request repeated sampling.

Research must aim to overcome these challenges through the development of quantitative aSyn-SAA in cerebral spinal fluid (CSF) and in less invasive methods around biofluids or tissue.

Eligibility

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Application Details

Spring 2025 Request for Applications
Seed Amplification Assay Innovation Program
BACKGROUND
Parkinson’s disease (PD) affects nearly 1 million people in the US and over 6 million worldwide,
with these numbers expected to rise in the coming decades. PD is highly heterogeneous,
meaning individuals experience a wide array of motor and non-motor symptoms, which depend
on disease severity and duration. While our understanding of PD and its causes is improving,
many questions remain. Currently, no drugs exist that can alter the progression of PD, and
available treatments focus only on alleviating symptoms, providing limited relief while often
coming with complications and side effects.
The Michael J. Fox Foundation (MJFF) funds research to better define, measure, and treat
Parkinson’s disease as well as critical tools and other resources to advance that research. MJFF’s
funding to develop, analytically qualify and validate alpha-synuclein seed amplification assays
(aSyn-SAA) in cerebrospinal fluid (CSF) contributed to the recent Letter of Support by the FDA
toward the use of CSF aSyn-SAA for patient enrichment in therapeutic trials. Specifically, CSF
aSyn-SAA has >90% sensitivity and specificity for identifying recently diagnosed sporadic PD
cases. Importantly, CSF aSyn-SAA can detect neuronal alpha-synucleinopathy prior to clinical
diagnosis, thereby providing an important anchor for the biology-founded Neuronal Synuclein
Disease Integrated Staging System (NSD-ISS). However, two critical gaps need to be addressed
to integrate aSyn-SAA into clinical practice and therapeutic development:
1. Current aSyn-SAAs provide binary (positive/negative) results, rather than quantitative
assessment. This precludes their use for monitoring disease progression and evaluating
treatment effects.
2. The invasiveness of spinal taps limits its utility in routine clinical practice, can delay or
deter subject recruitment in clinical trials, has poor accessibility/acceptance in some
geographies and is not amenable to frequent repeated sampling.
The purpose of this Request for Applications (RFA) is to overcome these obstacles by funding
projects that directly address these challenges through the development of quantitative aSyn-
SAA in CSF as well as in more accessible biofluids or tissues. Applicants may seek to address one
or both challenges in a single application towards the goal of enabling feasible, efficient and
quantitative measures of aSyn in SAA for clinical trials.

PROGRAM GOAL
The SAA Innovation Program seeks to advance the development of high performance,
quantitative seed amplification assays for aSyn, addressing the critical need for less invasive,
highly sensitive and quantitative biomarkers in clinical trials. MJFF’s priorities for this RFA are
aligned with the current state of the field as described below:
• Existing aSyn-SAA in CSF exhibits extremely high sensitivity and specificity for neuronal
synuclein disease and can identify individuals who are at high risk for developing PD and
Dementia with Lewy Bodies (DLB) years before symptom onset. Nonetheless, CSF-SAA
cannot be used as a biomarker of disease progression or pharmacodynamic/therapeutic
response without technical advances that enable robust quantitation. Proposals
addressing this critical need that can advance the quantitation of SAA in any biological
matrix (including CSF) will be given top priority.
• aSyn-SAA in other biofluids and tissues have the potential to augment CSF assays but
require further analytical development and validation. While studies have demonstrated
feasibility in matrices such as skin, blood, tears, saliva and olfactory mucosa, the field still
grapples with issues of sensitivity, specificity and reproducibility. Pre-analytical variables,
such as optimal methods for sample collection, storage and processing are poorly
understood and vary between studies. These gaps in standardization hinder scalability
and clinical applicability of SAA in peripheral matrices, making it critical to address these
challenges to fully realize the potential of these less-invasive matrices. SAAs in peripheral
matrices are also not yet quantitative.
MJFF will prioritize proposals that:
• Develop high-performance, quantitative seed amplification assays for alpha-synuclein.
• Tackle challenges in sensitivity, specificity and reproducibility of SAA in peripheral
biofluids and tissues.
MJFF will NOT consider proposals focused on:
• CSF SAA that is strictly binary
• Semi-quantitative SAA in CSF that is based on the analysis of serial endpoint dilutions
• Immunoassays to measure post-translationally modified forms of aSyn (e.g. pS129-aSyn)
or ‘total’ aSyn
• Other non-SAA techniques
• aSyn imaging proposals
• SAA for misfolded proteins other than aSyn – Please note that although SAA for other
proteins such as TDP-43 and tau are out of scope for this program, you may reach out to
us at grants@michaeljfox.org to discuss future opportunities.
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FUNDING AVAILABLE
Duration: 6 to 24 months
Award Amount: Up to $1,000,000. Requested support should be commensurate with the work
proposed.
These budgets include direct and indirect costs. For academic and for-profit institutions, no
more than 15%, respectively, may go to indirect costs. Additional details about MJFF's indirect
cost policy can be found in the Application Guidelines and FAQ.
DEADLINES & REVIEW SCHEDULE
• Full Proposals Due: January 30, 2025, 5 p.m. US ET
• Anticipated Award Announcement: April 2025
• Anticipated Funding: June-September 2025
Applicants are encouraged to apply early to allow adequate time to correct errors found during the
submission process.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by researchers or clinicians in:
• U.S. and non-U.S. biotechnology/pharmaceutical companies, or other publicly or
privately held for-profit entities; and
• U.S. and non-U.S. public and private non-profit entities, such as universities, colleges,
hospitals, laboratories, units of state and local governments and eligible agencies of the
federal government.
• Post-doctoral fellows are NOT eligible to apply as co-investigators.
BIOSAMPLE REQUESTS
Investigators are encouraged to leverage existing tissue and biosample resources if possible.
While priority will be given to researchers with access to existing biobanks, studies requesting
access to biosamples available through MJFF-sponsored biospecimen are eligible to, through
this initiative. In these cases, please respond to the relevant biosample questions in the proposal
template document. Please note that access to samples will be reviewed in parallel to funding
requests by the committees overseeing the biospecimen collection(s) requested. To review
MJFF’s available biosample collections, please consult the MJFF biorepository and biorepository
inventory catalogue.
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DIVERSITY, EQUITY AND INCLUSION (DEI)
In pursuit of our mission to accelerate the development of better treatments and a cure for
Parkinson’s disease, MJFF aims to support a rigorous research agenda reflecting a wide and
diverse range of perspectives on Parkinson’s disease and carried out in diverse populations.
Diversity may refer to characteristics including, but not limited to, race, religion, ethnicity, sex,
gender identity, sexual orientation, socioeconomic circumstance, nationality, geographic
background, ability and disability, political ideology and age. Parkinson’s is a complex problem;
the more angles from which we attack, the greater the chances of finding innovative scientific
solutions to benefit everyone living with the disease. As such:
• The Foundation encourages applications from diverse investigators representing groups
historically underrepresented in the research enterprise.
• Because research shows that diverse teams outperform homogeneous ones, we urge
applicants to share information about the composition of the team that will carry out the
funded work.
ADDITIONAL INFORMATION
The Application Guidelines provide general guidance on applying for funding from MJFF, though
the RFA always supersedes information contained in the Application Guidelines.
MJFF holds an open access publication policy requiring articles resulting from MJFF-funded work
to be published in a preprint repository, then in an open access forum with free and immediate
readership rights. Grantees will be asked to provide proof of compliance with this policy, and
future funding will be contingent upon adherence.
MJFF requires that the Principal Investigator be the primary applicant (i.e., the person who
initiates and takes primary responsibility for the application). All application-related
correspondence will be sent to the Principal Investigator.
For questions about the application process or project suitability for this call for applications,
please email grants@michaeljfox.org .
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