MJFF Targets to Therapies: Mitochondrial Target Validation

International funding to speed up the validation of high-priority mitochondrial mechanisms and targets, while addressing major gaps that are hindering the development of effective therapies for Parkinson’s disease.

Established in 2000, the Michael J Fox Foundation (MJFF) was set up to find a cure for Parkinson’s disease (PD) and ensure the development of improved therapies.

The purpose of the MJFF Targets to Therapies (T2T): Mitochondrial Target Validation Request for Applications (RFA) is to accelerate validation of high-priority mitochondrial mechanisms and targets (USP30 (and other related de-ubiquitinating enzymes eg USP15), CACNA1D (CaV1.3), NFE2L2 (Nrf2) and PARK7 (DJ-1)) and address critical gaps limiting therapeutic progress in PD. To this end, MJFF believes that promoting coordinated, target-centric and pathway-informed studies will provide the mechanistic and translational evidence needed to advance these targets toward therapeutic development.

The T2T Program seeks to build a robust evidence base for mitochondrial and/or neuroprotective targets with high potential relevance to PD. Funding will support projects to clarify human relevance, define mechanism in PD-relevant contexts, establish target engagement, or develop enabling tools and assays. Support is available for:

• Target modulation in cell and animal models to determine efficacy on PD phenotypes.
• Generate evidence linking target biology to PD patient samples.
• Clarifying the therapeutic mechanism of action.
• Identify and test biomarkers to aid preclinical therapeutic validation and patient stratification.
• Biological safety through animal model characterisation.

When considering proposals, priority will be given to those that: directly address known target gaps (eg human modulation, biomarker linkage, mechanism in alpha-synuclein biology and related PD pathology); and generate reproducible, translatable data that advances the target towards a therapeutic decision point.