Request for Proposals: Parkin Biology and Therapeutic Development Studies
The Michael J. Fox Foundation for Parkinson’s Research (MJFF) seeks to fund pre-clinical studies that investigate the biological function and therapeutic potential of Parkin protein. The ultimate goal is to identify therapeutic agents that alter the course of Parkinson’s disease.
There will be two separate ‘Tracks’ that may be pursued for support around Parkin as follows:
TRACK A – Biology
TRACK B – Therapeutic Development
Applicants may submit proposals to both Track A and Track B but it will need to do so by submitting separate applications that provide independent experimental designs for each. Applicants will be asked to justify the approach and to provide details of their study design.
Biological Studies
How will the proposed studies impact our understanding of Parkin:
As an enzyme
In cell biology
Therapeutic Development Studies
Current drug development stage with clear justification
Provide research operation plan, including feasibility, timelines, and all assays to be performed
Provide a clear description of the properties of the lead compound(s)/biologic
Please ensure that you utilize the correct template upon submission.
DEADLINES
Informational Conference Call*: June 6, 2013, 12:00 p.m. EST
Pre-proposals Due: June 19, 2013, 6:00 p.m. EST
Full Application Invites Sent to Applicants: July 3, 2013
Full Applications Due (by invite only): August 14, 2013
Anticipated Award Announcement: October, 2013
Anticipated Funding: November, 2013
*MJFF will hold a 45-minute conference call at the time listed above to clarify and explain the goals of this funding initiative and answer applicant questions. To participate in the call and receive call-in details, please RSVP via email to conferencecalls@michaeljfox.org, reporting “Parkin 2013” in the subject of the email.
BACKGROUND AND RATIONALE
PD is a progressive neurodegenerative disease affecting nearly five million people worldwide, with significant prevalence growth expected due to an aging population. Current therapies are effective in addressing only the mild-to-moderate motor symptoms of the disease and have significant long-term side effects. There are few specific drugs available that target the numerous non-motor aspects of the disease or the underlying degenerative process.
Though most cases of PD are considered idiopathic, investigators are increasingly identifying genes linked to this disease. However, these monogenic variants account for only a small proportion of all PD cases. Research on genetically implicated targets and associated pathways has the potential to yield critical insight and the development of therapeutics that may impact sporadic PD patients as well.
Parkin (PARK2) was identified as a gene linked to autosomal recessive juvenile forms of PD. Since its original discovery, many mutations and deletions have been identified (1). Parkin gene encodes a multidomain protein that contains E3 ubiquitin ligase activity that plays a role in the regulation of numerous cellular activities including proteasomal degradation of substrates but also ubiquitin-mediated signaling (1). Parkin has also been suggested to function as a transcription factor, regulating p53 expression (2) independent of its ligase activity.
Thus there is the distinct possibility that promoting Parkin activation may have implications in ameliorating cellular signaling pathways as well as regulation of degradation pathways. Given recent advances in understanding Parkin structure, investigators now have at hand a tangible means of optimizing small-molecule development through structure-based drug design.
PURPOSE
The goal of the Parkin Biology & Therapeutic Development Program is to support:
1. Studies that provide critical insight into the biological mechanisms of Parkin function
2. Discovery and development of therapeutic agents that have the potential to modulate Parkin function in a manner that will alter the course of Parkinson’s disease progression.
Although most traditional therapeutics targeting modulation of enzymatic activity involve small-molecule development, MJFF is also open to alternative strategies, including gene therapy and biological (non-pharmaceutical) approaches that can have significant impact on Parkin activity. Moreover, as drug targets may be shared among multiple diseases and/or drugs may hit multiple disease targets, MJFF is also interested in drug repositioning of molecules for Parkin that have been approved or shown to be clinically safe for other indications.
Proposals may seek support of key steps along the entire therapeutic pipeline, including:
High-throughput screening
Primary assay development and validation
IC50 generation/validation in second primary assay and chemistry support for hit ranking and clustering
Hit-to Lead and Lead Optimization
Chemistry support
In vitro and in vivo PK, PK/PD relationships, toxicity studies
Applicants are asked to develop a clear plan, including major ‘go/no go’ decision milestones, for moving a therapeutic strategy toward ultimate clinical utility in people with PD. Investigators new to PD research are encouraged to collaborate with experienced PD scientists and/or companies to ensure the greatest chance for success.
REFERENCES
1.Cell Mol Life Sci (2012) 69:3053-3067
2.Neurodegenerative Dis 2012 10:49-51
FUNDS AVAILABLE
MJFF will commit up to $2 million to the Parkin Biology & Therapeutic Development Program with the intention to support multiple awards. The requested support should be commensurate with the stage of development and work proposed.
Investigators applying to Track A (Biology) may request up to $125,000 in support (inclusive of indirect costs) for up to one year.
For those applying to Track B (Therapeutic Development) there is no set budget limit for proposals and applicants may request up to two years of funding for preclinical development.
No more than 25% (Academic institutions) or 10% (for-profit institutions) of direct costs may go to indirect costs. Please see the program instructions, Administrative Guidelines and our FAQ on MJFF indirect cost policy for details. MJFF reserves the right to reduce the duration and budget based on its review and final funding decision.
Eligibility Requirements
Applications may be submitted by:
U.S. and non-U.S. biotechnology/pharmaceutical companies or other for-profit entities, either publicly or privately held,
U.S. and non-U.S. entities, 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.
As therapeutic programs may require many kinds of expertise, MJFF encourages industry and academic collaborations when appropriate. Given the significant coordination and leadership necessary for this program, post-doctoral fellows are NOT eligible to apply as PIs.
