Target Validation Program
INSTRUCTIONS FOR SUBMITTING A PROJECT SUMMARY
Part of our annual Edmond J. Safra Core Programs for PD Research, the Target Validation program supports work seeking to determine if manipulating a novel biological target has impact in a Parkinson’s disease (PD)-relevant animal model—an essential early step to the development of potentially promising therapies.
Spring 2014 Review Cycle
- Informational Conference Call*: September 18, 2013 at 12pm US ET
- Pre-Proposals Due: October 30, 2013 – 6pm US ET
- Full Proposal Invitations: November 20, 2013
- Full Proposals Due (by invite only): January 15, 2014– 6pm US ET
- Anticipated Award Announcement: March 2014
- Anticipated Funding: April 2014
Fall 2014 Review Cycle
- Informational Conference Call*: March 26, 2014 at 12pm US ET
- Pre-proposals Due: May 28, 2014 – 6pm US ET
- Full Proposal Invitations: June 18, 2014
- Full Proposals Due (by invite only): August 6, 2014 – 6pm US ET
- Anticipated Award Announcement: October 2014
- Anticipated Funding: November 2014
*MJFF will hold a 45-minute conference call on the dates and times 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 firstname.lastname@example.org.
BACKGROUND AND RATIONALE
Research into the etiology and pathophysiology of PD has identified an increasing number of genetic and cellular targets where therapeutic intervention could benefit people with PD, including:
- Epidemiological studies that have identified both protective and risk factors for PD.
- Genetic studies that have implicated candidate genes whose protein products may underlie PD pathogenesis.
- Biochemical studies from cellular and whole organism model systems that point to biological pathways important in PD etiology and pathogenesis, as well as examination of cell death and trophic factor signaling pathways that have pointed to potential protective targets.
- Emerging understanding of dopamine neuronal development and maintenance in adulthood that has provided potential targets to restore/protect dopaminergic function in PD patients.
- Improved understanding of the neurochemistry and neurophysiology of the basal ganglia and related neuronal circuits that have suggested ways to alter neuronal function that could help treat motor and non-motor symptoms of PD not addressed by current therapeutics.
- Better understanding of the physiological and molecular pathways underlying treatment-induced complications that have revealed potential targets for interventions to ameliorate these troubling side effects.
Although such discoveries provide great insight into the pathobiology of PD, translation into therapeutic interventions requires additional applied work. Target validation studies determine whether manipulating the availability or function of a biological target can beneficially impact a disease-relevant pathway. Such data, along with information about the target‘s location in relevant disease tissues and evidence supporting a link between the target and human PD, can all make a strong case for further therapeutic development.
Pharmaceutical and biotech companies, who are generally the best suited to carry promising therapies forward into the clinic, must carefully weigh the evidence and risk-benefit of a target before deploying significant resources. MJFF believes that promoting critical target validation studies within academic and industry laboratories can help ‘de-risk‘ these investments and ultimately accelerate the creation of improved therapies for people with PD.
The Target Validation program supports work to determine whether manipulation of a defined biological target provides a disease-relevant beneficial outcome in a whole animal, mammalian model of PD. MJFF does not have any pre-conceived preferences for particular targets submitted to the Target Validation program. However, we recommend applicants consider the following:
- The target should be clearly defined, such as:
- A specific gene
- A structural/functional feature of a protein (e.g., its enzymatic activity, protein conformation or ability to interact with other proteins)
- Proposals seeking to manipulate global pathways without a clear target are not encouraged
- Applicants may propose a variety of methods to manipulate a target, including but not limited to:
- Use of pharmacological tools
- Supporting data/explanation of the proposed pharmacological tool must be addressed in the body of the proposal. Parameters that should be discussed include:
- Selectivity for the target of interest
- Pharmacokinetic/Pharmacodynamic measures that have been/will be assessed
- Measures of target engagement
- Use of biologic strategies such as:
- Small molecules
- Viral vector-mediated gene delivery, etc.
In Vivo Models
- Applicants may also propose use of models appropriate for the target proposed including:
- Toxin models
- Previously established genetically engineered animal models including:
- Knockout models where the target/gene of interest is deleted
- Transgenic models whereby the target/gene of interest is over-expressed
- Investigators should proposed to examine PD-relevant features or sensitivity to PD-associated factors during the course of their studies
- Proposals may include intermediate tests using in vitro, ex vivo and/or model organisms (e.g., Drosophila, C. elegans) to optimize the ideal target manipulation strategy
- These proposals must ultimately include within the grant funding period an evaluation of the target manipulation in a whole-animal mammalian model of PD
Note: The following types of proposals are not appropriate for the Target Validation program:
- Proposals focused on new target identification and proposals testing cellular transplantation approaches.
- Proposals seeking to generate new genetic (knockin, knockout, transgenic) models
- Investigators seeking guidance to develop new models around their target are encouraged to contact email@example.com
Applicants seeking support for therapeutic development should submit to the Therapeutic Pipeline Program or contact MJFF research staff for guidance.
MJFF will commit up to $10 million to the Edmond J. Safra Core Programs for PD Research with the intention to support multiple awards. The Target Validation program supports two-year grants up to $250,000 total costs inclusive of both direct and indirect costs. The total annual direct costs cannot exceed $100,000. No more than 25% (Academic institutions) or 10% (for-profit organizations) of the direct costs may go to indirect costs. Please see the program instructions, Administrative Guidelines and our FAQ on MJFF indirect cost policy for details.
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.
Post-doctoral fellows are NOT eligible to apply as Principal Investigators to the Target Validation program.
Please refer to our Administrative Guidelines.Note that any information listed above will supersede information contained in our general MJFF administrative guidelines.
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