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U.S. Department of Health and Human Services

About FDA

Linkages between Gene and Protein Expression and Chemical Exposures Measures

Description: Determine the impact of canine MDR-1 mutations on therapeutic effectiveness and adverse reactions to veterinary drugs. These studies will improve CVM's ability to evaluate the safety of new animal drugs and create new models for investigation of possible adverse events. The pharmacogenomics data of a new drug and the potential for toxicity will improve the agency's ability to predict safety and effectiveness of canine new drugs.

Definition: This project showcases the Office of Research's ability to connect several universally accepted experimental methodologies, from genetic analysis to computational modeling to traditional animal research, in order to discover therapeutically useful information. The ultimate outcome of this research will enhance CVM's ability to evaluate the safety and effectiveness of new animal drugs. Furthermore, CVM will be able to predict and hone in on adverse events more accurately. (1)

Briefing Status: DELAYED

Prior Briefing Status: ON TRACK

Milestone DescriptionMilestone DateMilestone StatusMilestone Completion Date

1. Create genetically modified rodent expressing canine MDR-1 gene for evaluation as a model for pre-clinical testing of new veterinary pharmaceuticals

3/30/2010

Completed 3/30/2010

2. Genetically characterize MDR-1 gene in normal and affected collies, including response to drug treatments

4/30/2010

Completed 4/30/2010

3. Initiation of genetically modified rodent in-house breeding program

9/30/2010

Completed 9/30/2010

4. Initiation of validation study of genetically MDR-1 rodent model

10/30/2010

Completed 9/30/2010

5. Initiation of Collie Single Nucleotide Polymorphism (SNP) study analysis of MDR-1 gene in normal and affected collies

4/30/2011

Completed 4/30/2011

6. Analyze pharmacokinetics of two model drugs in normal and affected collies

9/30/2011

(11/30/2011)

(5/30/2012)

(12/30/2012)

(5/30/2013)

(12/31/2014)

Delayed

7. Create a genetically modified rodent homozygous for the normal canine MDR-1 gene, for evaluating possible adverse events associated with veterinary pharmaceuticals

12/30/2011

Completed 12/30/2011

8. Publish manuscript for mouse model

12/30/2011

Completed 12/30/2011

9. Initiate cross-breeding of the two new rodent models to generate offspring that are heterozygous for the mutant canine MDR-1 gene

1/30/2012

Completed 1/30/2012

10. Validate a genetically modified mouse homozygous for the normal canine MDR-1 gene, for evaluating possible adverse events associated with veterinary pharmaceutical (2)

6/30/2012

(12/30/2012)

(5/30/2013)

Milestone Terminated

11. Provide CVM reviewers with a mouse rodent that may be usd to replace the collies in safety assessments of new avermectin-class drugs for safety studies of other potential MDR-1 substrates (2)

12/30/2012

(12/30/2013)

Milestone Terminated

Footnotes

  • (1) The dates in italics under the milestone due dates are modified due dates which had to be updated due to real-time delays. The milestone status reflects the modified dates.
  • (2) Milestone has been terminated due to a shift of regulatory need for the mouse model.

Key Projects Legend

Milestone StatusDefinition
Not Yet StartedWork for specific milestone has not yet been started.
CompletedMilestone and/or overall project is completed.
On TrackMilestone - On track for completion by milestone deadline. Quarter status - Project is on track for completion based on overall milestone status.
On HoldMilestone - On hold, but deadline for completion has not passed. Quarter status - Project is on hold, based on overall milestone status.
DelayedMilestone - Delayed as it has not been completed and deadline has passed. Quarter status - Project is delayed based on overall milestone status.

Glossary

MDR-1

Multidrug Resistance Protein 1

SNP

genetic variation in a DNA sequence that occurs when a single nucleotide, or functional unit of DNA - a sugar group, is altered

pharmacokinetics

study of how the body processes a drug

Note: The data provided on this website is produced on an ongoing basis for performance management purposes and is subject to change due to updates of preliminary estimates, corrections, or other reasons. In addition, FDA may change the type or amount of data provided on this website at any time. Information marked as "Completed" may include measures and/or key projects for which activities are ongoing but no longer tracked as part of FDA-TRACK.