# NHLBI MAINTENANCE OF CANINE MODELS OF HUMAN BLEEDING DISORDERS

> **NIH NIH N01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $1,422,512

## Abstract

The purpose of this N01 contract is to produce and maintain the following dog models of inherited bleeding disorders for independent and collaborative scientific investigations: hemophilia A and hemophilia B with and without inhibitory antibodies to FVIII and FIX, respectively; von Willebrand disease (VWD); FVII-deficiency; and Glanzmann’s Thrombasthenia. Beginning in 1947 with an R01 from NIH/NHLBI, Dr. Kenneth M. Brinkhous and colleagues identified these dogs and demonstrated that (1) they mirror the severe bleeder phenotype present in the respective human disorder and (2) have a strong predictive accuracy for successful translational research.1 In 1999, the reviewers of Dr. Brinkhous’ R01 judged these dogs to be an important national resource that should be made available to the research community and NHLBI support was transitioned to an R24 (T.C. Nichols, PI). We are now applying to transition support of this colony to this N01 contract. Since 1999, we have produced bleeder and normal dogs that have been used in collaborations with over 30 teams of investigators, most with NHLBI support, and the work has been reported in over 95 peer-reviewed publications1-96 and Conference Proceedings97-102, several of which were selected for editorial review. Recently, vectors used in at least 5 human gene therapy trials for hemophilia B and 2 for hemophilia A, six new recombinant anti-hemophilic proteins, and recombinant von Willebrand factor (VWF)and IL-1120 for VWD have been tested in these dogs prior to clinical trials. In all cases, the results predicted safety, efficacy, and drug dose responses. The primary benefits of these animals have been to accelerate translatable discovery science in coagulation and hemostasis research and to produce the scientific basis for the safe and efficacious introduction of novel therapeutics into clinical practice.
Considerable progress has been made over the past 7 decades in understanding the basic science of blood coagulation and hemostasis and in developing new clinical approaches to inherited bleeding disorders. Yet, there are persistent limitations in therapeutic options for people with VWD and hemophilia, especially those with inhibitors.

## Key facts

- **NIH application ID:** 10499861
- **Project number:** 75N92019D00041-P00002-759201900074-1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** TIMOTHY NICHOLS
- **Activity code:** N01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,422,512
- **Award type:** —
- **Project period:** 2019-09-20 → 2022-09-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499861

## Citation

> US National Institutes of Health, RePORTER application 10499861, NHLBI MAINTENANCE OF CANINE MODELS OF HUMAN BLEEDING DISORDERS (75N92019D00041-P00002-759201900074-1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10499861. Licensed CC0.

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