NATIONAL CENTER FOR CANINE MODELS OF
DUCHENNE MUSCULAR DYSTROPHY (NCDMD)
Justification and Process for Application
The overarching goal of the National Center for Canine Models of Duchenne muscular dystrophy (NCDMD) is
to develop and sustain dog models of DMD and to provide high quality facilities and services in compliance
with GLP standards to support pre-investigational new drug (IND) applications and, thus, meet the increasing
demand to utilize golden retriever muscular dystrophy (GRMD) and other canine models of DMD in preclinical
studies required for human clinical trials. The essential services provided by the NCDMD will reduce costs of
assessing efficacy, ensure that results are consistent among investigators, and facilitate rapid translation to
clinical care. In addition, because the breeding colonies and core infrastructure of the NCDMD is supported
through a NINDS Co-operative Program in Translational Research (U-24) grant, fees charged to investigators
are reduced.
Proposals are sought from researchers who wish to conduct collaborative research projects that involve testing
of promising candidate therapeutics in dog models of DMD. The overall process for routing projects through
the NCDMD from original submission to the investigator-initiated investigational new drug (IND) application is
discussed in detail in the Overview section and summarized below:
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Investigators should contact NCDMD Director, Dr. Joe Kornegay, early in the process. Ultimate
submission of a subsidy application (below) is viewed as an iterative process.
Project application is reviewed and scored by the NCDMD Steering Committee (see committee
members under “About Us).” Key criteria to be evaluated include results from the mdx mouse,
availability of preliminary data from normal dogs (pharmacokinetics of the proposed compound,
etc), and the likelihood that the compound can be moved expeditiously to human trials. The
NCDMD Steering Committee will determine which therapeutic strategies will be pursued. Scientific
merit will be based on these three major criteria scored 1-5 points.
Approved projects will be initiated through the NCDMD Canine Muscular Dystrophy Facility (CMDF)
and the NCDMD cores (histology/molecular, physiology, and imaging) with oversight by the
NCDMD AQCO. Projects must complete sequential milestones to progress through the NCDMD.
These milestones will vary with individual projects but will generally involve demonstrating initial
success at the molecular or histological level before moving to physiological testing and imaging.
The NCMD will communicate regularly with the Project Investigator and Steering Committee.
Projects that do not achieve milestones will be terminated by the Steering Committee, with the
opportunity for appeal.
Results will be reviewed by the NCDMD AQCO and reported to the Project Investigator for initiation
of the IND application, if indicated.
NATIONAL CENTER FOR CANINE MODELS OF
DUCHENNE MUSCULAR DYSTROPHY (NCDMD)
Application for Subsidy
INVESTIGATOR (Attach Separate NIH Bio Form):
Name:
Degree(s):
Address:
Telephone Number:
FAX Number:
E-mail Address:
FUNDED OR PENDING GRANT TO SUPPORT PROPOSED RESEARCH (Note, while projects
supported through the NCDMD must ultimately have funding to support costs not covered by the
subsidy, a funded grant is not required. In fact, approval of a NCDMD subsidy could facilitate funding):
Grant Title:
Funding Agency:
Amount of Grant:
Support Period:
Begins (M/D/Y):
Requested Subsidy (Direct Costs Only): Initial Year:
(Attach Separate NIH Budget Pages for Subsidy)
Ends: (M/D/Y)
Total:
JUSTIFICATION FOR SUBSIDY (Complete Separate NIH Continuation Pages – Limit 5 Pages)
(See NCDMD Overview - Selection of projects for the NCDMD under Aim 2, Conduct Translational Research
Focused on Therapeutic Strategies). The NCDMD Steering Committee will determine which therapeutic strategies
will be subsidized. Criteria used to evaluate the scientific merit of applications will vary with the proposed method. In
general, merit will be based on three major criteria scored 1-5 points:
1.
Documentation of therapeutic benefit in the mdx mouse, as evidenced by systematic, published studies. All
therapeutic approaches will be considered. Treatments will generally fall into one of three major categories: (a)
molecular therapy wherein dystrophin expression will be the major outcome; (b) cellular therapy wherein sustained
implantation of transplanted cells with associated dystrophin expression will be the major outcome; and (c)
pharmacologic management wherein the outcome parameter(s) will vary with the particular intervention but should
include an intermediate measurement (biomarker) demonstrating that the compound is active at the proposed
mechanistic site. With any approach, multiple outcome parameters could apply. For assessment of skeletal muscle
function in mdx mice, preference will be given to investigators who have shown improvement in force generation
using an eccentric muscle contraction protocol. These studies will not be done through the NCDMD.
2.
Documentation of safety in normal dogs, to include the Pharmacokinetics/Biodistribution and Toxicological
profile of the compound/agent proposed. These studies could be done through the NCDMD. However, priority
would be given to projects in which these data were already available.
3.
Likelihood that the proposed therapeutic approach can be moved expeditiously into human clinical trials,
assuming that promising results are identified in a canine dystrophic model.
Check List for Appended Materials
NIH Bio Form for Principal Investigator
PDF of Funded Grant (if available)
IACUC Approval (Signature Page)
NIH Budget Pages for Requested Subsidy