Announcing: August 2011 Research Update from Dr. Hal Dietz on
Vascular EDS Research
In 2010, Ehlers Danlos Syndrome Network C.A.R.E.S. Foundation funded our first EDS research project
on vascular EDS. Dr. Hal Dietz, Victor A. McKusick Professor of Medicine and Genetics, Institute of
Genetic Medicine Investigator, Howard Hughes Medical Institute, Johns Hopkins University School of
Medicine is committed to vascular EDS and this important research.
Last year, Dr. Dietz explained the purpose of his research to EDS Network CARES prior to our
funding of his project.
"Until very recently, the prospects for developing a meaningful therapeutic strategy for vascular
EDS have appeared dismal. The prevailing view has been that the abnormal type III collagen leads
to a deficiency in the amount of normal type III collagen that the body has to use, and thus results
in an inherent weakness of the tissue. Yet by taking the undeniable parallels seen in two other
connective tissue disorders, Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS), it is
believed that the same model––illustrating a failed matrix regulation of Transforming Growth
Factor Beta––may also be in play for vEDS. In fact, there is currently a clinical trial underway for
treatment of MFS.
This observation supports a very important question: Does vascular EDS simply reflect loss of
tissue integrity imposed by a deficiency of type III collagen or might altered TGF signaling also be
involved in this condition? If so, does the research being done for MFS show similar promise in the
treatment of vascular EDS?
The results to this question were presented this fall at the 2008 American Society of Human
Genetics Conference in an abstract entitled Altered Cytokine Signaling in Vascular Ehlers Danlos
Syndrome (vEDS). This is the first published document presented that suggests that there is an
increased signaling of the TGF-beta family seen in vEDS fibroblasts.
The results of this paper indicate the need for further investigation in a vEDS mouse model in
which a mutated copy of the COL3A1 gene is present. The development of this mouse model will
allow researchers to explore the usefulness of medications that regulate the TGF-beta family.
Additionally this research may enable the understanding of the mechanism involved in not only
vEDS, but potentially all other types of Ehlers-Danlos syndrome and other disorders in which the
collagen proteins are affected. "
August 2011 Vascular Research
An Update from Dr. Hal Dietz
"We remain very committed to vascular EDS work, including the creation of a bona fide mouse model of
disease. While I expected this to proceed more quickly, the type III collagen gene has proven very
challenging due to a very complex and repetitive gene structure. This has greatly complicated every step in
the process. I think that all of the hard work is now behind us (but cannot exclude additional obstacles in
the future).
What I can say now with confidence is that we have now succeeded in introducing a common and severe
vEDS mutation into mouse embryonic stem cells. If all goes as planned, I would hope to have mice with
this mutation in their testes or ovaries by the end of the summer, and mice with the mutation in every cell
of their body by fall. We have all of the reagents and protocols ready to initiate treatment trials.
We have received funding from the US and Canadian Foundations to support this work. This has helped
to pay the salary of a very talented graduate student who is committed to this work (Juan Calderone). The
process of expanding the mouse line and performing trials will be quite expensive. The funds needed to
perform similar work for the Marfan mouse model was about $50,000 per year for 2 years. This would be
for a single trial and we hope that many would be occurring in parallel from other sources."
Hal Dietz
Victor A. McKusick Professor of Medicine and Genetics
Institute of Genetic Medicine
Investigator, Howard Hughes Medical Institute
Johns Hopkins University School of Medicine