These are just some of the researchers (a.k.a. heroes) who are hard at work on projects that could greatly impact families with EDS and other related connective tissue disorders. If you haven’t already figured it out, it’s up to each of us to stay informed of the latest information and make sure we get it into the hands of those taking care of us or our loved ones. If you know of a project or researcher you think should be added please let me know. I’ll try to keep this updated as new developments arise. April, 2010
Dr. Hal Dietz, Johns Hopkins
The following post is a copy of a letter written by Dr. Hal Dietz at Johns Hopkins University in MD regarding the very promising research currently underway for vascular Ehlers-Danlos syndrome. At the urging of the Ehlers-Danlos Network C.A.R.E.S., Dr. Dietz agreed to explore the possibilities of a new treatment already working in a disorder very similar to VEDS. His letter describes the struggle of these patients, the hope of this study, and the amazing potential that could be just a few years away.
Vascular Ehlers-Danlos syndrome (or vascular EDS) is a disorder of the body’s connective tissue – the material between the cells that give the tissues form and strength. In vascular EDS the body lacks sufficient type III collagen, a molecule that contributes to the strength of the skin, intestines, uterus, and most importantly, the blood vessels. People with vascular EDS live with the knowledge that they will die from this condition at an age ranging from childhood to young adulthood. They are also told that there are no effective treatments. There are no medications that are known to strengthen the tissues or delay blood vessel rupture. Attempts at surgical repair are often delayed unless there is confidence that the patient will die within hours if nothing is tried. This is because the tissues are so weak that they often simply fall apart during surgery – akin to trying to sew together wet tissue paper. Of all the conditions that I care for, I hate this one the most.
It not only drastically shortens the length of life, but also robs people of any meaningful sense of hope and quality of life – always anticipating that the shoe will drop at any moment. Indeed, all too often children with vascular EDS lose any sense of ambition and purpose despite truly remarkable talents and potential. To their mind, “Why bother?”.
Fortunately, there is now strong reason for hope. During the study of related connective tissue disorders, specifically conditions called Marfan syndrome and Loeys-Dietz syndrome, we learned that many issues, including blood vessel enlargement and rupture, do not simply reflect an inherent weakness of the tissues due to a deficiency of the body’s glue. Instead, the deficiency of a connective tissue protein, as in vascular Ehlers-Danlos syndrome, triggers an increase in a specific cellular signaling pathway, causing the cells to behave abnormally and to release enzymes that break down the tissues. We have early evidence that the same process is at work in vascular EDS. In mouse models of Marfan syndrome we have shown that a medication that is widely used for other purposes can blunt abnormal cellular behaviors and prevent blood vessel enlargement and rupture, leading to a fully normal lifespan. This medication is now in clinical trial in children with Marfan syndrome. It is now our goal and intention to make mouse models of vascular EDS in order to learn more about the condition and to test this and other therapies.
If someone had suggested 5 years ago that a pill might be able to treat a connective tissue disorder, I would have considered them crazy. Given recent breakthroughs and sufficient resources for further research, I will be shocked if a revolutionary new treatment for vascular EDS is not in general use within 5 years. I have already begun to share this sense of optimism with children with vascular EDS. Our job is to bring this goal to fruition. Their job is to begin dreaming big.
While ambitious, the proposed work directly parallels our prior initiatives for Marfan syndrome and Loeys-Dietz syndrome. Realistically, the work could start with an investment of $100,000. This would cover initial costs for the development of a mouse model and the recruitment of a research scientist fully committed to this work. Expansion of the mouse colony and completion of both mechanistic and treatment studies would require about $200,000 per year for three to four years.
Dr. Nazli McDonnell
National Institutes of Health (NIH)
Dr. McDonnell’s research is focused on clinical and molecular investigations of hereditary disorders of connective tissue (HDCT). The disorders of interest are Ehlers-Danlos syndrome (EDS), Marfan syndrome, Stickler syndrome, hereditary aneurysm syndromes and fibromuscular dysplasia (FMD).*
In collaboration with Dr. Mark Talan’s group, she is working with a mouse model of VEDS to discover and assess treatment strategies for VEDS. Other investigations include the role of tenascin X (TNXB) mutations and deletions in Hypermobile EDS and in patients with Congenital Adrenal Hyperplasia (in collaboration with Dr. Debbie Merke, NICHD), the study of genotype/phenotype correlations in Stickler Syndrome (with Dr. Ala-Kokko), discovery of new causative genes for familial aneurysm syndromes and in families with HDCT where no mutation in the known genes such as COL5A1, COL5A2, COL2A1, COL11A1, COL3A1, TGFBR1, TGFBR2 or fibrillin has been identified (with Dr. Andrew Singleton).*
* Information obtained from: http://www.grc.nia.nih.gov/branches/lci/nmcdonnell.htm
Dr. McDonnell’s study is currently accepting new applicants. I’m hoping to enroll my son this summer, and have several friends who are already participating.
I can’t emphasize enough the benefits of being a part of something like this. For my friends, Dr. Naz has been a life-saving resource when they’ve had medical crises arise. She and her staff have been able to offer critical guidance to local doctors when patients were in serious if not life-threatening situations.
Even though this study is still in process and hasn’t reached all of it’s formal conclusions, the insights being gained are priceless. If you or a family member are living with any form of Ehlers-Danlos Syndrome, Marfan Syndrome, Stickler Syndrome, Loeys-Dietz Syndrome, Familial Aneurysms, or a related connective tissue disease, PLEASE check this out.
Click on Dr. Naz’s picture to go to the NIH site for applications to the study.