Vascular Ehlers-Danlos Syndrome (vEDS)

Vascular Ehlers-Danlos Syndrome (vEDS, previously known as EDS Type IV or EDS IV) is a subtype of Ehlers-Danlos Syndrome (EDS), a disorder of collagen production. Collagen is the main protein in connective tissue such as skin, bones, blood vessels, and many other organs and tissues.

Unlike other subtypes of EDS, people with vEDS often do not have the typical symptoms of EDS, which include skin hyperextensibility (skin that is easily stretched) and hypermobility of the joints (unusually large joint range of motion). Because of the lack of other symptoms associated with EDS, the first symptom a person with vEDS may experience is often related to a catastrophic complication, such as colonic perforation, when the tissue of the colon tears, or an arterial rupture, when the wall of an artery tears.¹

Vascular EDS is considered the most severe EDS subtype. The average lifespan is 50 years, with 70% of people with vEDS experiencing a major complication by the age of 30 years. There are approximately 2,000 people in the U.S. diagnosed with vEDS, though experts estimate as many as 5,000 people may be affected.¹

Vascular EDS should be suspected in the presence of the following major symptoms:²

• Characteristic facial features (thin lips, narrow nose, undersized jaw, protruding eyes)
• Easy bruising
• Thin skin with visible veins (especially on the chest or abdomen)
• Rupture or tearing of the arteries, intestines or uterus
• Family history of vEDS

Other less obvious symptoms that may also help raise suspicion of vEDS include:²

• Acrogeria (an aged appearance, especially of the hands and feet)
• Carotid-cavernous sinus arteriovenous fistula (an abnormal connection between an artery in the neck and a set of veins behind the eye)
• Joint hypermobility
• Rupture of muscles or tendons
• Early-onset varicose veins
• Collapsed lung (with possible buildup of blood in the chest cavity)
• Chronic joint dislocations
• Dislocated hips or clubfoot (in infants born with the disorder)
• Receding gums

Clinical suspicion of vEDS is confirmed through genetic testing of COL3A1 and/or biochemical analysis of fibroblasts, the cells that produce collagen, as a means of detecting abnormalities in type III collagen.¹

There is currently no approved treatment option for vEDS. In 2015, the U.S. Food and Drug Administration (FDA) granted Edsivo™ (celiprolol) orphan drug designation for the potential treatment of vEDS.

» For up-to-date information about ACER-001 for UCD, subscribe to receive email updates here.

 

Edsivo™ (celiprolol) for vEDS

Edsivo™ (celiprolol) is being studied for the treatment of vascular Ehlers-Danlos Syndrome, or vEDS, in the United States. Celiprolol is a chemical entity originally developed to treat hypertension.³ Celiprolol is believed to provide clinical benefit for people with vEDS by promoting normal collagen synthesis in the blood vessels, and by shifting the pressure load away from the vessels most prone to dissection and rupture.⁴ Although it can also be used to treat mild to moderate hypertension (high blood pressure), celiprolol does not lower blood pressure in people with normal blood pressure.³

In a study of people with vEDS in eight centers in France and one in Belgium, 53 people with vEDS were randomized to either a treatment group (25 people) or non-treated control group (28 people). Those in the treatment group received up to 400 mg of celiprolol per day (200 mg by mouth twice daily).  Twenty percent of people in the celiprolol-treated group had an arterial event (either rupture or dissection) versus fifty percent of the non-treated control group. This demonstrates a significant reduction in risk for arterial events in the group being treated when compared to the non-treated control group. As well, very few adverse events or side effects of treatment were reported; two people reported fatigue and one person discontinued treatment due to extreme fatigue.⁵

In 2015, the U.S. Food and Drug Administration (FDA) granted Edsivo™ (celiprolol) orphan drug designation for the potential treatment of vEDS. Orphan drug designation is provided to drugs and biologics that are defined as intended for the safe and effective treatment, diagnosis, or prevention of rare diseases and disorders that affect fewer than 200,000 people in the U.S. Acer plans to file a New Drug Application (NDA) to seek approval for use of Edsivo for treatment of vEDS.

Learn more about ongoing clinical trials for vEDS. 

» For up-to-date information about Edsivo™ (celiprolol) for vEDS, subscribe to receive email updates here.

 

1. Pepin M, Schwarze U, Superti-Furga A, Byers PH. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med. 2000;342:673-680.
2. Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology. Am J Med Genet. 1998;77(31):31-37.
3. Milne RJ, Buckley MT. Celiprolol An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in cardiovascular disease. Drugs. 1991;41(6):941-969.
4. Beridze N, Frishman WH. Vascular Ehlers-Danlos syndrome: pathophysiology, diagnosis, and prevention and treatment of its complications. Cardiol Rev. 2012;Jan-Feb(1):4-7.
5. Ong KT, Perdu J, De Backer J, et al. Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial. Lancet. 2010;376(9751):1476-1484.

Patient Resources

vEDS Ask-the-Expert

Do you have questions you want to ask physicians who are vEDS experts?

Would you like a forum to share the journey you are on and the information that impacts people with vEDS?

We want to hear from you!

Acer Therapeutics is pleased to announce the vEDS Ask-the-Expert program, which will leverage patient/family experts and vEDS physician experts to:

• Provide people with vEDS access to expert doctors who can answer any question you may have about vEDS
• Leverage the expertise only people with vEDS have about vEDS – now is your chance to share with others about vEDS from the your perspective!
• Create a dialogue to ensure people with vEDS and their families have access to the wealth of information you have accumulated

Become a part of the vEDS Ask-the-Expert panel!

Send us your questions, comments, suggestions, and insights about vEDS at ATE@Acertx.com or find us on Facebook or Twitter.

The Ehlers-Danlos Society

The Ehlers-Danlos Society is a nonprofit organization serving the global community to affect change and progress in the world of Ehlers-Danlos syndrome (EDS). Their mission is for all people with Ehlers-Danlos Syndrome to have their right for an early diagnosis, good management, respect, and recognition for their condition. The society is involved with:

• Collaborative research
• Organizing medical symposia and conferences
• Bringing together and uniting the EDS community
• Producing reliable, up-to-date medical literature
• Building and uniting EDS support groups and charities from around the world
• Giving HOPE to all those whose lives are effected by Ehlers-Danlos syndrome

» Find out more at their website.

The National Organization for Rare Disorders (NORD)

The National Organization for Rare Disorders (NORD), a 501(c)(3) organization, is a patient advocacy organization dedicated to individuals with rare diseases and the organizations that serve them. NORD, along with its more than 250 patient organization members, is committed to the identification, treatment, and cure of rare disorders through programs of education, advocacy, research, and patient services.

NORD serves the rare disease community, including patients and their families, patient organizations, researchers, medical professionals, and companies developing orphan products. They also work closely with many government agencies, most notably the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). NORD programs are focused on improving the lives of individuals and families affected by rare diseases.

» Find out more at their website.

The American College of Medical Genetics Clinic Services Search Engine

The American College of Medical Genetics (ACMG) maintains a list of genetics clinics with a comprehensive search engine for people in need of a genetics clinic. You can search based on location, specialty, and your own individual needs.

» Find the search engine at the ACMG website.

Physician Resources

1. Pepin M, Schwarze U, Superti-Furga A, Byers PH. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med. 2000;342:673-680.
2. Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology. Am J Med Genet. 1998;77(31):31-37.
3. Milne RJ, Buckley MT. Celiprolol An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in cardiovascular disease. Drugs. 1991;41(6):941-969.
4. Beridze N, Frishman WH. Vascular Ehlers-Danlos syndrome: pathophysiology, diagnosis, and prevention and treatment of its complications. Cardiol Rev. 2012;Jan-Feb(1):4-7.
5. Ong KT, Perdu J, De Backer J, et al. Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial. Lancet. 2010;376(9751):1476-1484.