Research Update on Loeys-Dietz Syndrome and Marfan syndrome

Dr. Hal Dietz, Victor A. McKusick Professor of Institute of Genetic Medicine and Professor of Pediatrics and Investigator of Howard Hughes Medical Institute at The Johns Hopkins Hospital and Chair of the Loeys-Dietz Syndrome Foundation Medical Advisory Council (MAC), presents “Research Update on Loeys-Dietz Syndrome” at the 2012 LDSF Conference in Baltimore, Maryland, USA. Dr. Dietz discusses the latest on LDS mice model research findings.

Common blood pressure drug reduces aortic enlargement in Marfan syndrome

marfansyndromeuk1.jpgA common drug that is used to treat high blood pressure in the general population has been found to significantly reduce a dangerous and frequently fatal cardiac problem in patients with Marfan syndrome.

Results of the COMPARE (COzaar in Marfan PAtients Reduces aortic Enlargement) study reveal that patients treated with losartan (Cozaar) had a significantly reduced rate of aortic enlargement after 3 years compared to patients who did not receive the treatment.

“Our study is the first large, prospective randomized study to assess the effects of losartan on aortic enlargement in adults with Marfan syndrome, and confirms previous findings in a mouse model,” said lead investigator Maarten Groenink MD, PhD from the Departments of Cardiology and Radiology at Academic Medical Centre in Amsterdam, The Netherlands.

“We’re very excited to see that such a commonly used drug that is not expensive and has a familiar side-effect profile could have a significant effect on this very serious and frightening risk factor for these patients. These findings may change standard clinical management.”

Marfan syndrome, a heritable connective tissue disorder, affects 2-3 in 10,000 people. It causes progressive enlargement of the aorta, making it prone to rupture, which can be fatal in more than 50% of cases. Currently, the only effective treatment is prophylactic surgical aortic root replacement.

Read More: Yottafire

Dysfunctional TGF-beta signaling contributes to Loeys-Dietz syndrome associated aortic aneurysm

marfan syndrome uk logo squarePatients with the connective tissue disorder Loeys-Dietz syndrome (LDS) are at high risk for aortic aneurysm. LDS results in the presence of missense mutations within either of the genes encoding receptors for TGF-β. LDS-associated mutations are predicted to reduce TGF-β signaling; however, aortic tissue samples from LDS patients indicate that TGF-β signaling may be enhanced.

In this issue of the Journal of Clinical Investigation, Harry Dietz and colleagues at Johns Hopkins School of Medicine developed a mouse model of LDS, in which transgenic animals expressing Tgfbr1 or Tgfbr2 with LDS-associated mutations recapitulated human phenotypes. Using this model, the authors determined that even though the mutated TGF-β receptors were functionally defective, there was evidence of increased TGF-β signaling as indicated by elevated Smad2 phosphorylation. Furthermore, development of aortic aneurysms in these mice was ameliorated by treatment with an Angiotensin II type 1 (AT1) receptor antagonist.

In a companion commentary, Alan Daughtery and colleagues at the University of Kentucky discuss the therapeutic implications of this study on the use of AT1 receptor agonists to treat LDS-associated aneurism.

Source: Journal of Clinical Investigation

Learning to Defuse the Aorta

losartanWhen Dr. Hal Dietz arrived at Johns Hopkins University in the 1980s, he became obsessed with helping children with Marfan syndrome, a rare and often fatal disorder that can cause the aorta, the large blood vessel that carries blood from the heart, to grow and grow until it bursts.

“Nothing we were doing seemed to make a difference in their lives,” he said.

These doomed children had a distinctive look that clearly had a genetic basis. They were typically very tall and thin, with long arms, legs and fingers. They often had unusually flexible joints, flat feet and teeth that were crowded in their mouth.

“I decided to study genetics with the sole incentive to identify the gene for Marfan syndrome and ultimately to understand the mechanism,” said Dr. Dietz, now director of the William S. Smilow Center for Marfan Syndrome Research at Johns Hopkins.

That journey has led to surprising discoveries about Marfan’s causes and a soon-to-be published clinical trial of a drug that may help its sufferers.

Dr. Dietz’s work also inspired research that may lead to a blood test that detects enlarged aortas, potentially saving thousands of lives, even among those who do not have Marfan syndrome.

Read More: The New York Times

Tal Golesworthy: How I repaired my own heart

http://www.ted.com Tal Golesworthy is a boiler engineer — he knows piping and plumbing. When he needed surgery to repair a life-threatening problem with his aorta, he mixed his engineering skills with his doctors’ medical knowledge to design a better repair job.

TEDTalks is a daily video podcast of the best talks and performances from the TED Conference, where the world’s leading thinkers and doers give the talk of their lives in 18 minutes. Featured speakers have included Al Gore on climate change, Philippe Starck on design, Jill Bolte Taylor on observing her own stroke, Nicholas Negroponte on One Laptop per Child, Jane Goodall on chimpanzees, Bill Gates on malaria and mosquitoes, Pattie Maes on the “Sixth Sense” wearable tech, and “Lost” producer JJ Abrams on the allure of mystery. TED stands for Technology, Entertainment, Design, and TEDTalks cover these topics as well as science, business, development and the arts. Closed captions and translated subtitles in a variety of languages are now available on TED.com, at http://www.ted.com/translate

If you have questions or comments about this or other TED videos, please go to http://support.ted.com

Common blood pressure drug reduces aortic enlargement in Marfan syndrome – Update

There were no differences in the rate of aortic dissections (0 in the losartan group and 2 controls) or elective aortic surgery (10 in the losartan group and 9 in controls) and no cardiovascular deaths occurred.

marfan syndrome uk logo squareBy European Society of Cardiology, [RxPG] AMSTERDAM, The Netherlands – A common drug that is used to treat high blood pressure in the general population has been found to significantly reduce a dangerous and frequently fatal cardiac problem in patients with Marfan syndrome.

Results of the COMPARE (COzaar in Marfan PAtients Reduces aortic Enlargement) study reveal that patients treated with losartan (Cozaar) had a significantly reduced rate of aortic enlargement after 3 years compared to patients who did not receive the treatment.

Our study is the first large, prospective randomized study to assess the effects of losartan on aortic enlargement in adults with Marfan syndrome, and confirms previous findings in a mouse model, said lead investigator Maarten Groenink MD, PhD from the Departments of Cardiology and Radiology at Academic Medical Centre in Amsterdam, The Netherlands.

We’re very excited to see that such a commonly used drug that is not expensive and has a familiar side-effect profile could have a significant effect on this very serious and frightening risk factor for these patients. These findings may change standard clinical management.

Marfan syndrome, a heritable connective tissue disorder, affects 2-3 in 10,000 people. It causes progressive enlargement of the aorta, making it prone to rupture, which can be fatal in more than 50% of cases. Currently, the only effective treatment is prophylactic surgical aortic root replacement.

In addition to lowering blood pressure, the main benefit of losartan is believed to be its interference with the biochemical process that causes aortic enlargement.

To assess this, the COMPARE study included 233 participants (47% female) with Marfan syndrome from all four academic Marfan screening centers in the Netherlands.

Subjects were a mean age of 41 years, 27% had previously undergone prophylactic aortic root replacement, and the majority (73%) were being treated with beta blockers.

A total of 117 subjects were randomized to receive no further treatment, while 116 were randomized to receive losartan 50 mg daily, doubling after 14 days if there were no side effects.

Aortic enlargement was monitored with magnetic resonance imaging (MRI) for three years of follow-up.

During the study period, if patients in either arm required prophylactic aortic root replacement the decision was left to the discretion of the attending cardiologists based on existing guidelines and anticoagulation therapy was initiated when appropriate.

The study showed that after 3 years aortic root enlargement was significantly less in the losartan group than in controls (0.77 mm vs. 1.35 mm, p=0.014), and 50% of losartan patients showed no growth of the aortic root compared to 31% of controls (p=0.022).

Read More: rxpg news

How I live with Hypermobility Syndrome

yogaHypermobility Syndrome (HMS or Ehlers Danlos Syndrome- Hypermobility Type) is a condition that affects 10-20% of the population. Some people who fit the diagnostic criteria for HMS will have no apparent negative effects as a result, for others it is a debilitating condition that can seriously impair their mobility and manifest with symptoms as diverse as joint dislocations, fatigue and heart murmurs.

I am somewhere in the middle of this scale. I have chronic joint pain, and frequent joint subluxations (partial dislocations). Without appropriate care, joints become unstable, I fall frequently causing damage to my joint surfaces and ligaments. Having lived with this condition for 20 years, I have found ways to manage it, and am able to maintain good mobility within my own boundaries – a far better outcome than my original prognosis. Here are some of the tips that have helped me manage my Hypermobility Syndrome:

Use it or lose it – keep active.

I know I am not going to be running any marathons, but that does not mean I have to submit to the sofa completely. I choose ways to keep active that within my capabilities.

Can you swim? Maybe breaststroke is too much for your hips, so how about crawl? How about some gentle yoga? Learning to maintain your alignment whilst gently building strength in your posture is really beneficial. Be aware that I am not advocating stretching for flexibility here, but strong yoga postures to stabilise the joints. Can’t stand? How about chair yoga ?

Even if all you can do today is sit up in bed for a bit, challenging your body in a sympathetic manner will not only help you maintain your physical ability, but will also make you feel good.

Make your plans as flexible as you are.

Some days I wake up feeling spritely and good, some days I wake up creaky, aching and tired. Sometimes I get better as the day progresses, sometimes worse. I have to be prepared to adjust my plans accordingly because I have learned that there is no point putting more strain on myself unnecessarily

Hormonal changes and pregnancy can seriously impact the state of your ligaments, so always be mindful, and non-judgmental, of your capabilities at this moment.

Read More: Yahoo Lifestyle