Connective Issues Winter 2023

Research Provides Hope for Our Families

Winter 2023

NEW ACC/AHA AORTIC DISEASE GUIDELINES

HOW TO ADVOCATE FOR CHANGE

STUDIES & GRANTS SHOW PROMISE FOR THE FUTURE

The Marfan Foundation is a nonprofit organization that saves and improves lives while creating community for all individuals with genetic aortic and vascular conditions, including Marfan, Loeys-Dietz, and Vascular Ehlers-Danlos syndromes. We work tirelessly to advance research, serve as a resource for families and healthcare providers, and raise public awareness. We will not rest until we have achieved victory.

Since our inception, the Foundation has focused on advancing science to extend the lives and enhance the lives of the people we serve. We are incredibly proud that, in our 40 years, we have played a critical role in bringing together the scientific community and supporting research in ways that make a di ff erence for those living with Marfan, Loeys-Dietz, and VEDS.

Through our expanded Research Grant Program, we recently awarded $620,000 in new grants to physicians and scientists, including the largest grant awarded in our history – the Everest Award – bringing our total current funding to $1,285,500. In addition, through our Loeys Dietz division, we funded a potentially ground-breaking study that is an exciting opportunity for the future treatment of Loeys-Dietz syndrome. In August, we convened our largest international science meeting ever, Science in Paris, which featured dedicated day-long programs on VEDS and genetic aortic conditions, as well as two days on Marfan and Loeys-Dietz. We brought together more than 270 of the world’s leading researchers and clinicians, along with dozens of young investigators embarking on their careers with incredible passion for unraveling the mysteries of connective tissue conditions, as well as genetic aortic and vascular conditions. And while in Paris, we also learned of the publication of new data emanating from a meta-analysis surrounding the losartan-beta blocker clinical trial on Marfan that we were involved in since its inception. That investment continues to reap benefits. You can read about all of this exciting research news in this edition of Connective Issues . We are hopeful these studies and collaborations will lead to advances in life-saving care, treatment, and ultimately, a cure for those living with Marfan syndrome, Loeys-Dietz, VEDS, and related genetic aortic and vascular conditions. As we enter 2023 and reflect on what we’ve helped to bring about in research over the past year, I can truly say that the future has never looked so promising for our community. Many thanks to Dr. Josephine Grima, our chief science o ffi cer, and an extraordinary research community for leading the way in our success. Finally, we want to thank Cory Eaves, as he will soon conclude a remarkably successful tenure as board chair during one of the most challenging times in our history. And, we are thrilled to welcome Bert Medina as our chair-elect and look forward to his leadership. With your continued support, we can’t wait to see the progress we can all make together in the New Year! Thank you for your ongoing support of research and progress. Best wishes for a happy and healthy 2023.

Learn more and get involved at Marfan.org.

CONNECTIVE ISSUES Winter 2023 VOLUME 42 | NUMBER 1 Connective Issues is the newsletter of The Marfan Foundation. It is published three times per year.

Inquiries should be addressed to: Publicity@Marfan.org

This issue of Connective Issues is made possible through a grant from the Chu and Chan Foundation.

Michael L. Weamer President & CEO

THE MARFAN FOUNDATION 22 MANHASSET AVENUE PORT WASHINGTON, NY 11050 516-883-8712 | 800-8-MARFAN MARFAN.ORG

ON THE COVER: New advances in research are providing hope for our community, including the Hervatin family from Arizona. Lincoln, held by his mother, has Loeys-Dietz. Read his story on page 13.

Study Provides Compelling Results for MARFAN TREATMENT

In late August, The Lancet published the findings from a meta-analysis of seven global clinical trials with data from 1442 participants with Marfan syndrome. Funding from The Marfan Foundation assisted researchers from the United Kingdom, Canada, Spain, United States, Netherlands, and Belgium in the analysis. The primary aim of the study was to estimate the e ff ects of angiotensin receptor blockers

Hospital, the lead author of the study. “We think that is really important for patients because it will slow the rate at which the aorta expands and that may delay the need for surgery.” The study also provided indirect evidence supporting the use of beta blockers in Marfan syndrome, adding to the evidence already available for this treatment.

Supporting research is one of The Marfan Foundation’s critical mission areas. Providing funding to Dr. Pitcher and his colleagues at Oxford University to take on this challenging task of analyzing all eligible trials for which data was available will provide significant clarity for therapeutic options for our patient community and help to improve the lives of those with genetic aortic and vascular conditions. This meta-analysis included the clinical trial by the National Heart, Lung, and Blood Institute and the

(ARB) and beta blockers on the rate of aortic root enlargement in patients with Marfan syndrome. The results indicated that ARBs (such as losartan and irbesartan) significantly reduce the rate of aortic enlargement by about half with or without beta blockers. This e ff ect was generalizable to di ff erent types of patients. In particular, ARBs were e ff ective even among those already taking a beta

blocker. The rate-reducing e ff ect was particularly large among patients with a disease-causing (pathogenic) FBN1 gene mutation compared to those without an FBN1 variant, providing biological support for the e ff ect. “The meta-analysis has shown that the two treatments under study, angiotensin receptor blockers and beta blockers, are e ff ective in patients with Marfan syndrome,” said Alex Pitcher, DPhil, Oxford University

p Alex Pitcher, DPhil, with Shaine Morris, MD, at Science in Paris

Pediatric Heart Network—and supported by The Marfan Foundation—which showed losartan was e ff ective in the treatment of Marfan syndrome. This initial trial continues to spur important findings for our community.

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ACC/AHA Announce New Aortic Disease Management Guidelines

New guidelines for the diagnosis and management of aortic disease were published in the fall in the Journal of the American College of Cardiology and the journal, Circulation . These guidelines, which were created by a team of medical experts on behalf of the American College of Cardiology and American Heart Association, provide recommendations on the diagnosis, evaluation, medical therapy, endovascular and surgical intervention, and long-term surveillance of people with aortic disease based on evidence available in the literature and, in some instances, based on expert consensus opinions. They include specific recommendations for those with syndromic and non-syndromic genetic aortic conditions as well as other types of acute aortic syndromes. They also emphasize the role of shared decision-making. The guidelines provide support for: • Seeking surgical treatment from high-volume centers with experienced surgeons as part of a multi disciplinary team for asymptomatic patients with extensive aortic disease, those who might benefit from complex open and endovascular repairs, and those with multiple co-morbidities. • Genetic testing for people with syndromic features, family history of thoracic aortic disease, or early onset of disease (under the age of 60). • Thoracic aortic imaging of family members of a ff ected individuals to screen for asymptomatic thoracic aortic disease in specific cases. Tips from patient advocate, Maya Zimmerman-Brown, MPH ✓ Come prepared to your appointment with relevant questions. ✓ Bring a copy of the guidelines to your physician. ✓ Listen to your doctor’s rationale and have a discussion. ✓ Look for a second opinion.

If you are going to address an aorta at a smaller size, you really need to have a lot of experience, both in doing the procedure and also in understanding the disease process and risks to the patient undergoing that procedure. ~Dr. Abe DeAnda

• Open surgery is recommended over thoracic endovascular aortic repair in patients with Marfan, Loeys-Dietz, and VEDS who have a descending thoracic aortic aneurysm that meets criteria for intervention and have suitable anatomy. The new guidelines were developed in collaboration with and endorsed by the American Association for Thoracic Surgery, American College of Radiology, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, and Society for Vascular Surgery. To watch a recording of our webinar with more information about the new guidelines and how they a ff ect people with Marfan, Loeys-Dietz, VEDS, and other genetic aortic and vascular conditions, visit our YouTube Channel. The presenters were members of the ACC/AHA writing committee for the guidelines: Dr. Alan Braverman, cardiologist, Washington University School of Medicine in St. Louis; Dr. Abe DeAnda, cardiothoracic

surgeon, University of Texas Medical Branch (UTMB) in Galveston; and Maya Brown-Zimmerman, MPH, patient advocate. To view specific recommendations for Marfan syndrome, Loeys-Dietz, and pregnancy, scan the QR code.

A multidisciplinary team is critical in shared decision-making as the vast majority of cardiac surgeons perform less than or equal to two aortic root surgeries in a year. It’s not a common surgery for the vast majority of cardiac surgeons. Having complex aortic surgery, especially when very low risk is necessary, it is important to see a surgeon with experience. ~Dr. Alan Braverman

To get assistance finding a surgeon or a coordinated clinic, visit Marfan.org and click on Find a Doctor on the home page to download our institution directory. Or you can connect with our Help & Resource Center at Marfan.org/ask.

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Foundation Announces Largest Research GRANT Total research currently funded by the Foundation is $1.285 million The Marfan Foundation has awarded $620,000 in new grants to physicians/scientists as part of its Research Grant program bringing the total current funding to $1,285,500. The new grants include a one-year Everest award and four, two-year grants including one Career Development Award, and three Innovators Awards. “Research funding from the Foundation has provided critical seed money to established scientists and has successfully enhanced the pipeline of researchers who are interested in genetic aortic and vascular conditions,” said Craig T Basson, MD, PhD, chair of the Foundation’s Scientific Advisory Board. “We are now at a crucial juncture where we can more strategically focus on transformational science and aim for cures for these conditions. The Everest Award was designed to promote longer, multi-disciplinary, collaborative grants that will help us reach these goals.” This is the largest grant mechanism initiated by the Foundation. It can provide up to four years of funding for a total of $880,000 if yearly milestone goals are met based on evaluation by the Scientific Advisory Board. First Everest Award Recipient The Foundation presented the first Everest Award to Joseph W. Turek, MD, PhD, MBA, an academic pediatric cardiac surgeon at Duke University. Since 2017, Dr. Turek has served as chief of pediatric cardiac surgery and Other New Grant Recipients ★ CAREER DEVELOPMENT AWARD - $100,000 Marie Billaud, PhD, Brigham and Women’s Hospital Mitochondria – ECM crosstalk in aortic SMCs of Marfan Patients ★ INNOVATORS AWARD - $100,000 Enid Neptune, MD, Johns Hopkins University Defining Alveolar Epithelial Phenotype in Marfan Lung Disease ★ INNOVATORS AWARD - $100,000 Delphine Gomez, PhD, University of Pittsburgh Alteration of H34Kme2 in Marfan syndrome: A driver of aortic dilation ★ INNOVATORS AWARD - $100,000 Bart Loeys, MD, PhD, University of Antwerp Exploration of a novel biomarker for thoracic aortic aneurysm and dissections (See page 12 for details) To view all past grant recipients, visit Marfan.org/research/funded-grants.

p Joseph W. Turek, MD, PhD, MBA

executive co-director of Duke Children’s Pediatric & Congenital Heart Center. The Foundation awarded his project, TRPC4/ATR1 Dual Antagonism Blocks Marfan Aortopathy, $220,000 for one year. Current medical therapies slow the rate of aortic growth in people with Marfan syndrome, but they do not eliminate the need for surgery. In preliminary work, Dr. Turek and his team demonstrated that a novel pathway is involved in aneurysm formation in people with Marfan. In animal studies, when a critical protein in this pathway is blocked with medication, these aneurysms do not form. Moreover, this critical protein is found in abundance in the aorta of people with Marfan who require surgery, underscoring its relevance to aneurysm formation. The Marfan Foundation Everest Award will allow Dr. Turek and his team to more specifically characterize this pathway, discover drugs that can e ff ectively block the critical protein preventing aneurysms, and identify biomarkers found in the blood that can evaluate the e ff ectiveness of the drug. Ultimately, Dr. Turek hopes this results in better medical treatment for this devastating

complication of Marfan and that people with Marfan can one day avoid surgery altogether. To support research and progress on Marfan, LDS, and VEDS, please scan the QR code or visit Marfan.org/ donate.

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Winter 2023

SCIENCE IN PARIS Brings Toget and Clinicians from All Over the W

The Marfan Foundation and its divisions hosted Science in Paris in August 2022, bringing together more than 270 registrants from 21 countries, which made it our most well-attended scientific conference in our history. Attendees included students, postdocs, and a number of leaders from international volunteer organizations as well as the leading experts in the field. The four-day event featured three separate but connected meetings focusing on the latest research on genetic aortic and vascular conditions, including the 11 th International Symposium on Marfan, Loeys-Dietz, and Related Conditions (two days); the DEFY Foundation 5 th Scientific Meeting on Vascular Ehlers-Danlos Syndrome (one day); and the 7 th GenTAC Aortic Summit (one day). The program included: • 62 oral presentations at the International Symposium on Marfan, Loeys-Dietz, and Related Conditions • 20 oral presentations at the DEFY VEDS meeting • 20 oral presentations at the GenTAC meeting • 165 poster displays of research studies over four days “It is so encouraging to see the many young researchers learning from the leaders in the field, who are mentoring them while continuing to search for answers,” said Josephine Grima, PhD, chief science o ffi cer for the Foundation. “These experiences and collaborations are essential to the future of research for these conditions.”

p Talha Niaz, MBBS, Laura Muiño Mosquera, MD, PhD, Anna Huguenard, MD, and Marc Schönholzer, MSc

New exciting research studies were presented at the meetings. Here are a few highlights. Marfan Syndrome Studies • Data analysis from multiple trials confirm that losartan or irbesartan reduces the rate of aortic enlargement with or without beta blockers. See related article on page 3. • Studies suggest mild to moderate exercise is safe and possibly protective. (Watch the related video on our YouTube channel.) • Multiple new signaling processes emerge as viable therapeutic strategies in mice. Loeys-Dietz Syndrome Studies in Mice • Studies are looking to identify and validate biomarkers of aortic health. (See related article on page 12.) • Processes that cause altered response to mechanical stresses in the aortic root are being investigated. • Methods to restore microfibril sheath in LDS3 may help reduce degeneration in the aorta.

This is the only meeting devoted to the connective tissue disorders associated with aortopathies thus it is vitally important to those of us caring for these patients. The meeting brings perspective from physicians in many disciplines from

around the world keeping us updated on the current research and also very instrumental to my practice.

Science in Paris is truly what a medical conference is supposed to be – a warm, collaborative gathering of brilliant minds to discuss research, engage in meaningful conversation, and create long-lasting professional partnerships and even closer friendships.

Tala Curry

Robert Peña, MD, with Sherene Shalhub, MD

Rodrigo Barbosa De Souza, PhD

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Congratulations to the Science n Paris Scholarship Winners

ther Researchers World Vascular Ehlers-Danlos Syndrome Studies in Mice • Genes responsible for VEDS familial variability were identified. • Cells that line the blood vessels contribute to cell signaling leading to vascular rupture. • Decreasing levels of androgens and mineralocorticoids help reduce arterial rupture. • Certain statins reduced aortic wall stress which may indicate added value in the drug therapy. Bicuspid Aortic Valve (BAV) • Aortic tortuosity related more to tubular dilation compared to root dilation. • Pregnancy in BAV related aortopathy in a study of 47 patients with 103 pregnancies seems safe in women with aortic root z scores over 40 mm and there were no dissections during pregnancy or post-partum. • When genetic testing for other genetic aortic conditions is done in patients with BAV phenotypic features or family history of aneurysm or sudden death, there was a 16% positive rate. The GenTAC Aortic Summit tackled several controversial issues to help clarify a variety of clinical management opinions as well as guidelines for di ff erent countries. These are the very di ffi cult clinical decisions facing surgeons every day. • Should the size of the aneurysm for surgical intervention for BAV be the same or di ff erent as non genetic aortopathies? • What are the pros and cons of operating on ascending intramural hematoma? • What are the pros and cons of stenting a type B dissection? This meeting has it all – great science, great clinical information, and most importantly, a tangible connection to patients. This meeting exceeded my expectations in every respect.

DEFY VEDS Scientific Meeting (Provided by the DEFY Foundation) • Caitlin Bowen , Johns Hopkins University – A Gene Variant and Mechanism for a Potent Protective Modifier of Vascular Ehlers Danlos Syndrome International Symposium on Marfan: NIH Supported • Lauriane Sedes , Icahn School of Medicine at Mount Sinai – Loss of TGF β Signaling in the Outer Perichondrium Causes Longitudinal Bone Overgrowth in Marfan Syndrome • Anna Cantalupo , Icahn School of Medicine at Mount Sinai – Combination Therapy Targeting the Major Angiotensin II Receptors Prevents Thoracic Aortic Aneurysm Formation in Marfan Syndrome Mice by Reversing eNOS Uncoupling • Marc Schönholzer , Swiss Foundation for People with Rare Diseases – Insights into the Biomechanical Integrity of the Aorta in Mice Modelling Hereditary Aortic Diseases • Anna Huguenard , Washington University in St. Louis – Intracranial Aneurysms in Patients with Loeys-Dietz Syndrome • Palca Shibale , University of Washington – Presentation and Management of Arteriopathy in Marfan Syndrome. • Tala Curry , University of Arizona College of Medicine-Phoenix – Marfan Syndrome Accelerates Cerebrovascular Aging and Blood-Brain Barrier Permeability • Rodrigo Barbosa De Souza , University of São Paulo – Compensatory Mechanisms in the Tunica Media of Aortic and Mesenteric Arteries of the mg lpn Dominant-negative Mouse Model of Marfan Syndrome. GenTAC Aortic Summit: NIH Supported • Talha Niaz , Texas Children’s Hospital – Role and Yield of Clinical Genetic Testing Among Patients with Bicuspid Aortic Valve and Aortic Dilation Referred to the Cardiovascular Genetics Clinic • Laura Muiño Mosquera , Ghent University Hospital – Clinical and Genetic Correlates of Mitral Valve Pathology in Patients with Heritable Thoracic Aortic Disease: Results from the Montalcino Aortic Consortium • Robert Peña , George Washington University Hospital – Revisiting the Combination Aortic Dissection Detection Risk Score (ADD-RS) and D-Dimer Algorithm for Acute Aortic Syndrome (AAS) Rule-Out in the Emergency Department

This is one of my favorite scientific meetings as it unites people from all different disciplines and levels of training about genetic disorders with predisposition for aortic dissection. I always learn a lot and leave energized with new ideas for research and collaboration.

Caitlin Bowen, MD, PhD, with Anthony Yasick, MD

Anna Cantalupo, PhD, and Palca Shibale, BS

Talha Niaz, MBBS

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Recovery After Surgery Provides NEW PERSPECTIVE

A self-proclaimed “horse girl,” Molly was used to hard work in the barn, throwing 80-pound bales of hay. As a longtime, active equestrian, she was strong and fit. But a few weeks before she was set to start her freshman year at college in 2017, she was short of breath, dizzy, and didn’t feel right. Due to a family history of aortic dissection, Molly had routine testing most of her life. Her scheduled MRI revealed the dimensions of her aorta had grown since her last appointment, and her cardiologist at Cleveland Clinic, Dr. Ken Zahka, recommended surgery. One month after the MRI, Molly went in to have her aorta repaired by Dr. Eric Roselli, Chief of Adult Cardiac Surgery and Director of the Aorta Center at Cleveland Clinic. “While my doctor was performing the surgery, my aorta just dissected,” she said. “What was expected to be a five-hour surgery turned into 10 hours. I was really lucky that I did dissect in the OR, and Dr. Roselli was careful to check everything and make the needed repairs. When I came out of surgery, I was told that I was a walking miracle.” Molly’s recovery from surgery was di ffi cult, both mentally and physically. “It was supposed to be my first semester of college,” she said. “To make the choice to stay home and have heart surgery while watching everyone else go to college was challenging, but I knew it was something I needed to do.” She worked hard to recover, going to cardiac rehab and achieving milestones - walking upstairs, going to the mailbox, and walking around the lake in her neighborhood. After three months of recovery, Molly started to slowly resume her routine. She went to college and, several months later, she was back in the saddle. “I thought I could just jump back into my activities,” Molly said. “I didn’t realize how much strength I had lost. I had to cut out a few things, but I tried to find a way to do the things I love safely, and although recovery was challenging, it gave me a new perspective on life for which I am very grateful.” Self-Awareness Leads to Prompt Care Since her recovery, Molly was living what she considered a normal life - riding horses and going to school. Through genetic testing in 2020, she was o ffi cially diagnosed with a rare connective tissue disorder related to Marfan syndrome and continued with routine monitoring. In January 2021, while she was in the barn, she felt short of breath, dizzy, and fatigued along with pressure in her chest. Molly knew something was wrong and called her mother to come to the barn.

p Molly with Maverick

“I sat down in the barn, and I could feel my aorta dissect,” said Molly. “It was like a knife down the center of my abdomen and the worst pain I have ever felt. I knew exactly what was happening, so I immediately called Dr. Zahka.” Dr. Zahka instructed her to come to the emergency department where sta ff would be waiting for her to get a CT scan upon arrival. Molly received a follow-up text from him when she was en route: Dr. Roselli knows what is going on and will drive the plan. We will get you through this. You have a great team. Imaging revealed that her aorta had once again dissected, but this time with no warning signs. Dr. Roselli performed another successful repair. Molly is expecting to have another surgery to further reinforce her aorta in the future. She continues to go to Cleveland Clinic at least every six months for scans and tests as part of her monitoring. A Trusted Care Team Provides Peace of Mind Molly credits her cardiac team of physicians and nurses with seeing her as a person, not just a patient. She said the relationships established with her care team give her the confidence to push forward with everyday life. “It’s so important to have a team you can trust and that you know will have your back,” she said. “It makes decisions and challenging conversations easier. I trust that if I need anything, Dr. Zahka will call or text me back in a heartbeat.”

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In addition to the skilled physicians, Molly also gives credit to the team of nurses who were instrumental in her care while at the hospital. She said their attention to detail and positivity got her through a di ffi cult and painful two weeks in ICU. Staying Active and Helping Others At 23, Molly lives her life to the fullest, pledging to live in the present and focus on activities that bring her joy. She will graduate in May from Case Western Reserve University with her master’s in developmental psychology and early intervention, and she hopes to have a career in pediatric cardiology. She currently works at an equine-assisted mental health facility helping people overcome obstacles and move toward positive growth. Making her health a top priority, Molly takes the time to monitor her cardiac fitness and send workout summaries detailing her heart rate to Dr. Zahka. And she finds ways to volunteer and spread awareness about connective tissue conditions including raising funds for the Foundation’s Cleveland Walk for Victory. “My health challenges have been a reminder that life doesn’t always go your way, but it is so helpful to make the best of what you have been given,” she said. “I’ve been through a lot, and I want to help people who are going through something similar in any way that I can.” Molly encourages others who may be in a similar situation to focus on what is known – what is directly in front of them and not to get wrapped up in the what-ifs, falling down the rabbit hole of fear and anxiety. “Break it down and take it a step at a time,” she said. “If you think about the whole picture, you can get really overwhelmed and taken away from the present. Be grounded in the present. What I know now is I’m alive, I have a great care team to take care of me, and I will get through this.”

The Marfan Foundation is honored to announce Bert Medina has been named chair-elect of its Board of Directors. He will begin his term in July 2023. Bert has been involved with the Foundation over the years as secretary of the board of directors, executive committee member, chair of the Health Equity Task Force, co-chair of the Spanish Summit, and a volunteer leader in building the Southern Florida region of The Marfan Foundation. Originally from Cuba, Bert lives in Fort Lauderdale, FL, and has worked in the communications industry for nearly 40 years. He currently serves as president and CEO of WPLG (ABC Miami) and was previously vice president and general manager. Bert has also held a variety of executive management positions during a 13-year tenure with Univision. He served as senior vice president and operating manager of the TeleFuturaTelevision Network, a unit of Univision Communications, where he propelled it to the number two Spanish language broadcast network. “I could not be more excited that Bert will follow in my footsteps as chair-elect of the Foundation’s Board of Directors,” said Cory Eaves, current board chair. “Bert has every quality that we could hope for in a chair. In addition, he has great enthusiasm and is totally committed to the Foundation’s success and moving our collective vision forward. I look forward to continuing to partner with Bert, our volunteers, and the members of our sta ff in serving our international community of people with genetic aortic and vascular conditions.” To learn more about the Foundation board, visit Marfan.org/about/team. The Foundation Announces Board Chair-Elect

p Molly and her cardiologist, Ken Zahka, MD

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Winter 2023

Your Voice Can Impact Change

After spending 18 years in Washington, including many on Capitol Hill, Tyler Roberts volunteers his time to help those in the connective tissue condition community better engage with members of Congress to get their voices heard to enact change. A former House and Senate healthcare sta ff er, lobbyist, and now public a ff airs professional, Tyler knows the ins and outs of Washington and provided insight on how to best advocate to elected o ffi cials. Tyler, who has Stickler syndrome, first connected to The Marfan Foundation at the Senate bu ff et line right before the pandemic.

with your elected o ffi cials to advocate on behalf of our community. “It’s important to make sure your faces are seen and voices are heard to enact change in DC,” said Tyler. Tyler provided his top three tips when communicating with an elected o ffi cial: 1. Don’t Be Afraid: Many people are nervous or apprehensive at first, but there is no reason to be. Tell your truth and understand it is a conversation. 2. Tell Your Story: Members of Congress

always love anecdotes and hearing from their constituents. Be sure to cite specifics and speak from the heart; don’t talk too broadly – make it personal. 3. Be Persistent: Don’t think “one and done.” It takes time to make change and establish trust so start a dialog, build a relationship, stay engaged, and follow up. That is what members of Congress are here for – to hear from constituents. “I think many people see DC as this weird bubble and not part of their life,” Tyler said. “Congress is for the people. It was created so

“By happenstance, I saw a group from The Marfan Foundation there for Congressional Lobby Day, and I struck up a conversation,” said Tyler. “After that, I became involved with the Foundation to help with strategy and fundraising.” Since the first meeting, Tyler

has participated in two Walk for Victory fundraising events in DC. He was also a guest speaker at the Foundation’s International E 3 Virtual Summit in 2020 where he shared his story about Stickler syndrome and his experiences with four detached retinas and countless eye surgeries. “Sticker has impacted my life, and I want to remain engaged with the Foundation to help inform the community,” stated Tyler. “It is important to visit members of Congress and tell your story to advocate for the Foundation to better increase research and funding. Treatment options and outcomes can be impacted through Congress.” As Congress reopens more to the masses since COVID, Tyler encourages those who want to become engaged to make appointments at local o ffi ces with members of Congress or their sta ff . You can also start a letter-writing campaign to start developing a relationship with them. If you will be in Washington DC, you can arrange to meet

“DC is a great place to engage and advocate, so don’t be afraid to jump in. Voice can impact change.” here, but what most people don’t realize is there is so much good that comes out of DC, and there is so much bipartisanship that is not covered in the media. Advancing funding for rare conditions is always bipartisan and important .” The Foundation will keep you up-to-date throughout the year on any legislation a ff ecting our community. If you need more advice on engaging DC o ffi cials, please reach out to Tyler Roberts directly at atyroberts@gmail.com. we can come out and petition our legislators to help guide them on the issues. DC is scary and there is so much ugly politics out

We encourage community members to reach out to their elected o ffi cials to proclaim February as Marfan Awareness Month in each state. Scan the QR code now to get started!

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The Marfan Foundation and the GenTAC Alliance Push Research Collaborations Forward 

The GenTAC Alliance, a division of The Marfan Foundation, continues to put team science first and serve as a global educator for the community of physicians, scientists, and healthcare professionals focused on advancing care for all forms of genetic aortic and vascular conditions. The GenTAC Alliance accomplished much in the past year: • The Aortic Summit, part of the Foundation’s international research symposium, Science in Paris, focused on discussions of management controversies and di ff erences between country guidelines for these conditions and how these issues need to be addressed with outcome data. • Several GenTAC investigators received a multi center, multi-year, multi-million dollar grant from the LeDucq Foundation to investigate triggers for aortic dissection. The study begins in January 2023.

p Attendees attend the poster session at the 7 th GenTAC Aortic Summit, part of the Science in Paris meeting in late August

• GenTAC investigators compiled a compendium of registries for researchers to easily view the number of participants as well as certain clinical aspects so scientists can target registries with resources to answer specific study questions. This will appear on the new GenTAC website, which will relaunch in 2023. • Eight publications appeared in the March 2022 journal entitled Seminars in Vascular Surgery. These studies resulted from the Aortic Dissection Collaborative, a research initiative conducted by members of the Alliance. • GenTAC Working Group members held several educational webinars targeted to researchers and physicians. To learn more about GenTAC, please visit GenTACAlliance.org.

p Attendees joined a general session at the 7 th GenTAC Aortic Summit in Paris

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The Loeys-Dietz Syndrome Foundation awarded a multi-year grant to Bart Loeys, MD, PhD, University of Antwerp, for his study, Exploration of a Novel Biomarker for Thoracic Aortic Aneurysm and Dissection . The grant began July 1, 2022, and extends through June 30, 2024. Here is why biomarker research is important to the LDS community and the intention of the study. u What is a biomarker? A biomarker is a measurable substance in blood. Its presence is indicative of a normal or abnormal process, or of a condition or disease. During previous research on the expression profiles of genes in the aneurysmal aortic wall of three di ff erent Marfan and Loeys-Dietz syndrome mouse models, a gene was identified that was highly expressed in all three models. This protein is a novel player in the pathogenesis of thoracic aortic aneurysms and its Novel Biomarker Grant Awarded to Dr. Bart Loeys ? Imaging of the aorta (MRI, MRA, CT scan) is the current method to determine rate of aortic root enlargement and aortic risk. At present, there are no biomarkers that could predict the existence of a thoracic aortic aneurysm or the occurrence of a thoracic aortic dissection. The identification of such a biomarker would be of great help to: • Determine if new therapeutics are helping in the reduction of aortic enlargement. • Find methods to validate e ff ectiveness of new drugs and make clinical trials shorter and less expensive. • Develop an easy, e ffi cient, and e ff ective blood test to monitor aortic health. u What will be done during the study? INVESTIGATE if the serum levels of this protein in Marfan and Loeys-Dietz mouse models correspond to the thoracic aortic aneurysm severity and progression. GATHER EVIDENCE in serum samples of a ff ected people with thoracic aortic aneurysm and dissection to validate if this protein is also in humans and can possibly be used as a biomarker for thoracic aortic aneurysm and dissection. IDENTIFY THE CELLULAR SOURCE of this protein in people with Marfan and Loeys Dietz through a stem cell-derived model and understand the mechanisms that cause this protein to increase for future therapeutic targets. highest expression is in the aortic wall. u Why is biomarker research important?

p Bart Loeys, MD, PhD

u Do we anticipate additional research to be continued after the grant cycle is completed? If the research has a positive result, the study would need a longer project with many additional samples to correlate blood protein levels with thoracic aortic aneurysm progression and severity. If validated, this protein level could be used to test therapeutic compounds with the “simple” measurement of the blood levels, and those therapeutics that diminish the protein level would be beneficial for the treatment of aortic aneurysm. u How will this help people with LDS? Our hope is that this research can prove that the level of this protein in the blood can give an indication of aortic health and possibly be used as a predictor of aortic dissection. This research could also be used to help determine if new therapeutics are helping in the reduction of aortic enlargement, which is greatly

needed for drug companies to make clinical trials less long and less expensive. To learn more, please visit Loeysdietz.org/biomarker. Scan the QR code to download an infographic.

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FOR LINCOLN Hope

By Julie Taubert, Glendale, AZ When our 12-month-old, Lincoln, was diagnosed with Loeys-Dietz syndrome, the first thing we and all of our providers thought was - what is Loeys-Dietz syndrome and how do we treat it? A few said, “It’s like Marfan syndrome, right?” We

heart medication with his cardiologist and, based on published studies, why higher doses are needed in LDS patients. I have been able to put some of my fears at ease after reading about common and uncommon manifestations of LDS type 2. Having research available also meant that I was aware of things to watch out for and what we should be concerned about. described in 2005, ave been made in

Since LDS was first h d h great strides understan how to and f dia k

quickly learned through li from previous conference Foundation’s YouTube ch it was similar, but there ar critical di ff erences. We learned that, in LDS the aorta has a lower threshold for dissections and ruptures, and there c be GI problems, allergies, additional skeletal problems, and more. As a parent, you want to make sure you are doing everything in your power to keep your child as healthy as possible. It was overwhelming to lear about Lincoln’s diagnosis and also learn that we had help educate our son’s pr about his condition and w they should get the most information. I took a copy of the Loe , a

stening to lect e s a e ur s on the nnel that some

ing the condition and elp make lives longer ller for people who are nosed with LDS. We ow what types of exercise re appropriate and what medication will stabilize or slow the progression of aortic growth. And with the latest research into an LDS biomarker (see related article on page 12), we may get to witness a whole new way o monitor and treat those ith Loeys-Dietz syndrome. We are thankful for all people who work hours d trying to find answers many questions that S families daily. The future nd full of hope for the u g t w n n a

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y nity, thanks to all of the wonderful people who dedicate their lives to finding answers about LDS. With all of the amazing research that has been done on LDS, we are able to keep our Lincoln as healthy as possible.

syndrome: A primer for diagnosis and management to our pediatrician, who had not heard of LDS. That resource gave her a basis for aiding in our son’s care. We also discussed the correct dosing of Lincoln’s

To support the life-saving work of the Loeys-Dietz Syndrome Foundation, visit https://bit.ly/SupportLDS.

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Finding Community Meant Not Being Alone

By Tyler Farley, Raleigh, NC One day I was a normal kid, then the next I learned I had VEDS. I was diagnosed in 2014 at the age of 17 just before I was just about to graduate high school. I was very active before my diagnosis – weightlifting and playing sports like travel soccer, basketball, and golf. Looking back, the only signs were that I always bruised easily and I was born with club feet. One day, I randomly felt a pain I’ll never forget, and it led me to go to the ER. After hours of waiting, I got a CT scan that revealed I had a perforated bowel. From there it was a roller coaster. I was admitted for two weeks as the doctors could not figure out why this was happening. I was even asked if I ate nails or glass! Then a resident surgeon noticed my club feet and put the pieces together. I was told I had

VEDS; I had no idea what that was. At 18, I went from one pediatrician to a new team of doctors. I felt like I had no resources, and I was stuck. Nothing prepared me for this diagnosis, but I kept strong and

“It took me eight years to find anyone just like me.”

p Tyler and his dog, Stormy

It took me eight years to find anyone just like me. Now 26, I am so glad to have

others I can talk to about VEDS because I was alone for a long time. The VEDS Movement helped me get the resources and support I needed, and now I’m doing my part to help others. I don’t take things and people for granted, and I’m super grateful for all I have. I don’t know how much time I have to live with this condition, but I know I’m going to do my best to have the time of my life while I can! Tyler, who lives with his dog, Stormy, enjoys hanging out with his friends in Raleigh, NC, going to Carolina Hurricanes hockey games, and living life to the fullest.

focused on what needed to be done to have a great life. I went to college, graduating in 2019 with a bachelor’s degree in finance. I have a great job with good healthcare, and I set myself up to be comfortable with VEDS for now. I am still active in some sports like hiking and skiing. I used those voices that told me I couldn’t do anything to motivate me to keep grinding. My advice is to do what you want to do. You have to be cautious, but there’s no point in sitting around wasting time. Any diagnosis is not easy, especially VEDS, but there has to be some light at the end of the day.

To share your VEDS story, visit the Share Your Story page under the Community Corner tab at TheVEDSMovement.org. Be sure to check out the numerous helpful resources and support groups that we o ff er our community.

Awareness Project Educates Emergency Medicine Professionals on VEDS The VEDS Movement continues to make strides in medical education about Vascular Ehlers-Danlos syndrome (VEDS). Educating healthcare professionals in hospital emergency departments is a high priority because too often people with VEDS have sudden medical complications that can be

deadly if they are not identified and treated quickly. As part of The VEDS Movement’s targeted outreach e ff orts, the American Academy of Emergency Medicine has

approved a VEDS CME course, created by The VEDS Movement and the Sullivan Group for its members. This course will be available free to all AAEM members throughout 2023 thanks to a grant from the Daskal Family Foundation. Scan the QR code to learn more about this project.

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TEAM VICTORY Crosses the Finish L We would like to salute our amazing team of 10 runners who endured the grueling New York City Marathon on November 6 to raise awareness and funds. Our members not only finished the 26.2-mile race but they raised more than $35,000 to support the Foundation’s programs and services for the Marfan syndrome, Loeys-Dietz, and VEDS communities. We applaud each of them for the mental and physical toughness they demonstrated to complete the largest marathon in the world!

ine

★ Ivana Batstra, Amsterdam, Holland ★ Edward Cooning IV, Indianapolis, IN ★ Grace Ehrbar, Columbus, OH ★ Andrea Friedman, Manalapan, NJ ★ Julia Holmes, Amsterdam, Holland ★ Robyn Li, New York, NY ★ Kristine O’Connor, Phoenix, AZ ★ Rebecca Scahill, New York, NY ★ Allison Smith, Union, CT ★ Seda Tierney, MD, Palo Alto, CA

This year’s NYC marathon was especially challenging, but running with The Marfan Foundation gave me so much motivation. It was so special to run in honor of my cousin, PJ, and whenever I wanted to give up, I thought of everyone who our fundraising and awareness e ff orts will benefit. ~ Rebecca Scahill

Running the NYC marathon with Team Victory was an incredible experience and the crowds were phenomenal. Throughout the entire course they were cheering us on until the finish line. ~ Seda Tierney, MD

I could not have trained nor crossed the finish line if it weren’t for Team Victory along with my friends and family who provided me with such comfort, support, and love during this incredibly grueling process. Being able to combine my love of running with raising awareness and funds for Marfan, Loeys-Dietz, and VEDS, a condition I myself live with, was truly magical. Race day brought about dozens of logistic curve balls for all runners; however, we all banded together to remind ourselves that we can do hard things. We each reminded ourselves what our ‘why’ was on running this race. This fueled our legs and souls to cross the finish line. I’m eternally grateful for the lifelong friendships I’ve made with Team Victory and look forward to seeing what we can do next! ~ Grace Ehrbar (Note: Grace has been running since the second grade. She worked with her treatment team and received approval to run/walk the marathon.)

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Medical Research Webinar Series Continues in 2023 Research continues to advance the knowledge on Marfan, LDS, and VEDS, in part due to the ongoing support of the Foundation’s research grant program. Through our Medical Research Webinar Series, we are bringing the latest in research news to our community. This webinar series provides the latest diagnosis and treatment information from the researchers themselves. Upcoming presentations cover genetics with Dr. Hal Dietz, Johns Hopkins; lungs with Dr. Enid Neptune, Johns Hopkins; and eyes with Dr. Je ff erson Doyle, Johns Hopkins, and Dr. Deborah Vanderveen, Boston Children’s Hospital. Each webinar is one hour and features a live visual presentation, followed by a Q&A session. Webinars can be accessed on a desktop, laptop, smartphone, tablet, or web enabled device. Or, you can simply dial in by phone and listen. Once you register for each webinar, you will receive a personal link for logging on. If you are unable to listen live, all recordings are available on our YouTube channel following the presentation. To register for one of these webinars, visit Marfan.org/ resources/educational-opportunities. To view recordings of past webinars, please visit our YouTube channel. Be sure to subscribe for alerts on new recordings as they become available.

February .............Marfan Awareness Month February 5 .........Walk for Victory, S. Florida (Hollywood) February 25 ......Walk for Victory, S. California (Costa Mesa) March 5 ...............Walk for Victory, Phoenix, AZ March 11 ..............Heartworks St. Louis March 11 ..............Walk for Victory, Houston, TX March TBD .........Walk for Victory, Atlanta, GA April 1 ..................Walk for Victory, Nashville, TN April 21 ................HeartWorks Chicago April 22 ...............Walk for Victory, North Carolina (Raleigh) April 22 ...............Walk for Victory, Milwaukee, WI May 5-7 ...............Camp Victory for Families May 13 ..................Walk for Victory, N. California (Aptos) June 3 ..................Walk for Victory, Boston June 10 ................Walk for Victory, Pacific Northwest (Seattle) June 11 .................Walk for Victory, Chicago SAVE THE DATE for Upcoming Educational Events April 15, 2023: New York Symposium on Marfan, Loeys-Dietz, and VEDS New York Academy of Medicine LEARN & CONNECT Join us for one or more of our upcoming events.

Enid Neptune, MD – LUNGS – March 29, 2023 7:00 pm Eastern

Hal Dietz, MD – GENETICS – February 23, 2023 7:00 pm Eastern

May 6, 2023: Michigan Regional Symposium Ann Arbor, Michigan

July 13-16, 2023: Conference | Chicago, Illinois

Learn More and/or Register u Events: Marfan.org/events u Walk for Victory: Marfan.org/walk u Conferences & Symposia: Marfan.org/ educational-opportunities

Je ff erson Doyle, MD, PhD, and Deborah Vanderveen, MD – EYES – May 2, 2023 | 7:00 pm Eastern

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We Support Your Kids!

The Foundation is here for your kids through our Kids Club, Camp Victory, conference programming, and more. Our Sydney Lerman Pediatric Hospitality Program brings joy to kids all over the country who are hospitalized or having surgery as a result of Marfan syndrome, Loeys-Dietz, or VEDS. Meet three children who were excited to receive gift packages from the Foundation during their recent hospital stays – Lillian from California, Camden from Utah, and Kevin from Ohio. The Sydney Lerman Pediatric Hospitality Program was started in 2017 by sisters Sydney and Carly Lerman of New York. Sydney, who is now a college student, endured many hospital stays throughout her childhood, including three months for a heart transplant and various hospitalizations for seven back surgeries. The sisters had a mission to let families who have a child in the hospital know that they are not alone and that the Marfan family is there for them. Through donations, this program provides a customized care package filled with goodies from coloring books and board games to local restaurant gift cards and other basic essentials to help them stay positive. The boxes are filled with loving and thoughtful gifts and shipped across the country. To learn more about this special project or if you know your child will be hospitalized and would like a gift box, visit Marfan.org/resources/ patients/lerman-program.

We LOVED our experience with this project. I was brought to tears by the generosity of the gifts. I loved being able to tell my son he isn’t alone with his health struggles. Thank you so much for this project! ~ Krystle, Camden’s Mom

My son has enjoyed the items, and it meant a lot to him to have the support of the Foundation. We lost many of our social supports during the pandemic, so the gifts were a bit of a life raft for him while waiting for his normal activities to resume. ~ Kelly, Kevin’s Mom Thank you so much! This gave Lillian LOTS to do as she adjusted to changes in her vision due to her eye surgeries and as she went through the appointments to get contact lenses and new glasses. The Lerman Project is doing awesome things for children! Thank you again! ~ Cathleen, Lillian’s Mom

Kudos to Christopher As we are coming upon Marfan Awareness Month in February, we want to recognize one teen who not only educated his school and community but also raised more than $15,000 for the Foundation last year. Christopher, whose brother, Charlie, has Marfan syndrome, wanted to do something to raise awareness about Charlie’s condition. So, he organized a fundraiser and walk at his school, going door-to-door, and asking for donations and explaining Marfan syndrome to his classmates. He was met with amazing support from his peers, business owners, and others who heard his story. Shortly after the walk, Christopher decided to explore more ways to get involved and keep his awareness e ff orts going - “I have no plan to slow down.” We can’t wait to see what Christopher does in 2023! There are many ways to get involved and make an impact! Explore our website to find the right fit for you.

p Christopher describes Marfan syndrome to his classmates

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