Research Studies

Mount Sinai Heart Center for Fibromuscular Dysplasia Care and Research

The prevalence, cause, prognosis and optimal treatment of fibromuscular dysplasia (FMD) is not known. Despite an improved clinical understanding of the disease, through initiatives such as the United States Registry for FMD, there has been little progress in understanding the biologic cause of FMD since its first description in 1938. Data from the registry suggests that many patients had subtle manifestations of FMD for years before diagnosis and treatment.

There are a number of similar features that occur in family members of patients with FMD.  This suggests that genetics play a significant role in the cause and/or predisposition for developing FMD.  

We have created “The Mount Sinai Heart Center for Fibromuscular Disease Care and Research” with the goal of determining the cause and full clinical spectrum of FMD.
 Our current research projects are listed below: 

  1. “Define-FMD” (Defining the Basis of Fibromuscular Dysplasia)As suggested by the name “Fibromuscular Dysplasia”, it is highly likely that fibroblasts play an important role in the development of FMD.  In the “Define-FMD” study, we take a small piece of skin from the upper arm using a punch biopsy under local anesthetic (similar to a dermatologist removing a mole).  From this skin, we are able to grow fibroblasts in the laboratory. The accompanying figure shows what fibroblasts look like after they grow in the laboratory.   This important study began in early 2013 and we are aiming to collect fibroblasts from up to 200 FMD patients. We also draw a small sample of blood to collect DNA and plasma. The plasma sample allows us to measure the level of different hormones and proteins in the blood, while the DNA gives us the ability to investigate possible genetic causes of FMD, which can be linked back to what we see in the fibroblast cells. This study will also use several other cutting-edge research techniques such as “proteomics” and “bioinformatics” in an effort to provide a better understanding of the cause of FMD.  Jason Kovacic, M.D., Ph.D. is leading this part of the FMD research.  He is an outstanding scientist and interventional cardiologist and is a faculty member in Mount Sinai Heart.  He has a particular interest in cell based therapies for the treatment of vascular disease.  Valentina d’Escamard will play a vital role in his lab for the processing of cellular and blood plasma procedures outlined above.
  2. Characterization of Carotid Artery Plaque in Patients with Fibromuscular Dysplasiaby Magnetic Resonance Imaging We have observed that a large number of patients with FMD have what appears to be a “plaque” on the carotid ultrasound.  This is unusual since the average age of at FMD diagnosis is about 52 years.  Manypatients with FMD have no or few cardiovascular risk factors. The aim of this study is to characterize the amount and nature of this material in the carotid arteries in patients with FMD using a high tesla research MRI.  Dr. Zahi Fayad is an international expert on MRI and vascular disease and he will be performing the MRI exams.  Our goals will be (1) to quantify the amount and composition of plaque (or whatever this material is) from FMD patients as compared to subjects without FMD (2) to identify the cardiovascular disease risk factor profile of FMD subjects versus those without FMD as it relates to the amount of atherosclerosis identified. This study will be restricted to FMD patients with medial fibroplasia (string of beads) who have never smoked.  Participants will undergo laboratory testing to assess kidney function prior to MRI imaging, and complete a clinical questionnaire.   The MRI exam involves three modalities to assess carotid 3D imaging, plaque components, and plaque vasculature requiring approximately 1.5 – 2 hour per imaging session. 
  3. Complete Phenotypic Description of Patients with FMD
    We have developed an electronic database for all of our patients with FMD.  This is a much more detailed database than we are able to collect in the FMD registry and will allow us to answer a number of questions that have arisen from the information gleaned from the U.S. Registry for FMD.  We will follow our patients over time and survey their medical progress, with the goal of learning how FMD behaves clinically over time and prospectively determine the natural history (clinical course) and results of therapy in FMD patients.   The major strength of this approach is that we will be able to examine how biologic and genetic aspects of FMD translate into clinical manifestations of FMD. 
  4. United States Registry for Fibromuscular Dysplasia – Enrollment Site
    The Mount Sinai Medical Center in New York, NY is one of eleven enrollment centers in the nation.  Dr. Jeffrey W. Olin is the principal investigator for this study and we will continue to work hard to enter all new patients into the registry.   

FMD Team

  • Jeffrey W Olin, D.O.- Director, Mount Sinai Heart Center for FMD Care and Research.
  • Daniella Kadian-Dodov, MD - Vascular Medicine, Vascular Laboratory and Vascular Medicine Research
  • Jason Kovacic, M.D., Ph.D.  Principal Investigator of the Define FMD project.  
  • Valentina d’Escamard MSc- Technical Assistant, Dr. Kovacic’s lab.  
  • Peter Faries, M.D. – Chief Division of Vascular Surgery
  • Zahi A. Fayad, Ph.D.-  Director, Translational and Molecular Imaging.  
  • Susan Gustavson, R.V.T.- Technical Director, Vascular Diagnostic Laboratory
  • Annette King, NP- Clinical Research Coordinator
  • Robert Lookstein, M.D. – Chief Interventional Radiology
  • Michael Marin, M.D. – Chair, Department of Surgery
  • Aman Patel, M.D. – Chief Neuro-intervention and Vice Chair Department of Neurosurgery
  • Valentin Fuster,M.D.,Ph.D.- Director Mount Sinai Heart, Physician-in-Chief, Mount Sinai Hospital.    

 If you are interested in learning more about the studies outlined above, please contact Dr.’s Jeffrey W. Olin and Daniella Kadian-Dodov at the Mount Sinai Medical Center (emails listed below).

Jeffrey W. Olin, DO                  jeffrey.olin@mountsinai.org
Daniella Kadian-Dodov, MD        daniella.kadian-dodov@mountsinai.org

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University of Michigan

Santhi K. Ganesh, MD and colleagues at the University of Michigan are conducting research on the genetic basis of arterial dysplasia. If you agree to participate we will gather pertinent information from you or your medical records, and you will be asked to provide a blood sample. We are also interested to know if any of your family members have been affected by FMD, and we may ask for your assistance in contacting  family members who may or may not have FMD for participation in this study. Details of the study may be obtained by emailing Dr. Ganesh at:sganesh@umich.edu. For more information, click here

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NIA Clinical Study

The purposes of this study are to identify the genes responsible for inherited connective tissue disorders and learn about the range of medical problems they cause. It will investigate whether specific gene changes cause specific medical problems and will establish diagnostic criteria (signs and symptoms) for the individual syndromes.

Children and adults with a known or suspected inherited connective tissue disorder (Marfan, Ehlers-Danlos or Stickler syndrome, or other closely related disorders) and their family members may be eligible for this study.  Even though not stated, FMD patients are being considered/accepted for this study.  For more information click here.

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Fibromuscular dysplasia (FMD) Registry in France

We seek partnership with patient organizations. To my knowledge however, there exists no FMD patient association in Europe.  This is why I am keen to have contacts with patients who could be interested in a European FMD initiative and would eventually attend our forthcoming FMD meeting (November 8th in Paris).

Written by Pr. Pierre-François Plouin, June 2013

ARCADIA (Assessment of Renal and Cervical Artery DysplasIA) is a French registry designed to document phenotypic and genetic traits in patients with renal and/or cervical artery fibromuscular dysplasia (FMD). PROFILE (PROgression of FIbromuscular LEsions) is a cohort study evaluating the progression of FMD lesions. These studies are coordinated by the hypertension unit and the reference center for rare vascular diseases at Hopital Europeen G Pompidou, Paris, France (http://www.maladiesvasculairesrares.com).

Objectives

The main objective is to create a National FMD registry to collect standardized information from consenting patients diagnosed with the condition in 16 participating centers. The first application is the assessment of the frequency of multi-site FMD, i.e. the frequency of cervical artery FMD in patients presenting with renal artery FMD and vice-versa (ARCADIA and PROFILE). The second application is the assessment of the incidence and risk factors for progression of FMD lesions (PROFILE). The third application is case-control study to identify susceptibility genes for FMD, including genes that may influence disease progression or be associated with complications.

Overall design

Patients are eligible if (a) they have renal or cervical artery FMD with either the string-of-beads sign (‘medial’ or multifocal FMD) or focal/tubular lesions (focal FMD) at CT-angiography, MR-angiography, or intra-arterial angiography; (b) they give informed consent to provide leukocyte DNA for analysis and for the collection of pertinent bioclinical and morphologic annotations. In addition to DNA sampling and collection of cross-sectional information, patients who are available and willing to undergo a 3-year follow-up are offered the possibility to enroll in the PROFILE cohort. Phenotypic assessment, follow-up and indications for revascularization comply with current recommendations and best clinical practice. Patient participation lasts one day for ARCADIA, and 3 years for PROFILE.

Expected results

The natural history of the condition will be better characterized, allowing development of optimal strategies for investigating, monitoring, following-up and treating patients with FMD. The biological and genetic study should help improve understanding of the pathophysiology and genetic determinism of this rare disease and open new possibilities for therapy.

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Fibromuscular Dysplasia Biorepository

In collaboration with the Cleveland Clinic and Mayo Clinic, a research study is being conducted to:

  1. Identify genetic factors that may influence susceptibility to certain vascular diseases like FMD so that we can find new ways to its prevention, diagnosis and treatment;
  2. Investigate the prevalence of traditional cardiovascular risk factors in individuals and family members with FMD.


For anyone attending the Annual FMDSA Meeting in Cleveland, we would like to invite you to participate in this study if you have not already done so at the 2010 or 2011 conferences. Any patient with FMD is welcome to participate. First-degree family members of FMD patients (such as parents, siblings, and adult children) may also volunteer to participate if they wish.

If you agree to participate in this study, it will involve giving your consent, completing a medical and FMD questionnaire, obtaining your vital signs, and collecting a sample of your blood.

There will be two opportunities for you to participate in this study:

  1. You may schedule an appointment with research personnel at the Cleveland Clinic during the week of the meeting. You do not need to be a Cleveland Clinic patient to participate in this study or to schedule an appointment with the research staff. To schedule a research appointment, please contact Neil Poria at (216)-444-0334.
  2. Research staff will be available during the FMDSA meeting at the conference’s designated lunch break.

If you wish to obtain more information about this study, please feel free to contact Dr. Heather Gornik at:gornikh@ccf.org, or Neil Poria at: 216-444-0334. To view the Mayo Clinic information brochure, please click here

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Update from Marja Wessels, the Netherlands

Dr Marja Wessels (MD, PhD), clinical geneticist, Dr Rob Willemsen (PhD)
and Prof J Kros (MD, PhD), pathologist at the Erasmus Medical Center
Rotterdam, The netherlands are continuing their work on histopathology
studies including immunostaining for TGFB pathway components to describe
in more detail characteristics of FMD pathology. We hope to finish these
studies by the end of this year (2011)

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Orphanet

Orphanet is led by a European consortium of around 40 countries, coordinated by the French team. National teams are responsible for the collection of information on specialised clinics, medical laboratories, ongoing research and patient organisations in their country. For information on research, clinical trials and resources in other countries, please click here