Cure HHT Blog
The Cure HHT blog is now linked through the Cure HHT website! Simply click on the "Blog" button at the top of the website homepage to see all of the stories posted since the blog's inception in 2016.
The Cure HHT blog is just another awareness avenue for patients, doctors, supporters and organization members to share stories, videos and pictures with the world and each other. And, of course, for Cure HHT to keep you updated on what's happening in the world of HHT and how those things relate to you.
We would love to have more of the community step up to contribute. This is how you create change – it only takes one voice to spark a hundred, and then a thousand and then a million.
Will you be that voice for Cure HHT?
Get involved and stay empowered. Contact [email protected] to become a Cure HHT blogger.
Hosting our First Blood Drive for HHT Awareness!
She wanted to give blood by the end, but she didn’t meet the weight requirement 😉
Since marrying into an HHT family, I have felt a need to do more to advocate for my family members, raise awareness, and help in any way I can. I know how precious both money and blood can be to this community, but we are not always in a financial position to give to the foundation (although every little bit really does count!). I decided to reach out to the local Red Cross and my church to coordinate a blood drive. I’d like to talk about this process, how surprisingly easy it can be, and tell you how everything went on the big day!
- Reaching out to your local American Red Cross representative
- You can Google this, or look it up on the Red Cross website: redcrossblood.org
- In my first e-mail, I told my rep, Kristi, about HHT and how I felt like I wanted to do more to help raise awareness. I offered my assistance to volunteer with local blood drives and asked her how I could learn to coordinate one of my own.
- She was SO NICE! Y’all – seriously, reach out to your local Red Cross folks – even if you don’t want to host a blood drive, just get to know them as your friend. I have never met anyone in this business I haven’t liked. They truly have a heart and soul for service.
- Bringing awareness through an ‘In Honor of’ blood drive
- Kristi told me about a campus-wide blood drive happening where I work at Kansas State University. While this drive was already planned and ready to go, they wanted to feature HHT to help bring awareness to the disease and the potential need for blood in the community because of it.
- If you aren’t ready to coordinate your own blood drive, you can certainly raise awareness about HHT by making an already scheduled blood drive in honor or in memory of someone.
- I filled out a form talking about my family, the disease, and our experiences with blood donation in the past. My husband and daughter have yet to receive blood transfusions, but my mother-in-law has and her father was reliant on them during the last years of his life.
- The Red Cross and the campus newspaper did a short interview and press release detailing HHT and the need for blood in the HHT community.
- Coordinating your own drive
- If you are ready to host and coordinate your own blood drive, I would suggest getting these things in line:
- A location
- A few potential dates
- A few volunteers to help schedule appointments/make signs/send reminder e-mails and calls/help on the day of the drive
- Once you have an idea of the above information, tell your Red Cross rep you are ready! They will let you know what dates work best for their schedule and they almost literally do the rest!
- Once we settled on a day that worked well for the church, Kristi told me what time, how many appointments we would have, and what to do every step of the way.
- We started with a small drive – 2 Red Cross workers and 21 appointment slots. The drive went from 9am to 3pm this last Sunday.
- Advertising your blood drive
- Since we were having our blood drive at church, I asked the pastors if I could speak about HHT and the reason behind this blood drive during church service. They were more than happy to oblige and I just gave a quick 2-3 minute synopsis of HHT and why giving blood is so important, especially to those with diseases like HHT.
- Kristi had already given me a sign-up sheet and reminder cards for donors. I set up a table in our church’s gathering place to book appointments, and I had almost every appointment booked by the end of that same church day!
- Kristi had also given me some table toppers with information about the drive, flyers, and contact information sheets. They literally take care of everything!
- Preparing for the drive
- A few days before the blood drive, I entered everyone’s information into the Red Cross system. Blood drive coordinators get their own login so you can access appointment times, schedule donors, and send e-mails. All the flyers, advertisements, and resources are also available on the site.
- Everyone was sent an automatic reminder e-mail about their appointment.
- I asked my church group to volunteer to make goody bags for the donors. (Since this was a small drive specifically to raise awareness about HHT, I wanted to hand out some HHT information and some treats to donors as a thank you.)
- Blood drive day
- I arrived at the church at the same time as the Red Cross staff to help see them into the building.
- They have everything so organized – the only thing I did was move around some chairs! They had their own tables, music, fans, water, food, and of course all the donation supplies.
- I stayed at the drive to greet donors as they came in, to guide them to the sign-in sheet, and then I just chatted with them as they waited for their appointment! My job was by far the easiest!
- At the end of the day, the staff packed everything up and went on their way! They were so nice and made every donor feel special and well taken care of.
Our first blood drive was a success and we met our blood donation goal! It really was surprisingly easy to coordinate and everything went really well! The Red Cross did 90% of the work, I really just found a venue and advertised it. I can’t wait to host another this fall! We are hoping to make this happen at our church every two months. This way, regular donors can continue to come back when they are eligible to give (after 56 days for a whole blood donation). If anyone has any questions about this process, let me know or reach out to your local Red Cross people!
Eleanor at her desk, supervising the blood drive. 🙂
She wanted to give blood by the end, but she didn’t meet the weight requirement 😉
Goody bags for blood donors with HHT information
Goody bags for blood donors with HHT information
Cure HHT Launches 22nd Center of Excellence
22nd HHT Center of Excellence in North America
University of Chicago Medicine HHT Center
“We are delighted that HHT multidisciplinary care will now be a reality in Chicago and the surrounding states,” said Cure HHT Executive Director Marianne Clancy.
The University of Chicago Medicine is the only facility in Illinois that specializes in the diagnosis, evaluation and treatment of HHT. This newest HHT Center of Excellence features a multidisciplinary team, led by Dr. Issam Awad, which coordinates care for adult and pediatric patients. Whether a patient needs genetic screening or a complex procedure, Dr. Awad’s team of specialists has the knowledge, resources and expertise to provide advanced and comprehensive care.
Dr. Awad is an internationally recognized leader in neurosurgery. As the John Harper Seeley Professor of Surgery, and Director of Neurovascular Surgery at The University of Chicago Medicine, he specializes in surgical management of neurovascular conditions affecting the brain and spinal cord, including 30 years of experience with managing HHT related problems. Dr. Awad is looking forward to a fruitful and contributive partnership with Cure HHT and the HHT patient community.
Dr. Umesh Dyamenahalli, Associate Medical Director
Dr. Awad Issam, Medical Director
Medical Director: Issam Awad, MD, MSc, FACS
Program Coordinator: Shannon Love, RN, BSN
Make an Appointment: 773-702-4452
HHT Specialties at U Chicago Medicine:
Cure HHT Welcomes New Board Members
Join us in Welcoming Alyson Conger, Sara Palmer and Jim Lapides!
We are pleased to announce the appointment of Alyson Conger, Sara Palmer and Jim Lapides to the Cure HHT Board of Directors, a role dedicated to guiding the global foundation toward new levels of awareness and finding a cure for HHT.
"I have personally watched the growth of the foundation since my childhood as my parents have been involved since the beginning. Our family has suffered great tragedies with the disease, but I have experienced firsthand the progress in screening, treatment and awareness for HHT patients. I look forward to being part of the movement for a cure and continued advances to benefit my children, grandchildren and the entire HHT community." Alyson Conger, Provo, UH
"Joining the board is way to deepen my involvement and work closely with other committed volunteers to improve education and awareness as well as to support research that leads to better treatments for HHT. My hope is Cure HHT can increase the rate of diagnosis; help develop drugs and other non-invasive treatments; and, ultimately find a cure for HHT.” Sara Palmer, Baltimore, MD
“I am fighting for a better life for me, my family and everyone else who suffers from this disease. Our organization and science are ready for a major leap forward, and we are closer to a cure than ever before.” Jim Lapides, Brookline, MA
> Full Board List
Continuing Medical Education
HHT for Clinicians at the 17th National Patient and Family Conference
CME Evaluation Form - Attendees who registered to receive continuing education credit need to print, complete and email the CME evaluation form to [email protected] by August 27, 2014. A certificate will be issued upon receipt of this documentation.
July 18-20, 2014
Santa Clara, California
Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu Syndrome, is a potentially life-threatening genetic disorder that, if properly diagnosed and treated, can be managed and tragedies can be averted. This program is designed for medical professionals who are likely to encounter HHT patients, among them: internal medicine, otolaryngology, gastroenterology, cardiology, interventional radiology, neurology, genetic counseling and nursing.
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the Academy for Continued Healthcare Learning and HHT Foundation. The Academy for Continued Healthcare Learning is accredited by the ACCME to provide continuing medical education for physicians.
ACHL has been accredited as an Authorized Provider by the International Association for Continuing Education and Training (IACET). ACHL is authorized by IACET to offer 1.3 CEUs for this program.
Provider approved by the California Board of Registered Nursing, Provider Number 14803 for 12.4 contact hours.
Credit Designation Statement
ACHL designates this educational activity for a maximum of 15.5AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Upon conclusion of this conference, participants will be able to:
- Define the diagnostic criteria for HHT
- Identify treatment options for Pulmonary and Cerebral AVM
- Identify treatment options for Epistaxis
- Identify treatment options for Gastrointestinal and Liver AVM
- Discuss new potential therapies for the management of refractory HHT complications
Download the Conference Brochure
CDC Conference: HHT in the 21st Century
March 5-6, 2008
The Hereditary Hemorrhagic Telangiectasia (HHT) Foundation International, in conjunction with the Center for Disease Control and Prevention (CDC), held a landmark conference on March 5 – 6, 2008 at the Tom Harkin Global Communications Center in Atlanta, Georgia.
The purpose of this conference was to define and prioritize objectives to improve clinical outcomes, enhance the quality of life for those affected by HHT, and reduce intrinsic and extrinsic costs related to HHT treatment.
Please click on the following links to learn more about the Conference:
Over 60 health care professionals including: emergency medicine physicians, school nurses, family practitioners/internal medicine, pediatric specialists, physician assistants, dentists and dental hygienists, dermatologists, gastroenterologists, otolaryngologists, hematologists, pulmonologists, neurologists, cardiologists, radiologists, geneticists as well as representatives from governmental and non-governmental organizations attended this national conference. You can view participants by clicking on Participant List.
HHT is a long neglected national health problem that affects 75,000 Americans. HHT is a multisystem vascular genetic disorder producing arterioveneous malformations in the brain and lung which may result in stroke or hemorrhage. Twenty percent of children and adults with HHT die prematurely or may become disabled due to lack of recognition by the medical community. These outcomes are largely preventable with proper intervention. Timely diagnosis and treatment of HHT could improve outcomes and quality of life for people living with HHT while eliminating $6.6 billion in avoidable health care costs.
The conference was the first step in addressing this national health issue by identifying outreach programs that will increase surveillance, increase early recognition of people affected with this genetic condition, and support life saving interventions
For more information, contact Marianne Clancy, Executive Director of the HHT Foundation International, at 800-448-6389 or email her at [email protected] .
Our achievements in these areas during 2003-2006 were possible largely thanks to the support and generosity of our members and from grants received from John Abele on behalf of The Argosy Foundation.
NIH Workshop - HHT Vascular Biology & Pathophysiology
June 8-9, 2006
HHT Foundation in conjunction with the National Institute of Health (NIH) sponsored an HHT Workshop for basic scientific research. The conference provided an opportunity for NIH to formulate an HHT research plan. The workshop included a mix of keynote talks, platform presentations, and open discussion on several themes, including:
- Transforming Growth Factor-Beta Pathway and HHT
- Endothelial Biology and HHT
- Vascular Biology and HHT
- Chemical Genomics and HHT
- Organ Pathophysiology in HHT
- Click on the link below to view the Overview of the Program:
Clinical Practice Guidelines for HHT
November 15-16, 2006
The Consensus Development Conference consists of a group of experts in the field of HHT brought together to work collaboratively with professional facilitators to improve diagnosis and treatment of HHT. The goals of the conference are to review existing evidence on specific medical issues in a systematic fashion, to obtain expert consensus where scientific evidence is lacking, and to synthesize recommendations for Practice Guidelines
- To revise the existing Clinical Practice Guidelines for the diagnosis of HHT (Curacao Criteria) by incorporating the utilization of molecular genetic testing.
- To develop Clinical Practice Guidelines for the diagnosis, screening, and treatment of the major areas of clinical concern in HHT, including chronic epistaxis (nosebleeds), pulmonary arteriovenous malformations (AVMs), hepatic vascular malformations, cerebral AVMs, gastrointestinal bleeding, and skin telangiectases.
- To develop materials for and approaches to dissemination of the Clinical Practice Guidelines for health professionals. Examples include peer-reviewed publications, a site on the HHT Foundation International web page, and a multimedia presentation that would be available to individuals or educational and training programs that wish to teach about HHT.
- To develop recommendations for research priorities that will continue to improve the quality of evidence upon which the Clinical Practice Guidelines are based
At the conclusion of the Consensus Conference, the following will be identified and established:
- Clinical and genetic criteria by which a definitive diagnosis of HHT can be made
- Criteria for diagnosis and treatment of the most common symptoms and organ manifestations of HHT, including chronic nosebleeds, GI bleeding, pulmonary and cerebral AVMs, and liver vascular malformations.
- Protocols for routine follow-up by primary care and specialty physicians.
- Protocols for treatment of acute episodes.
- Recommendations for publication and broad distribution of Consensus findings and HHT Standard Practice Guidelines, and presentation at scientific and professional symposia.
- Strategies developed for implementation of the Practice Guidelines as the standard of practice and for assessment of the impact of Practice Guidelines on physician behavior and HHT care in North America.
2004 Research Grant Recipients
Treatment of Disease
Laser Treatment for Nosebleeds: When Is It Likely to Work?
Elizabeth J. Mahoney, M.D.
Stanley Shapshay, M.D.
"New classification of nasal vasculature patterns in hereditary hemorrhagic telangiectasia". American Journal of Rhinology. Volume 20, Number 1. January-February 2006.
Over the years, a wide variety of treatments have been used to help manage nosebleeds in HHT patients including electro-cauterization, nasal packing, septodermoplasty (see article herein), arterial embolization, arterial ligation, and hormone therapy. While many of these interventions have achieved moderate success in the management of the HHT patient's nosebleeds, recent attention has focused on the use of lasers for the treatment of intranasal telangiectases in patients with HHT.
Finally, patients responses to therapy were evaluated.Patients were identified as a responder to the Nd-YAG laser treatment if they noted a 50% decrease in the severity and frequency of their nosebleeds for a period of greater than 6 months.
Interestingly, vascular pattern I was most common, while vascular pattern III was least common. Patients with vascular pattern I uniformly demonstrated a good response to the Nd-YAG laser. Conversely, nearly all of the patients with vascular pattern II were poor responders to the Nd-YAG laser treatments. Finally, 80% of patients with pattern III demonstrated a good response to the Nd-YAG laser photocoagulation treatment.
In addition to correlating vascular pattern with response to Nd-YAG laser photocoagulation, vascular pattern classification was also correlated with disease severity. Patients with vascular pattern I tended to be most mildly impacted by HHT, while patients with vascular pattern II were more severely impacted. Those with pattern III were more broadly distributed over the range of disease severity.
These findings are important for physicians caring for HHT patients as they may help to predict response to laser therapy. For example, when a patient with HHT is noted to have isolated intranasal telangiectases, he or she can be counseled to anticipate a good response to Nd-YAG laser photocoagulation, while patients with a more diffuse vascular pattern almost uniformly have a sub-optimal response to their Nd-YAG laser treatments. For patients with patterns I and III, treatment with the Nd-YAG laser will typically provide an improvement in the intensity and frequency of epistaxis for a minimum of six months. The procedure is simple, requires only local anesthesia with sedation, and has few risks or side-effects. To conclude, the findings in this study will allow otolaryngologists to better counsel HHT patients and improve stratification for therapy.
2005 Research Grant Recipients
Mechanism of Disease: $50,000 Research Grant
Primary Cultures of Endothelial and Monocytic Cells Derived from HHT Patients: An Open Window to Unravel the Pathogeniticy of HHT
Carmelo Bernabeu, PhD.
Centro de Investgaciones Biologicas, CSIC, Madrid, Spain
Blood vessels are lined with endothelial cells that express two proteins known as endoglin and ALK-1. Mutations in endoglin or ALK-1 genes interfere with the expression and function of these proteins in endothelial cells, affecting the vessels network and giving rise to the Hereditary Hemorrhagic Telangiectasia (HHT). Thus, isolation of endothelial cells derived from HHT patients to determine endoglin/ALK-1 levels and activity is crucial to understand how the disease develops. So far, most of the studies have been carried out in endothelial cells from umbilical veins of affected newborns. However, since the prevalence of HHT increases with age, probably these newborn endothelial cells are not a good model system. Instead, endothelial cells from adult patients with known HHT symptoms would be a more appropriate model of choice. In this project, we propose to isolate and characterize endothelial cells derived from blood samples of HHT patients. The same samples will be used to isolate the blood cells called monocytes, which have been shown to express endoglin, although at lower levels than endothelial cells. Both cell types will be used to determine whether the levels and function of endoglin and ALK-1 are affected in HHT patients and whether there is a correlation between these properties and the severity of the disease in the individual patient. Also, the impact of endoglin or ALK-1 mutations on endothelial gene expression using microarrays, will be assessed. These studies may help to understand the mechanisms of the disease, as well as to design new diagnostic methods.
Outcomes: According to Dr. Bernabeu, "Blood vessels are lined with endothelial cells that express two proteins known as endoglin and ALK-1. Mutations in endoglin or ALK-1 genes interfere with the expression and function of these proteins in endothelial cells, affecting the vessels network and giving rise to Hereditary Hemorrhagic Telangiectasia (HHT).
We have isolated and characterized for the first time, circulating endothelial cells derived from blood samples of HHT patients. These cells show functional abnormalities that may explain the vascular lesions of those with HHT. To further investigate the altered function of these cells, we have analyzed the changes in their gene expression pattern (a sort of fingerprint of the cell). This study has allowed the identification of several genes specifically modified in endothelial cells from HHT patients. The genes affected are involved in different cellular processes relevant to the generation of the vascular lesion. Overall, these represent pioneer studies on the establishment of a culture method to isolate endothelial cells derived from HHT patients. Further studies on the genetic fingerprint of these cells will help to explain the molecular mechanism of the disease, which in turn may contribute to the design of novel therapeutic approaches to cure the disease.
Once a culture method to isolate endothelial cells derived from HHT patients is established, this method can be reproduced by other laboratories and these cells can be used for further biochemical and functional analyses. In addition, studies on the specific genes whose expression is affected in HHT cells are necessary. It is crucial to understand why these genes are disregulated and how the protein’s function is affected in the HHT cell.
This study constitutes a solid base to apply for a larger grant. In fact, at the end of this year, I will apply for a three- year grant on an HHT related subject to the Spanish Ministry of Education and Science for a total amount of approx. $300,000 USD.”
Treatment of Disease: $50,000 Research Grant
Identification of Risk Factors for AVM Formation in HHT
Douglas Marchuk, PhD
Although mutations in one of two genes, endoglin and ACVRL1, cause HHT, questions pertaining to vascular lesion formation in HHT remain largely unanswered. These vascular lesions in HHT develop in discrete locations, and often increase in number and size with age. The focal nature of these lesions and their age-dependent appearance suggests that yet undiscovered “factors” initiate lesion development. The identification of these initiation factors could lead to new approaches and therapies to reduce the incidence of vascular lesion formation.
According to Dr. Marchuk, "My laboratory has recently shown that older mice heterozygous for an engineered acvrl1 mutation show many features of the human HHT phenotype. Using a genetic approach, we will cross the ACVRL1 mutation into various genetic backgrounds that will enable us to test specific hypotheses concerning the nature of the initiation factor(s) for lesion formation. These genetically sensitized backgrounds are mutant mice that exhibit various potential physiological triggers for lesion formation, including (1) local alterations in blood pressure, (2) hypoxia of the surrounding tissue, (3) local inflammation of the endothelium, or (4) a second somatic mutation in the wild-type copy of the gene."
One (or more) of these sensitized genetic backgrounds may show an increase in AVM formation, lending further support for that particular trigger for lesion formation. Some of these physiological triggers can be reduced by currently-available pharmacological treatments, lending some hope of a long-term treatment outcome from this work. In addition, this work may lead to a more highly-penetrant animal model for HHT for further investigation into the mechanisms of HHT pathogenesis.
Outcomes: Despite the discoveries of the HHT genes, many questions remain unanswered concerning the role of these genes in the pathogenesis of HHT. The most critical question is an explanation for the focal nature of the vascular lesions associated with this disorder. Germline mutations only predispose the individual to the development of the discrete focal vascular lesions. The aim of our proposal was to identify the “trigger(s)” for vascular lesion development.
Various hypotheses have been proposed to explain the actual trigger for lesion development. These include:
- Elevated Blood Pressure (cross with Agt tg and eNos null mice)
- Tissue Hypoxia (cross with Csf2 and EpoR null mice)
- Local Inflammation (cross with IL2 and IL10 null mice) d. Loss of Heterozygosity at Acvrl1 (Cross with p53 null and Blm hypomorph mice)
According to Dr. Marchuk, “We did not find that loss of eNos, IL10, or p53 greatly exacerbated the phenotype of HHT mice. But we can say with some confidence that in the existing HHT mouse models, these various triggers do not appear to be the limiting factor in causing the HHT lesions. After performing the initial crosses to create the appropriate mutant mice, we began aging the mice. Here again we chose the 6 month end point to examine the mice. This final cross is ongoing and we have thus far analyzed only 9 of the double mutant mice. However, we are cautiously excited about our initial results with this cross. In about 1/3 of the mutant mice, we have found grossly dilated vessels on the surface of the liver. We have seen this level of dilation occasionally before, but we have never routinely seen this phenotype in HHT mice at such an early age."
Dr. Marchuk's team is deeply grateful for this funding from the HHT Foundation which made their work possible. "We hope sometime in the future to leverage your investment in our work with a funded NIH grant proposal to continue our work on identifying the trigger for vascular lesion formation in HHT.”
2006 Research Grant Recipients
At the groundbreaking National Institutes of Health (NIH) HHT meeting in June 2006, it was our pleasure to award two new HHT research grants. There had been an extensive peer review of ten proposals. The two winning projects were:
Mechanism of Disease $50,000 Research Grant Award
TGF-B Activates eNOS and Regulates Vasomotor Function by an endoglin-and Alk-1' Dependent Mechanism
Dr. Michelle Letarte
Toronto Hospital for Sick Children, Canada
According to Dr. Letarte, “The genes mutated in HHT are endoglin and ALK1. The products of these genes, the endoglin and ALK1 proteins, are receptors for a potent factor called TGF-ß. We now have recent evidence that this TGF-ß factor may control the dilatation of blood vessels. We hypothesize that this normal process of regulation of vessel dilatation by TGF-ß is defective in HHT and can eventually lead to the clinical manifestations of disease. We will use the mouse models of HHT1 and HHT2 and test blood vessels isolated from these mice to see how they respond to TGF-ß compared to those of normal mice. We will then identify the molecules and pathways responsible for the effects of TGF-ß in cells from mice and patients with HHT. Our experiments should provide a better understanding of the mechanisms responsible for the early events in the disease and pave the way to novel therapeutic interventions.
Our specific objectives are:
- To measure the effects of TGF-b1 on eNOS-dependent vasodilation in small resistance arteries isolated from Eng+/- (HHT1 model) and control mice, using a perfusion myograph.
- To test whether TGF-b1 regulation of eNOS-dependent vasodilation is similarly altered in HHT2. Vasodilation will be measured on small resistance arteries from alk1+/- and control mice.
- To characterize the mechanism of TGF-b1-induced eNOS activation in murine endothelial cells (normal and deficient endoglin) and in human umbilical vein endothelial cells (HUVEC) from newborns with a molecular diagnostic of HHT1 or HHT2. We will measure the effects of TGF-b1 on eNOS enzymatic activity, eNOS-Hsp90 association, and eNOS phosphorylation using specific anti-phospho-eNOS antibodies. We will test for the association of ALK1 with eNOS and/or Hsp90 and see if its overexpression in endothelial cells amplifies the activation of eNOS by TGF-b1.
Dr. Letarte states, “We are very grateful to the HHT International Foundation for awarding us this grant and thank all of you for your kind donations. Our daily efforts are devoted to understanding the underlying mechanisms of HHT through basic research. We could not do it without your generous financial and moral support.”
Treatment of Disease $50,000 Research Grant Award
Differentiation of Eng-/- Embryonic Stem Cells in Embryoid Bodies, a Paradigm for Vascuaogenesis/Angiogenesis
Defects in HHT and a Potential Drug Screen
Professor Christine Mummery
Utrecht, The Netherlands
This study will examine the effects of Thalidomide on blood vessel structure. According to Professor Mummery, “By studying the effects of thalidomide on vessel stabilization, we propose (1) to validate the Eng-/vasculogenesis/angiogenesis assay as a useful method in screening potential HHT drugs, particularly those directed towards improving vessel robustness and (2) to determine the mechanisms underlying vessel stabilization. We will attempt to generate a human model of HHT development in vitro.”
(1) Mechanism underlying vessel stabilization. By using FACS sorting, ECs and SMCs will be isolated from 18 day Eng-/- EBs treated or otherwise with thalidomide. Transcriptional profiles will be compared both by microarray analysis and by real time RT-PCR to identify signaling pathways that may underlie the effects observed.
(2) Validation of the EB vasculogenesis/angiogenesis assay for screening HHT drugs. To date our experiments have been performed using only one of each wt, Eng+/- and Eng-/- ES cell lines. To validate our model, multiple new mES cell lines lacking or heterozygous for endoglin will be generated from blastocysts isolated from Eng+/- crosses and EB differentiation in presence of thalidomide will be repeated.
(3) Since we have expertise in the differentiation of multiple human ESC (HESC) lines into mesoderm derivatives, including vascular cells, in EBs we will test the effects of thalidomide in an analogous model to validate and extend our findings on vessel stabilization to human. Time permitting and the context of other studies to optimize siRNA-mediated knockdown in HESCs, we will attempt to generate a human model of HHT development in vitro.
OUTCOMES published in Nature Medicine
2007 Research Grant Recipients
David and Clara Bartley Jordan Epistaxis Research Grant Award
Development of a Standardized Epistaxis Severity Score (ESS) in HHT in Order to Validate Therapy Efficacy
Dr. Jeff Hoag
Johns Hopkins University School of Medicine and Drexel University School of Medicine
This study is awarded to Dr. Jeffrey Hoag of Drexel University School of Medicine and will develop a uniform epistaxis severity scoring system. This system will be used to assess the effectiveness of specific treatments for HHT-related epistaxis. HHT-Epistaxis Severity Scores will help to validate current treatment algorithms, and serve as a benchmark for the development of future medical and surgical treatment strategies. The study will involve a population of 245 participants with a varying range of epistaxis severity which will provide an adequate representation of the population of patients with HHT-related epistaxis.
Specific Aim 1: The study will try to determine the factors associated with epistaxis in HHT. A standardized list of patient perceived important variables combined with provider perceived important variables will provide a comprehensive list of factors associated with HHT-related epistaxis. This list will be developed with patient care providers from HHT Centers of Excellence and Patient Focus Groups through the support of the HHT Foundation International.
Specific Aim 2: (Epistaxis Severity Score) This study will develop a uniform epistaxis severity scoring system.
Specific Aim 3: To validate the HHT-Epistaxis Severity Score through correlation with standardized quality of life (QOL) assessments and statistical models.
Specific Aim 4: (Assessment of Epistaxis Treatment) To use the HHT-Epistaxis Severity Score to assess the effectiveness of specific treatments for HHT-related epistaxis. HHT-Epistaxis Severity Scores will help to validate current treatment algorithms, and serve as a benchmark for the development of future medical and surgical treatment strategies.
Outcome: Dr. Hoag presented his research at the HHT Scientific Meeting held in Santander, Spain in 2009 and published his findings in the April 2010 edition of Laryngoscope. The Epistaxis Severity Scoring Tool developed by Dr. Hoag is used by ENT's at HHT Treatment Centers around the world to determine severity of nosebleeds and improvements realized from laryngology treatments, including the 2011 NOSE Study.
ESS Published Article - Laryngoscope 120: April 2010
Epistaxis Severity Scoring Tool (ESS)
This study was made possible through a generous donation from David and Clara Barley Jordan and many other HHT Foundation members who made donations to the HHT Epistaxis Fund.
Mayo Clinic Team Leverages $50K HHT Foundation Research Award to $1 Million
Dr. Karen Swanson, D.O., Director of the Mayo Clinic HHT Center
Dr. Swanson has been approved for funding from the Office of Orphan Products Development within the Food and Drug Administration (FDA) for an interferon protocol. Dr. Swanson's budget is now $1 million over three years. The study, entitled "Interferon-2B Treatment in Hereditary Hemorrhagic Telangiectasia," was directed towards determining whether interferon may provide a safe and effective treatment for HHT. A certain type of interferon has already been shown to have anti-angiogenic properties and is currently used in the treatment of infantile hemangiomas and liver hemangiomas. Both of these are diseases of abnormal blood vessel formation similar to the teleangiectases and AVMs that occur in HHT. To everyone who donated generously to the HHT Foundation so that we could provide that initial $50,000, without which the larger grant would never have been approved, we offer our wholehearted thanks on behalf of all of those with HHT.