Lymphedema has accurately been called the "orphan" disease as such little research has historically been undertaken to understand both the pathophysiology of the condition and research that could possible lead to a cure. Despite the fact that funding is still limited compared to other conditions, the pace of research has dramatically quickened in the past few years.
Progress has been made in understand the condition by research into how the lymphatic system ties into other diseases and body systems. The end result thus far has been a tie in that no one would have expected and that the lymphatic system is deeply and intrinsically connected to a profound number of other diseases and plays a major part in a multitude of body processes.
Direct lymphedema research has been focused on understanding how lymphedema might effect the overall health of the patient, how the lymph systems "grows," experimental procedures designed to alleviate the condition, and finally to new genetic treatments that can restore the lymph system to a healthy state.
There is no single "research center." There are however, a few sites, such as the University of Pittsburgh that stand out. The focus there has been primary lymphedema and the genetics of lymphedema. Their Lymphedema Family Study seeks to identify the genes responsible
Overseas, research is strong in the United Kingdom under the direction of Dr. Peter Mortimer; and in Australia under the direction of Professor Neil Piller. In continental Europe, much research in corrective surgical procedures such as microsurgery has been done by Drs. Corradine Campisi and Francesco Bocardo in Italy and research is conducted in Poland by Dr. Waldemar Olszewski. In Lymphedema is slowly beginning to be studied in China, South Korea, however, not much literature has yet been forthcoming.
Listed below are organizations and centers involved in research and a direct link to our page on current clinical trials.
June 11, 2008
Lymphedema Resarch Centers and organizations
Lymphatic Research Foundation Patient Registry
PRIMARY LYMPHEDEMA RESEARCH UPDATE
LYMPHEDEMA FAMILY STUDY
lymphedema and lymphatic development
Government Grants/Research Funds
Examples of some research topics are listed below to illustrate the objectives of this program announcement. It is not required that all or any of these ideas be included; investigators are encouraged to submit applications that are relevant to the goals of this program announcement. 1. Comparative studies of gene expression in lymphedematous and normal tissues, using techniques such as laser capture microdissection and high density microarrays to identify molecular targets.
2. Studies on the phenotypic and genotypic differences of lymphatic vascular cells, compared to arterial and venous vascular cells
3. Elucidation of the process of lymphangiogenesis, including the growth factors, cytokines, and matrix molecules associated with the formation of functional lymphatic vessels. A potential role of trophism to lymph nodes, and the effect of reimplantation of nodal tissue on lymphedema.
4. Development of a biophysical model(s) for interstitial fluid exchange across the lymphatic wall, and the role of the lymphatic matrix in the development of lymphedema. Characterization of the physical and biological mechanisms in the propulsion of lymph within lymphatic vessels.
5. The creation of animal models to confirm the identification of putative genes contributing to lymphedema, and the development of animal models to assess new and complementary or alternative treatments.
6. The development of methods to image and quantitate lymph flow to provide useful endpoints for clinical evaluations.
7. Approaches to explain the asymmetry between more and less affected limbs in an individual with primary lymphedema, when the genetics and environment appear to be uniform. Also, the developmental or hormonal basis for onset that occurs during puberty.
8. Studies on the developmental biology and developmental genetics of the lymphatic system, i.e., the identification and characterization of genes important in the organization and regulation of the development of the lymphatic system.
9. Studies on diseases of skin and subcutaneous tissue that result from chronic lymphedema.
10. New methods to prevent or treat lymphedema or lessen its impact on patients.
11. Development of biobehavioral markers to measure the relationship between health-related quality of life (HRQOL) and lymphedema, including markers to measure the impact of therapeutic interventions.
12. A national patient registry and tissue bank. To foster data sharing in addition to presentations and publications, investigators should consider how to make experimental results available to other scientists for data mining, and how to make archived data interoperable with commercially available software.
Lymphatic Research Foundation
I also urge our members and visitors to support the efforts of the Lymphatic Research Foundation
Science now knows that the lymphatic system impacts virtually every function of the human body in health and illness. Despite this, the lymphatics have been historically neglected in both medical school curricula and research institutions. Inadequate methods to diagnose lymphatic disorders and minimally effective therapies are available, with little or no attention paid to the needs of those afflicted by these diseases.
LRF has enjoyed continuous growth and impressive accomplishments both in this country and internationally. LRF has significantly promoted the field of lymphatic research that promises breakthroughs in therapeutic treatments and cures not only for lymphatic disease, lymphedema, and related disorders, but for a multitude of other diseases.
As a result of LRF's successful collaborations with researchers and its relationship with the National Institutes of Health, the Foundation is recognized as a key player in promoting lymphatic research. LRF supporters can feel great pride and satisfaction to know that their Foundation is featured in a current NIH publication, "From Public Advocacy to Research Priorities". LRF is creating the infrastructure necessary to attract the pharmaceutical and biotech industries.
The Lymphedema Family Study aims to determine precisely how lymphedema is inherited in families. Our hope is that identification of the genes responsible for primary lymphedema will provide a better understanding of its cause, and aid in the development of new and better methods for diagnosing and treating lymphedema. The Lymphedema Family Study is a linkage study. Linkage studies, also called linkage analysis, involve a comparison of genetic material between family members with and without lymphedema. In large families this allows the identification of markers on a chromosome, that are associated with a gene responsible for lymphedema. These markers indicate the chromosomal location of that gene. Further research then allows the identification of the causative gene. So far, two genes have been identified that cause primary lymphedema: VEGFR3 and FOXC2
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Vascular endothelial growth factor receptor 3 (VEGFR3) was the first lymphedema gene to be identified. VEGFR3, which was formerly known as FLT4, is located on chromosome 8 and is known to be involved in the formation of lymphatic vessels during prenatal development. VEGFR3 causes congenital lymphedema (swelling which is present from birth). To date we have identified lymphedema-causing genetic changes (mutations) in 5 participating families.
Our article entitled "Hereditary Lymphedema: Evidence for Linkage and Genetic Heterogeneity" was published in the December, 1998, issue of the scientific journal, Human Molecular Genetics. Those who wish to view the Human Molecular Genetics abstract may see it online at PubMed. We also wrote a summary for the National Lymphedema Network Newsletter in January, 1999. Another article, entitled "Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema," describes the affect of 4 different mutations in the VEGFR3 gene. It was published in June, 2000 in the scientific journal Nature Genetics. That abstract may also be read online at PubMed. Copies of these articles are available in most medical libraries.
FOXC2 was the second lymphedema gene to be identified. It is responsible for causing the lymphedema-distichiasis syndrome (LD). Individuals with LD have lymphedema of pubertal or adult onset as well as distichiasis, which is the presence of extra eyelashes. These eyelashes may simply appear long and thick, or they may become ingrown or irritate the eye, in which case they are often removed. Less frequently, individuals with LD may be born with a heart defect, cleft palate (opening in the roof of the mouth), or ptosis (droopy eyelids). We have identified changes or mutations in the FOXC2 gene in 16 families participating in the Lymphedema Family Study.
Lymphedema-distichiasis was first localized to chromosome 16 in 1999 by Mangion et al. The abstract, entitled "A gene for lymphedema-distichiasis maps to 16q24.3," is available at PubMed. However, FOXC2 was not identified as the causative gene until 2001 by Fang at al in an article entitled "Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome." This abstract is also available on PubMed. Our paper on FOXC2, entitled "Truncating mutations in FOXC2 cause multiple lymphedema syndromes," was published in Human Molecular Genetics also in the year 2001. The abstract of our publication is available on PubMed as well.
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Not all hereditary lymphedema is caused by VEGFR3 or FOXC2, indicating that there is at least one other gene (probably many more) responsible for hereditary lymphedema. This phenomenon, the existence of more than one gene responsible for the same condition, is called genetic heterogeneity. We are continuing to look for the location of these additional lymphedema genes.
General results regarding the progress of the study will be made available to participants in several ways. Updates will be posted on this website, and articles will be published in the National Lymphedema Network's Newsletter whenever significant new developments have occured. In addition, if you are a participant in this study and a mutation was identified in your family, you will receive a letter with additional information about the discovery, and you will be offered the opportunity to receive your research results if you want them. Your individual research results will only be disclosed to you or if applicable, your legal guardian, unless we are provided with written permission to release those results to another individual.
In most cases specific genetic information is not yet available for individual families or family members. However, as new genes are identified and proven to be responsible for causing lymphedema in specific families, we will continue to contact the participating family members to inform them of this finding and discuss the impact of this information on them and their family. At that time individual genetic information will be offered to those participants who are interested. However, any genetic information provided by this study will be in the form of research results only and should not be used for medical decision-making without confirmation by a laboratory offering clinical or diagnostic testing. Those individuals who receive research results may elect to have confirmatory testing from a certified diagnostic laboratory. This would involve an additional blood sample and possibly the signing of another consent form. We are currently negotiating with a local laboratory to arrange this testing at a reduced rate for study participants.
We would like to remind you that this is a research study, and therefore, we cannot guarantee that any information will be available to individual families or participants. This study does not provide diagnosis or treatment of lymphedema, and is not designed to result in any direct benefit to the participants. However, it is our hope that it will benefit lymphedema patients in the future. In addition, the participation of families and family members is voluntary and confidential. Advances in understanding the underlying cause of lymphedema are critically dependent on the participation of individuals and families in research such as ours, so for those families participating in our study, we would like to thank you once again. Should you have any questions or concerns about this information or the study in general, please don't hesitate to call Kerry Lorenzo at (412) 624-4657 or (800) 263-2152.
Please support the research work being done at the Lymphedema Family Study at the University of Pittsburgh
INTO THE CAUSES OF LYMPHOEDEMA
For the past 10 years our International Consortium has been working to find the underlying cause of the various types of lymphoedema. Progress was initially slow due to a lack of large families and problems confirming the diagnosis in some cases. Over the past 4 years there have been significant advances in our knowledge, with the finding of 2 genes which cause lymphoedema. In addition our group at St. George's and others around the world have found a number of changes (mutations) within these genes which are believed to be responsible for the development of lymphoedema.
The first gene, responsible for congenital lymphoedema, was discovered in 1998 (Ferrell et al 1998). The gene, called vascular endothelial growth factor receptor 3 (VEGFR3), appears to be responsible for correct development of the lymph system in the fetus.
Alison Evans, PhD student, Cardiological Sciences Department, St. George's Hospital, has now found 4 different mutations in this gene in families with congenital onset lymphoedema.
Lymphoedema-distichiasis syndrome, in which patients with pubertal onset lymphoedema have an extra row of eyelashes which rub on the cornea, is now known to be caused by a gene on chromosome 16 (Fang et al 2000). This gene, called FOXC2, is active during development of the fetus controlling the function of other genes. This controlling effect on other genes probably explains the other findings sometimes associated with this condition such as cleft palate, varicose veins and ptosis. Dr. Rachel Bell, Molecular Genetics Department, St. George's Hospital, has now found mutations in more than 30 different families with this rare condition.
We are continuing our search for a gene for pubertal onset lymphoedema (Meige's disease), the most common form of the condition and are hopeful of a breakthrough in the near future.
Once the gene for a condition is found in a family it offers the opportunity for early diagnosis and the prospect of developing new treatments using our new knowledge of the underlying cause. Tentative steps towards the development of gene therapy for lymphoedema have already been taken (Karkkainen et al 2001).
HOW YOU CAN HELP
We are always eager to include more families in our studies. The more families we are able to include the better our chance of locating the responsible genes. Ideally there should be 2 or more living, affected members in the family but in some cases we will include isolated cases for later mutation screening when the genes are described.
If you wish to take part please contact us:
Department of Cardiological Sciences
Phone 020 8725 5248/2591
Fax 020 8725 2653
Dr. Anne H. Child
Dr. Sahar Mansour
Professor Mansoor Sarfarazi (USA)
Professor Steve Jeffery
Dr. Rachel Bell
Professor Peter Mortimer
Professor Kevin Burnand
Mr. Glen Brice
Mr. Richard Collin
Dr. Anthony Stanton
Dr. Russell Mellor
Join us as we work for lymphedema patients everywhere:
Advocates for Lymphedema
Dedicated to be an advocacy group for lymphedema patients. Working towards education, legal reform, changing insurance practices, promoting research, reaching for a cure.
Lymphedema People / Advocates for Lymphedema
For information about Lymphedema
For Information about Lymphedema Complications
For Lymphedema Personal Stories
For information about How to Treat a Lymphedema Wound
For information about Lymphedema Treatment
For information about Exercises for Lymphedema
For information on Infections Associated with Lymphedema
For information on Lymphedema in Children
Lymphedema People - Support Groups
The time has come for families, parents, caregivers to have a support group of their own. Support group for parents, families and caregivers of chilren with lymphedema. Sharing information on coping, diagnosis, treatment and prognosis. Sponsored by Lymphedema People.
No matter how you spell it, this is another very little understood and totally frustrating conditions out there. This will be a support group for those suffering with lipedema/lipodema. A place for information, sharing experiences, exploring treatment options and coping.
Come join, be a part of the family!
MEN WITH LYMPHEDEMA
If you are a
man with lymphedema; a man with a loved one with lymphedema who you are
to help and understand come join us and discover what it is to be the
instead of the sufferer of lymphedema.
Support group for parents, patients, children who suffer from all forms of lymphangiectasia. This condition is caused by dilation of the lymphatics. It can affect the intestinal tract, lungs and other critical body areas.
Disorders Support Group @ Yahoo Groups
While we have a number of support groups for lymphedema... there is nothing out there for other lymphatic disorders. Because we have one of the most comprehensive information sites on all lymphatic disorders, I thought perhaps, it is time that one be offered.
Information and support for rare and unusual disorders affecting the lymph system. Includes lymphangiomas, lymphatic malformations, telangiectasia, hennekam's syndrome, distichiasis, Figueroa
syndrome, ptosis syndrome, plus many more. Extensive database of information available through sister site Lymphedema People.
Lymphedema People New Wiki Pages
Have you seen
our new “Wiki”
yet? Listed below
are just a sample
of the more than 140 pages now listed in our Wiki section. We are also
on hundred more. Come
and take a
not for Lymphedema
People Online Support Groups
Lymphatic Drainage (MLD) and Complex Decongestive Therapy (CDT)
Associated with Lymphedema
How to Treat a
Infections Associated with Lymphe dema
para-aortic lymph node dissection (EPLND)
Needle Biopsy - Fine Needle Aspiration
Lymphedema Gene VEGFC
Lymphedema Gene SOX18
Home page: Lymphedema People
Page Updated: Dec. 17, 2011