lymphfantastic

Die Suche geht weiter- The search goes on

Collaboration between two Stanford labs has resulted in the discovery of a molecular cause for lymphedema the first possible drug treatment for it

4 Kommentare

Study finds first possible drug treatment for lymphedema

Collaboration between two Stanford labs has resulted in the discovery of a molecular cause for lymphedema and the first possible drug treatment for it.

Woman standing in front of her garden and home

Tracey Campbell suffers from lymphedema and is participating in a clinical trial of a drug to determine whether it can treat the painful condition.
Mark Williams

Tracey Campbell has lived for seven years with lymphedema, a chronic condition that causes unsightly swelling in her left leg.

The disease, which stems from a damaged lymphatic system, can lead to infections, disfigurement, debilitating pain and disability. There is no cure. The only available treatment is to wear compression garments or use massage to suppress the swelling, which can occur throughout the body in some cases. Campbell — who had two quarts of excess water in her left leg by the time she was diagnosed — has for years worn restrictive garments 24 hours a day and has spent an hour each night massaging the lymph fluid out of her leg.

Lymphedema is uncomfortable, exhausting and dangerous if left uncontrolled. As many as 10 million Americans and hundreds of millions of people worldwide suffer from the condition, many from the after-effects of cancer therapy treatments.

“There’s this extra layer of emotional burden,” said Campbell, who added that she has to be constantly vigilant to protect against infection. “All you want to be is normal.”

Now there’s new hope for a possible pharmaceutical treatment for patients like Campbell. A study led by scientists at the Stanford University School of Medicine has uncovered for the first time the molecular mechanism responsible for triggering lymphedema, as well as a drug with the potential for inhibiting that process.

The study was published May 10 in Science Translational Medicine.

“We figured out that the biology behind what has been historically deemed the irreversible process of lymphedema is, in fact, reversible if you can turn the molecular machinery around,” said Stanley Rockson, MD, professor of cardiovascular medicine and the Allan and Tina Neill Professor of Lymphatic Research and Medicine at Stanford. Rockson shares senior authorship of the study with Mark Nicolls, MD, professor of pulmonary and critical care medicine. Stanford research scientists Wen “Amy” Tian, PhD, and Xinguo Jiang, MD, PhD, share lead authorship of the study and are also affiliated with the Veterans Affairs Palo Alto Health Care System.

‘Fundamental new discovery’

“This is a fundamental new discovery,” said Nicolls, who is also a researcher at the VA Palo Alto.

Stanley Rockson

Stanley Rockson

The researchers found that the buildup of lymph fluid is actually an inflammatory response within the tissue of the skin, not merely a “plumbing” problem within the lymphatic system, as previously thought.

Working in the lab, scientists discovered that a naturally occurring inflammatory substance known as leukotriene B4, or LTB4, is elevated in both animal models of lymphedema and in humans with the disease, and that at elevated levels it causes tissue inflammation and impaired lymphatic function.

Further research in mice showed that by using pharmacological agents to target LTB4, scientists were able to induce lymphatic repair and reversal of the disease processes.

“There is currently no drug treatment for lymphedema,” Tian said. Based on results of the study, the drug bestatin, which is not approved for use in the United States but which has been used for decades in Japan to treat cancer, was found to work well as an LTB4 inhibitor, with no side effects, she said.

Based on the research, bestatin (also known as ubenimex), is being tested in a clinical trial that started in May 2016 — known as ULTRA — as a treatment for secondary lymphedema, which occurs because of damage to the lymphatic system from surgery, radiation therapy, trauma or infection. Primary lymphedema, on the other hand, is hereditary. The results of the research pertain to both types.

Rockson is principal investigator for this multisite phase-2 clinical trial.

“The cool thing about this story — which you almost never see — is that a clinical trial testing the therapy has already started before the basic research was even published,” Nicolls said. “This is the first pharmaceutical company-sponsored trial for a medical treatment of lymphedema, a condition that affects millions.”

Nicolls and Tian are co-founders of Eiccose LLC. Eiccose is now part of Eiger BioPharmaceuticals, which gets the drug from Nippon Kayaku in Japan. Eiger is sponsoring the clinical trial. Nicolls and Rockson are both scientific advisers to the company.

Two labs, two diseases

The study, which got underway about four years ago, began somewhat uniquely as a collaboration between two labs that were studying two completely different diseases. At the time, the Nicolls lab, where Tian works, was studying pulmonary hypertension. The Rockson lab was conducting lymphedema research.

Mark Nicolls

Mark Nicolls

The two teams met through SPARK, a Stanford program designed to help scientists translate biomedical research into treatments for patients.

“I was in a privileged position of seeing two faculty conducting important research and recognizing the possible link in causality,” said Kevin Grimes, MD, associate professor of chemical and systems biology and co-founder of SPARK. “It occurred to me that both diseases affected vascular tissues and had strong inflammatory components.”

“He blind-dated us,” Nicolls said. “When Amy Tian and I looked at the data from Stan’s research, Amy said, ‘It looks like it could be the same molecular process.’”

“It was an arranged marriage between us and Stan which worked out great,” Tian said.

At the time, Rockson had begun to suspect that lymphedema was an inflammatory disease. This led to his team’s discovery that the anti-inflammatory drug ketoprofen successfully helped to relieve lymphedema symptoms, although it wasn’t a perfect drug; side effects were a concern, and it remained unclear how the drug worked at the molecular level.

Meanwhile, the Nicolls lab had discovered that LTB4 was part of the cycle of inflammation and injury that keeps pulmonary hypertension progressing. When researchers blocked LTB4 in rats with the disease, their symptoms lessened and blood vessels became less clogged, lowering blood pressure in the lungs.

“When we became aware of Mark’s work, we began to realize that we were both possibly dealing with the activation of steps downstream of the 5-LO [5-lipoxygenase] pathway,” Rockson said. “This became intriguing and formed the basis of our relationship.”

Joining forces

The two teams joined forces to figure out the mechanism that triggered lymphedema, hopefully revealing a target for drug treatment in humans. After determining that ketoprofen was primarily working on the 5-LO pathway, the researchers began blocking the various endpoint pathways after 5-LO activation in mouse models of lymphedema, Rockson said.

“It turned out that, in fact, we were both dealing with the same branch, which is LTB4,” Rockson said.

When all of the sudden one of your limbs begins to swell, you want to understand what the heck is going on.

“So now it became clear we really were dealing with a very similar biological process in two different diseases,” he said. “Because of Mark’s work in pulmonary hypertension, we knew that we had an ideal form of therapy that we could try in lymphedema as well.”

The Nicolls lab had used the drug bestatin, which blocks the enzyme that generates LTB4, to reverse pulmonary hypertension disease processes. When researchers tested bestatin in the mouse lymphedema model, it worked to reverse symptoms of that disease.

“I’m still in awe,” Rockson said. “There are few situations where you take a problem at the bedside, and go into the lab, and then take discoveries back to the bedside. It’s amazingly gratifying.”

Campbell, who is now participating in the double-blinded, placebo-controlled bestatin trial at Stanford, remains hopeful.

“When all of the sudden one of your limbs begins to swell, you want to understand what the heck is going on,” she said. “It’s a tough condition that few people seem to care about, even though millions and millions suffer with it. We’re hoping for something that gives some relief.”

Other Stanford authors are research associate Jeanna Kim; former medical students Adrian Begaye, MD, and Abdullah Feroze, MD; Roham Zamanian, MD, associate professor of medicine and director of the Adult Pulmonary Hypertension Service; Gundeep Dhillon, MD, associate professor of medicine and medical director of the Stanford Lung Transplant Program; and research assistants Eric Shuffle and Allen Tu. Shuffle and Tu are affiliated with both Stanford and the VA Palo Alto.

Researchers at Georgia Institute of Technology, Virginia Commonwealth University, the University of Michigan Health Systems and the University of Illinois at Chicago are also co-authors.

Eiger BioPharmaceuticals has licensed intellectual property developed by Tian, Rockson, Jiang, Kim and Nicolls involving the targeting of LTB4 for the treatment of lymphedema.

Stanford’s Department of Medicine supported the work.



Stanford Medicine integrates research, medical education and health care at its three institutions – Stanford University School of Medicine, Stanford Health Care (formerly Stanford Hospital & Clinics), and Lucile Packard Children’s Hospital Stanford. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu.

 

 

http://med.stanford.edu/news/all-news/2017/05/study-finds-first-possible-drug-treatment-for-lymphedema.html

Advertisements

Autor: monica boersch

Vor ein paar Jahre bin ich an Krebs erkrankt, bedingt durch meine Wertheim OP, Bestrahlung und Afterloading habe ich Lymphödeme bekommen, für mich sehr überraschend da ein paar Jahre dazwischen lagen, ich wusste das etwas nicht stimmt aber leider konnten unzählige Ärzte nicht helfen. Hier ist es auch so, wie in viele viele andere Länder auch, dass Lymphatische Erkrankungen erstens nicht wirklich ernst genommen werden und zweitens das kaum ein Arzt darüber Bescheid weiß, wie den auch, wenn in den Lehrbüchern so gut wie NICHTS steht. Mein Bestreben ist alles zu tun was in meiner Macht steht um dafür zu sorgen das jeder der betroffen ist weiß was er/ sie tun kann um sein Leben wieder so gestalten zu können wie er/sie das möchte. . Ich suche und suche immer weiter nach alternativ Möglichkeiten um meinen Leben so normal wie möglich zu gestalten. Die Empfehlungen die ich gebe sind bei mir durchaus wirksam und ich erziele gute Erfolge und behalte meine Lebensqualität. Mein Blog ist kein Ersatz für eine Ärztliche Betreuung und ich empfehle jeden mit seinem Arzt über Therapie Möglichkeiten etc. zu sprechen. Ich kann nur anregen und durch meine eigene, persönliche Erfahrung eventuell einen weg aufzeigen. Seit 2009 beschäftige ich mich weit über das übliche hinaus mit Lymphödeme. Nicht nur die „Diagnose“ interessiert mich, sondern ebenso was für einen Effekt es hat auf unser Sozialleben und unser Selbstwertgefühl. Ich habe viel Zeit und Geld investiert in andere Länder zu reisen um alternativen kennenzulernen, ich war bei Internationale Firmen als Gast um zu sehen welche Lösungen geboten werden, habe fast jeden Lymphologischen Kongress besucht um mich weiter zu bilden und einige Projekte als Freelancer machen können. Wie ihr sieht ist das weitaus mehr als nur ein Blog, es müssen sich grundliegende Dinge verändern um uns alle das zu geben was wir verdienen, Respekt, Empathie und das Bewusstsein das wir nichts Vorübergehendes haben, sondern das dieses ein Teil unseres Lebens ist und auch bleibt. After being diagnosed with Cancer and going through treatments, Wertheim operation, radiation therapy and afterloading I was suddenly hit by Lymphedema. Totally surprising since nobody even gave me a hint that this could happen. Running from one doctor to the other trying to find out what is wrong with me and why my body was changing so quickly, once again being in the situation of not having control of anything. This made me so angry that I started studying like crazy, I wanted to find out why we are left alone, why doctors don’t have a clue (sorry, most doctors) about Lymphedema and the consequences in all aspects of our lives. Sadly, I had to realize that hardly anyone knows anything about it. I started my quest to find alternatives in treatments, I traveled around the world investing my time and money, fortunate enough to spend time in companies specialized in Lymphedema treatment to learn all that I could and can. I hardly miss any Lymphatic congress, listening to the internationally known doctors, discussing what is important for us as patients. I have done some freelance work for the companies that I believe in and had the chance to work with a wonderful company in New Jersey. I have tested alternatives and I am still searching and studying because it is my quest to change things for all affected by this, not only our physical wellbeing but most importantly the impact that it has on our daily life. It’s not something that’s going to go away, it’s with us until the end and the minimum that we can expect is being taken seriously, respect and empathy for our situation and the importance for all of us that have the possibilities to change things for the better. There is so much work to do, and I am not going to give up. As you can see this is more than a blog. If you find something interesting on Lymphfantastic but you are having problems with the German, then just send me a message and I will be happy to translate that for you, my native language is English so that is no problem. Have a great day and looking forward to hearing from you soon. Bless you all, Monica

4 Kommentare zu “Collaboration between two Stanford labs has resulted in the discovery of a molecular cause for lymphedema the first possible drug treatment for it

  1. I heard Dr. Rockson’s presentation at the recent Klose Lymphedema Conference and came away very encouraged at his work! Fingers crossed!

    Gefällt 1 Person

  2. Hi Monica ich freue mich immer über Nachrichten aus dem LYMPHFANTASTIC aber mit denenglischen Nachrichten kann ich leider nichts anfangen.Schade .Freue mich und hoffe das du bald wieder etwas in meiner Sprache postest.
    Liebe Grüße Marianne

    Gefällt 1 Person

    • Hallo liebe Marianne, ja du hast schon recht. Mein Muttersprache ist ja English und leider werden oft Studien etc. ausschließlich auf English geschrieben. Ich hatte eigentlich ein “ tool“ also Werkzeug extra eingegeben das alles für Leser übersetzt werden kann, sicherlich nicht 100 % richtig aber wenigstens das man es versteht. Vom können her kann ich alles übersetzten und ich verspreche dir das bei wichtigen dingen( und der Artikel war eins davon) wenigstens ein teil zu übersetzen. Mein Blog erreicht ja betroffenen weltweit, wir sind viele, und deshalb flutscht mir das manchmal durch. Ich hoffe du kannst mir verzeihen, ich gelobe Besserung 🙂 Alles liebe für dich und danke das du die zeit nimmst für mich! Pass auf dich auf LG

      Gefällt mir

Kommentar verfassen

Trage deine Daten unten ein oder klicke ein Icon um dich einzuloggen:

WordPress.com-Logo

Du kommentierst mit Deinem WordPress.com-Konto. Abmelden / Ändern )

Twitter-Bild

Du kommentierst mit Deinem Twitter-Konto. Abmelden / Ändern )

Facebook-Foto

Du kommentierst mit Deinem Facebook-Konto. Abmelden / Ändern )

Google+ Foto

Du kommentierst mit Deinem Google+-Konto. Abmelden / Ändern )

Verbinde mit %s