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Monthly Archives: December 2015


New Drug Just Part of International Effort to Combat Castleman Disease


Carl Guenther receives new drug therapy at UAMS.

Probably few people would say Carl Guenther’s diagnosis was lucky, although he says so, and he has agreement from the world’s foremost expert on Castleman disease, Frits van Rhee, M.D., Ph.D., at the University of Arkansas for Medical Sciences (UAMS).

Guenther, a Wilmington, Ohio, father of two, was diagnosed with Castleman disease and given two years to live just months after his wife died of ovarian cancer. The lucky part? His doctor, who had recently completed medical training, remembered the disease from textbooks and correctly diagnosed it – no easy feat for a rare disease with no formal diagnostic criteria, van Rhee said.

“The average oncology doctor may see one Castleman disease patient in their lifetime, so you cannot possibly expect them to be an expert on a really rare disease,” van Rhee said. “In my opinion, people will die of this disease because they will not get the correct diagnosis, the diagnosis will be delayed, or they will receive inappropriate treatment.”

Patients with Castleman disease overproduce lymphocytes, leading to enlarged lymph nodes, and they have night sweats and fever. They may also have liver failure, renal failure, accumulation of fluid in the chest and abdomen, respiratory failure and death. The tumors that can result from the disease are usually benign, but Castleman can progress to malignant lymphoma.

“Although it’s a lymph node disorder, sometimes lymph nodes can look like Castleman disease due to other disorders, particularly diseases like lupus and autoimmune disorders,” van Rhee said. “So just looking at the microscope and saying ‘This looks like Castleman disease’ is not sufficient.”

Having the right diagnosis helped Guenther find van Rhee, who 10 years ago enrolled him in the life-saving international study of the drug siltuximab, the first-ever drug for Castleman disease approved in 2014 by the Food and Drug Administration and the European Medicines Agency.

“I lucked out,” Guenther said.

Siltuximab is a major advance in the treatment of multicentric Castleman disease, an aggressive form of the disease that kills about 38 percent of patients within five years. With the new drug, the percentage of survivors should increase based on clinical trial results showing siltuximab successfully treated 34 percent of patients with multicentric Castleman disease.

Still, with the disease affecting an estimated 4,000 to 6,000 people in the U.S. alone, that leaves many without effective treatment. The drug is also not a cure, so patients like Guenther will have to take siltuximab the rest of their lives to avoid relapse.

Second Act
It took international collaboration among physician researchers and their patients to get siltuximab to market. That same kind of collaboration is being used in hopes of continued groundbreaking discoveries and other advances such as standard diagnostic criteria, van Rhee said.

Van Rhee is a founding member of the Castleman Disease Collaborative Network (CDCN), a worldwide community of physicians, researchers, patients and supporters working to combat the disease. Research and patient support are core missions for the CDCN, linking people through its website, The website’s components include patient information, such as where to find medical treatment, and the latest information about the disease. The group is also developing diagnostic criteria for physicians to help remove the element of luck.

“You have a disease that is fairly complex and it’s very rare, so that’s a set up for failure to some extent isn’t it?” van Rhee said. “That’s why it’s important to get some solid information out there. “

The CDCN is developing a patient registry and biorepository of tissue and blood samples to aid with its research component. Much of the organization of the collaborative and its website development has been led by one of van Rhee’s patients, David Fajgenbaum, M.D., M.B.A. His inspiring success story while battling Castleman disease was recently featured in the Philly Voice.

A major barrier to finding and tracking Castleman disease patients is the lack of ICD 9 codes for the disease. Used primarily for billing purposes, such international codes are entered into medical records and stored in databases, giving researchers the ability to query them and to track how many people have certain diseases. The CDCN is pursuing ICD 9 codes for three major forms of Castleman disease: Multicentric Castleman disease; idiopathic (unknown cause) multicentric Castleman disease, and Unicentric Castleman disease, a form in which lymph nodes are enlarged in one area and can usually be cured with surgery.

The CDCN also raises money for research. One of its funded studies is being led by van Rhee, who hopes to identify a specific “fingerprint” for Castleman disease by analyzing the blood proteins of patients.

“Although Castleman disease is suggested to always be driven by Interleukin 6 (a protein involved in inflammation and infection responses), there are some patients who get sick without developing high Interleukin 6 levels,” van Rhee said. “So we want to have a better understanding of the biology of the patients.”

TRI Announces 2015 KL2 Award Recipients!

Marquis and Raye-Griffith (4)PS sizedUAMS’ Bryce Marquis, Ph.D., an assistant professor of geriatrics, and Shona Ray-Griffith, M.D., an assistant professor of psychiatry, were recently named recipients of the Translational Research Institute’s 2015 KL2 Mentored Research Career Development Awards. 

Marquis’ KL2 project is testing nutritional therapies to improve respiratory efficiency for heart failure patients. He anticipates the results of his work will direct the development of a new nutritional approach that can be used alone or with exercise to improve health outcomes in heart failure patients.

Ray-Griffith’s KL2 project is the first study using repetitive transcranial magnetic stimulation (rTMS) to treat neuropathic pain in pregnant women. rTMS uses a magnetic force to change the way nerves work in the brain. Because it is non-invasive and localized, rTMS is attractive for use in special populations, such as pregnancy, said Ray-Griffith, who has a secondary appointment in the Department of Obstetrics & Gynecology.

For the next two years, the KL2 awards will provide Marquis and Ray-Griffith with 75 percent of their salaries (up to $95,000), and up to $25,000 for research, tuition, travel expenses and education materials in support of their career development plans.

Marquis’ mentors are Robert Wolfe, Ph.D., Gohar Azhar, M.D., and Jeanne Wei, M.D., Ph.D., all in the Department of Geriatrics;  Elisabet Borsheim, Ph.D., in the Department of Pediatrics; and Gunnar Boysen, Ph.D., in the College of Public Health. Marquis joined the UAMS College of Medicine faculty this year from the University of Central Arkansas, where he was an assistant professor of chemistry. He received his doctorate in analytical chemistry at the University of Minnesota, Minneapolis. He was also a National Research Council postdoctoral associate at the National Institute of Standards and Technology, Gaithersburg, Md.

Ray-Griffith’s mentors are Pedro Delgado, M.D., and Zachary Stowe, M.D., both in the Department of Psychiatry; and Everett Magann, M.D., in the Department of Obstetrics & Gynecology. She joined the UAMS College of Medicine faculty in 2013 with clinical appointments in the Women’s Mental Health program and as a psychiatry consult and liaison. She received her academic appointments in 2014 in the departments of Psychiatry and Obstetrics & Gynecology. She was a research fellow in the Women’s Mental Health Program and also served her residency and internship with the Department of Psychiatry. Ray-Griffith received her medical degree from the University of Texas Medical Branch in Galveston, and she is certified by the American Board of Psychiatry and Neurology.

NCATS Seeks Applications to Repurpose Existing Drugs

The National Center for Advancing Translational Sciences (NCATS) is seeking applications for rigorous, pre-clinical research projects that are based on repurposing existing drugs or biologics. Through this new funding opportunity, NCATS anticipates committing $4.3 million in fiscal year 2016 to issue 10 to 15 awards in support of studies that establish the rationale for a clinical trial.

Pre-clinical studies funded through this initiative will serve as “use cases” to demonstrate the utility of an independent crowdsourcing effort or of a computational algorithm to predict new therapeutic uses of an existing drug or biologic. The goal of an individual project must be to explore the potential new use of an existing investigational therapeutic or one already approved by the Food and Drug Administration to treat another disease.

Interested researchers should submit a letter of intent by Dec. 13, 2015. Applications are due Jan. 13, 2016.

To learn more about RFA-TR-16-001, contact