Main Menu

Yearly Archives: 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

TRI Offering Research Forums

Research Forum participant Aliza Brown, Ph.D.

Research Forum participant Aliza Brown, Ph.D.

Nov. 30, 2015 | Do you have a research idea and need some assistance moving forward? Have you submitted a grant application that did not get funded? The Translational Research Institute (TRI) may be able to help through its Research Forums. Research Forums are individually tailored help sessions to address your specific needs. They are private meetings between you and a panel of experts that can help you move your research ideas and projects forward.

Over the past year, TRI has hosted 10 Research Forums for researchers from UAMS, Arkansas Children’s Hospital, Central Arkansas Veterans Healthcare System, and the UAMS Northwest Campus. You can request a Research Forum at

Read here about the Research Forum experience of UAMS’ Aliza Brown, Ph.D.

Dec. 8 Seminar: ‘Introduction to Methods of Financing a Startup’

December 8 2015 Dickey and SmithThe next monthly Health Sciences Innovation and Entrepreneurship (HSIE) seminar will be Dec. 8 at 4 p.m., Cancer Institute, 10th floor, Walton Auditorium. The seminar, “Introduction to Methods of Financing a Startup,” will be presented by two Innovate Arkansas advisors: Ted Dickey, a chartered financial analyst and general partner of CDFP Capital’s real estate fund; and Mike Smith Jr., a managing member of Gravity Arkansas, a member-managed angel fund.
Sponsored by the UAMS Translational Research Institute and UAMS BioVentures, the seminar series is open to all. It is available via WebEx. Get details.

Join WebEx meeting

Meeting number:  808 443 283

Join by phone: +1-855-749-4750 U.S. Toll Free

+1-415-655-0001 U.S. Toll

Access code: 808 443 283

Global call-in numbers  |  Toll-free calling restrictions

Add this meeting to your calendar.

Can’t join the meeting? Contact support.

TRI Research Grants Support UAMS Collaboration in Other States

Nov. 24, 2015 | The UAMS Translational Research Institute announced recipients of two pilot grants aimed at stimulating collaborative research with institutions in other states.

UAMS’ Joshua Kennedy, M.D., is the co-leader of a one-year project with the University of New Mexico Health Sciences Center (UNM HSC).  Another project is co-led by UAMS’ Sean Adams, Ph.D., with John Thyfault, Ph.D., at the University of Kansas Medical Center (KUMC).

The competitive awards were made available through the Western States Consortium Pilot Awards program. The consortium includes the University of Utah in addition to UAMS, KUMC and UNM HSC. Of the eight applications submitted, three one-year pilots of up to $50,000 were awarded, with costs shared by the institutions.

“Collaboration is essential in successful translational research, and I am proud that UAMS researchers represent two of the three projects selected for the 2015 program,” said TRI Director Laura James, M.D.

The UAMS – UNM HSC project, “Host-Pathogen Genomic Determinants of Pediatric Respiratory Infection Severity,” will study the role of genetics in children with acute respiratory infections.

Kennedy is 2013 recipient of the Translational Research Institute’s KL2 Mentored Research Career Development Award. His primary collaborator at UNM, Darrell Dinwiddie, Ph.D., is also a KL2 recipient.

Sean Adams, Ph.D.

Sean Adams, Ph.D.

The pilot award is expected to strengthen their ongoing KL2 research programs by uniquely blending their expertise in genetics, next-generation sequencing, virology, clinical infectious disease, and allergy and immunology.  The project, which will enroll 100 pediatric patients, involves two distinct populations with differing respiratory infection patterns.

The UAMS – KUMC project is titled “Metabolomics Signatures That Occur in Alzheimer’s Disease (AD) Patients With and Without Type 2 Diabetes in Comparison to Controls (non-AD) With or Without Type 2 Diabetes.”  The two institutions are combining their expertise in Alzheimer’s disease and type 2 diabetes (KUMC), and metabolomics and bioinformatics in metabolic disease states including type 2 diabetes (UAMS). They anticipate their work will provide key information on the links between type 2 diabetes and Alzheimer’s. It will also provide metabolic-based information on the cause and development of Alzheimer’s and possibly highlight therapeutic targets.

Other researchers on the project are UAMS’ Kartik Shankar, Ph.D., and KUMC’s Jill Morris, Ph.D., and Brian Piccolo, Ph.D.


UAMS TRI, Community Groups Celebrate Research Partnerships

Nov. 20, 2015 | Twenty-five community groups were honored Nov. 13 for their contributions to research at the 3rd annual Community Partner Celebration sponsored by the UAMS Translational Research Institute (TRI).

TRI Community Advisory Board members Naomi Cottoms, Charles Moore and Ann Huff with Kathryn Hall-Trujillo (center).

TRI Community Advisory Board members Naomi Cottoms, Charles Moore and Anna Huff Davis with Kathryn Hall-Trujillo (center).

The celebration, at the Center at University Park in Little Rock, included welcome remarks from TRI Director Laura James, M.D., and UAMS Chancellor Dan Rahn, M.D. The keynote speaker was Kathryn Hall-Trujillo, M.P.H., founder of the Birthing Project USA, which began as a community project to assist pregnant women and has been replicated in other countries.

The key message to the 88 attendees representing 21 grassroots community organizations and four advisory boards, was how important their work is to finding solutions to society’s most challenging health problems.

Rahn noted that Arkansas ranks at or near the bottom on virtually every key measure of health. No matter how much knowledge there is about obesity, diabetes or cancer deaths, he said, it is of no value without new, innovative approaches to improving health.

“If we keep doing what we’ve been doing we’ll get what we already got,” Rahn said. “We don’t know what to do about the different health outcomes, the health disparities that disproportionately impact on people of color, people in rural areas, people in poverty, and people with low educational attainment.

UAMS Chancellor Dan Rahn, M.D., welcomed UAMS' partners to the celebration in their honor.

UAMS Chancellor Dan Rahn, M.D., welcomed UAMS’ partners to the celebration in their honor.

“The future hinges on some new ways of thinking and developing new knowledge and new methodologies to actually change the future,” he added. “That’s what you can help us with. We thank you for doing this, we thank you for partnering with us. We truly need our partners to help us chart a course for a healthier tomorrow.”

James said the perspective of UAMS’ grassroots partners is key.

“We need to interact with our community partners, and we need to partner with you to do research that is the most meaningful to Arkansans,” James said. “What’s important about tonight is we are celebrating and thinking about how we can in partnership take scientific discoveries or new findings and push them into the homes and families and communities and churches out in the state to improve the health of our state.”

Featured speaker Hall-Trujillo, an Arkansas native whose Birthing Project has become an international model for helping pregnant women, praised the work of the attendees.  A key to the success of her project was realizing the need for communities to understand how important systems and resources work, such as university, medical, education, housing and legal systems.

“The resources we brought to the table were partnered with people who had resources,” Hall-Trujillo said. “What we need to do is be the best relationship builders, the best ambassadors and best liaisons for the families we support.  I can see by looking at this room, that that is exactly what you’re doing, and I applaud you for doing it, and I can see a better place.”

Laura James, M.D., TRI Director, applauded the work of UAMS' community partners.

Laura James, M.D., TRI Director, applauded the work of UAMS’ community partners.

The community organizations honored this year are:

Arkansas Community Health Worker Association (ARCHWA)

Arkansas Voices for the Children Left Behind

Cisneros Center for New Americans

Divine Deliverance

East Arkansas Family Health Center

El Zócalo Immigrant Resource Center

First Baptist Dew Drop Church

Representatives of King's Chapel with their award.

Representatives of King’s Chapel with their award.

Hispanic Women’s Organization of Arkansas

House of Benjamin

Human Rights Campaign

King’s Chapel

Lee County Cooperative Clinic

New Light MBC

Oak Forest United Methodist Church

Planting A Seed Foundation

Pleasant View Ministries Church

Representatives of Oak Forest United Methodist Church with their award.

Representatives of Oak Forest United Methodist Church with their award.

Regenerated Missionary Baptist Church

Rural Community Alliance

Seeds of Liberation

Washington Regional Medical Center Employee Education Department

Young Adult Opportunity Center

The community advisory boards honored this year are:

Arkansas Fetal Alcohol Spectrum Disorders Task Force

Thomas & Lyon Longevity Clinic Patient

and Family Advisory Council

TransForm Health Arkansas Research Working Group

UAMS Hospital Patient and Family Advisory Council




TRIbune Newsletter

The November issue of TRI’s newsletter, The TRIbune, is now available. This issue features our clinical trials services, our promotion of health sciences innovation and entrepreneurship, KL2 Awardee Ling Gao, M.D., Ph.D., published in the NEJM, and TRI-cited publications.  



Request a Mock Study Section by Dec. 4 for February Proposals

TRI is pleased to be able to offer Mock Study Sections for any researcher seeking review of an external grant application. Reviews are available for laboratory, animal and human

TRI Mock Study Section

TRI Mock Study Section

participant study proposals. New submissions and resubmissions will be considered. Interested researchers can request a Mock Study Section through the TRI Portal ( and should submit draft copies of their proposal, budget, and biosketch, as well as comments from a previous submission (if applicable).  The request deadline for review of February proposals is Dec. 4, 2015.

Mock Study Sections are intended to be learning experiences and investigators should plan to be present. Collaborators are also encouraged to attend. Participating investigators will be expected to provide TRI with follow-up information on grant submission outcomes, scores and funding awards.

UAMS Clinical Trials Medicare Coverage Analyses

Dec. 3, 2015 | The Medicare National Coverage Determination (NCD) for Clinical Trials outlines items and services that are not billable to Medicare. These include “items and services customarily provided by the research sponsors free-of-charge for any enrollee in the trial.”  The NCD provides no further clarification for this language.

Historically UAMS has not negotiated when a sponsor offered to pay for an item or service; as a result that offer was accepted as a term of the final agreement. An item or service that is paid by the sponsor is not billable to Medicare and must be designated “research,” even if it would otherwise be considered conventional care.

Based upon a recent review of our process with the Office of Institutional Compliance, UAMS has determined that the sponsor’s offer to pay for such items and services is merely a part of the overall negotiation of the final clinical trial agreement. A number of statements, FAQs, and other language from CMS was analyzed as a part of this review, including the following from a proposed replacement Clinical Trial NCD:  “Medicare does not cover usual patient care when such care is provided free to the Medicare beneficiary or when the study sponsor agreement with investigator sites or the informed consent documents provided to the patient specify that the care will be provided free to participants (§1862(a)(2); 42 CFR 411.4).”

Accordingly, investigators will be able to use the sponsor exhibit as a guide in negotiations rather than something that must be accepted exactly as written. However, once negotiations are complete and the contract is signed, the final signed contract must be followed exactly as written. Once signed, these items will be analyzed as they have been, according to language in the contract, protocol and consent.

The TRI Research Finance Team will now perform coverage analyses in which they initially do their analyses based on the protocol, consent, sponsor exhibit and CTA. However, the team will also provide notes regarding any item or service subject to a proposed sponsor payment that may be billable to Medicare or other payors as conventional care. The research team will have this information available for their negotiations with the sponsor. The final coverage determination for items and services will occur upon completion of the signed clinical trial agreement.


One issue has arisen under this new approach. Billing rules may limit a sponsor’s ability to pay for various activities that occur during certain visits or procedures. For example, where a visit/procedure is bundled, that is, where the services may not be itemized individually for payment, neither the sponsor nor UAMS may pick and choose which items can be invoiced to the sponsor and which can be billed as routine care. The TRI Research Finance Team will identify these instances for investigators as part of the coverage analysis.

For any questions related to this new approach please contact Kennetha Newman, TRI program coordinator, at 501-526-7665.