Amgen Tests IL-Blocker To Treat Symptoms of Hidden Gluten Consumption in Celiac Disease

MedicalResearch.com Interview with:

Markku Mäki, MD, PhD Professor (emeritus) at the University of Tampere and Presently research director at the Tampere University Hospital Tampere, Finland

Prof. Mäki

Markku Mäki, MD, PhD
Professor (emeritus) at the University of Tampere and
Presently research director at the
Tampere University Hospital
Tampere, Finland

MedicalResearch.com: What is the background for this study?

Response: The only treatment for this life-long gluten-induced autoimmune systemic disease is a strict avoidance of wheat, rye and barley, the food cereals which contain gluten, the environmental trigger and driving force in celiac disease.  Gluten causes intestinal
inflammation, usually with (but sometimes without) gastrointestinal or
nutritional symptoms or signs, and with frequent extra-intestinal
diseases. However, it is impossible for celiac disease patients to
avoid gluten entirely and indefinitely and a third of patients report
symptoms on a strict gluten-free diet. Gut mucosal healing is not
optimal in half of the patients, and inflammation and injury is
detected for years after starting the diet, presumably due to
contamination with gluten in the diet. This is why patients are
requesting, and academia and industry are looking for novel adjunct
therapies for celiac disease. Initially, these therapies are tested to
prevent the consequences of hidden gluten; the ultimate goal being
that also celiacs could one day eat safely wheat, barley and rye
products. Some 20 novel experimental therapies are at present actively
being investigated (modifying wheat or different drugs, devices and
vaccines/immunotherapy).

The present study investigated whether blocking interleukin 15, an
important mediator of celiac disease, reduces or prevents
gluten-driven ill health, both the inflammation and injury at the
small intestinal mucosal level and gluten-induced symptoms. The
experimental drug used was Amgen’s AMG 714, a human monoclonal
antibody, used at a low and high dose, in the presence or absence of a
high-dose gluten challenge. Continue reading

DARZALEX® (daratumumab) Approved for Newly Diagnosed Patients with Multiple Myeloma who are Transplant Ineligible

MedicalResearch.com Interview with:

Andrzej Jakubowiak, MD, PhD Professor of Medicine Director, Myeloma Program University of Chicago

Dr. Jakubowiak


Andrzej Jakubowiak, MD, PhD
Professor of Medicine
Director, Myeloma Program
University of Chicago

MedicalResearch.com: What is the background for this announcement? Would you briefly explain what is meant by multiple myeloma?

 

Response: DARZALEX (daratumumab) in combination with VELCADE (bortezomib), melphalan and prednisone – VMP – received U.S. FDA approval for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). With this most recent approval, DARZALEX is now the first monoclonal antibody approved for newly diagnosed patients with this disease.

Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow. Despite the introduction of new medicines over the last decade, which has led to significant improvements in outcomes for patients with multiple myeloma, multiple myeloma remains an incurable disease. In 2018, it is estimated that 30,700 people will be diagnosed and 12,770 will die from the disease in the United States.

Continue reading

Genetic Variants Alter Monoclonal Antibody Effects

Jun-ichi Nishimura, M.D., Ph.D. Assistant Professor Department of Hematology and Oncology Osaka University Graduate School of Medicine C9, 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanMedicalResearch.com Interview with:
Jun-ichi Nishimura, M.D., Ph.D.
Assistant Professor Department of Hematology and Oncology
Osaka University Graduate School of Medicine
C9, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan

MedicalResearch.com: What are the main findings of the study?

Dr. Nishimura: Our major findings are a C5 mutation (c.2654G→A) in Japanese patients with PNH prevents binding and blockade by eculizumab, a humanized monoclonal antibody that targets complement protein C5 and inhibits terminal complement–mediated hemolysis associated with PNH, while retaining the functional capacity of the mutant C5 to cause hemolysis.

MedicalResearch.com: Were any of the findings unexpected?

Dr. Nishimura: Yes, one patient with a poor response to eculizumab was referred to us from Argentina. Although the known C5 polymorphism (c.2654G→A) was not identified in this patient, a new mutation (c.2653C→T) was detected in the base next to the known polymorphism, suggesting the importance of this site in C5 recognition by eculizumab.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Nishimura: Today’s take home messages are that the polymorphism in the target protein might be important to consider in patients with a poor response to the antibody-based treatments for various diseases.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Nishimura:  We will need to verify the distribution of these variants, especially among Asian, South American, Middle Eastern, and African countries.

Citation:

Genetic Variants in C5 and Poor Response to Eculizumab

Jun-ichi Nishimura, M.D., Ph.D., Masaki Yamamoto, M.D., Shin Hayashi, M.D., Ph.D., Kazuma Ohyashiki, M.D., Ph.D., Kiyoshi Ando, M.D., Ph.D., Andres L. Brodsky, M.D., Ph.D., Hideyoshi Noji, M.D., Kunio Kitamura, M.D., Ph.D., Tetsuya Eto, M.D., Toru Takahashi, M.D., Masayoshi Masuko, M.D., Ph.D., Takuro Matsumoto, M.D., Yuji Wano, M.D., Tsutomu Shichishima, M.D., Ph.D., Hirohiko Shibayama, M.D., Ph.D., Masakazu Hase, Ph.D., Lan Li, M.D., Krista Johnson, M.Sc., Alberto Lazarowski, Ph.D., Paul Tamburini, Ph.D., Johji Inazawa, M.D., Ph.D., Taroh Kinoshita, Ph.D., and Yuzuru Kanakura, M.D., Ph.D.

N Engl J Med 2014; 370:632-639
February 13, 2014DOI: 10.1056/NEJMoa1311084