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Sickle Cell Disease: UPMC, Bayer and a Future Cure

by Julia Lee

As the chairman of the University of Pittsburgh’s Department of Medicine, as well as a lung and critical care specialist, Dr. Mark Gladwin oversees research in both lung and heart diseases. Serving as the director of Pitt’s Vascular Medicine Institute, Gladwin is collaborating with Bayer Pharmaceuticals to engineer an upcoming study on sickle cell disease (SCD).

Federally classified as a rare disease, this genetic condition acquired at conception affects around 100,000 people in the United States. Characteristically, SCD is associated with episodes of pain lasting hours or days, sometimes leading to hospitalization. SCD’s physical symptoms are largely due to poor blood circulation that inhibits oxygen delivery to tissues, especially in bone marrow. Currently, SCD has only one FDA-approved treatment: hydroxyurea, which is orally administered daily to help make the condition about 50 percent milder. Patients with severe cases undergo monthly blood transfusions, while in rare incidents, people seek bone marrow transplants. Still, left without a cure, patients are in need of more effective medicines.

One of the world’s largest health care companies specializing in drug development, Bayer Pharmaceuticals, is also interested in developing therapies for lung and heart diseases, as well as blood diseases. Over the last three years, Gladwin has been working on developing this collaboration with Bayer’s Department of Lung and Cardiovascular Drugs to expand opportunities for faculty research partnerships. With its highly-ranked cardiology and pulmonary divisions, UPMC offers countless opportunities for Bayer to partner with specialists interested in almost every aspect of heart and lung disease.

Spearheading the Bayer-UPMC partnerships, Gladwin, along with Dr. Gregory Kato, will co-lead a drug trial on riociguat, a newly-approved treatment for pulmonary hypertension, or high blood pressure in lungs. Based on Gladwin’s pioneering research and discovery that SCD patients have deficiencies in nitric oxide, Gladwin and Kato predict that riociguat may be an effective treatment for SCD. As found in SCD, nitric oxide deficiencies constrict blood vessels and consequently inhibit blood flow. Naturally, nitric oxide binds to protein receptors to dilate blood vessels and circulate blood, and riociguat imitates nitric oxide’s natural effects by binding to the same proteins and triggering the same circulatory response. Therefore, Gladwin and Kato hypothesize that riociguat has the potential to alleviate high blood pressure in patients with SCD.

In their double-blind placebo-controlled study, in which participants are unaware whether they are assigned riociguat or the placebo, Gladwin and Kato’s team will investigate the efficacy and safety of riociguat in treating SCD. Beginning in December 2016, the study will span across 10 hospitals, with Pitt as the lead site. Initially, researchers will be recruiting and enrolling 100 patients who receive routine medical care from sickle cell clinics, but hope to expand the sample size to 200 patients nationwide if the first two years are successful.

The usual protocol for pharmaceutical drug companies is to create a proposal for a drug trial and idea, then to seek for grant money to hospitals for recruiters and to cover the costs of patient care. Uniquely, however, once Gladwin and Kato had submitted their written proposal, Bayer approved grant money for the researchers to finish designing the study and recruit other hospitals. Even more, statisticians from Pitt’s data center will construct databases for multiple hospitals to feed patient data into a central database, making Pitt the center of the study.

Focusing on a translational approach, UPMC’s Adult Sickle Cell Disease Program encourages collaboration between every level of research from laboratory scientists to clinical researchers and physicians who are taking care of patients. While many universities tend to experience a disconnect between scientific research and patient care, the Vascular Medicine Institute unites clinical researchers carrying out trials and scientists concentrated on researching at the lab bench to develop treatments for patients. Moreover, Gladwin and Kato themselves both have research laboratories in the Vascular Medicine Institute, as well as regularly see patients in the hospital and clinics. By considering everyone from patients to community-based organizations as part of a team, Pitt’s intensively-connected research science and clinical trial program is the university’s unique strength.