SUNY Buffalo Scientist Recognized As World Leader In Cystic Fibrosis Research

Internationally recognized Cystic Fibrosis expert and State University of New York at Buffalo clinical professor of pediatrics Drucy S. Borowitz, MD has received the 2015 Stockton Kimball Award for outstanding scientific achievement and service

She accepted the honor at a May 28 SUNY Buffalo School of Medicine and Biomedical Sciences Faculty and Staff Recognition Awards celebration, and will deliver the Stockton Kimball Lecture in 2016. The award and lecture memorialize Stockton Kimball, MD, who was dean of the medical school from 1946 to 1958, and contributed to physician training for more than 25 years.

Dr. Borowitz is also currently lead investigator in two second-phase trials, and a major contributor to clinical research on cystic fibrosis, its genetic components, pharmacologic management and the associated field of pediatric nutrition.

During the awards event, Suzanne G. Laychock,
PhD, SUNY Buffalo senior associate dean for faculty affairs and facilities, noted Dr. Borowitz’s “clinical and scholarly passion for the care of patients with cystic fibrosis.”

Through most of her 27-year career at SUNY Buffalo, Dr. Borowitz has also directed the Cystic Fibrosis Center at Women and Children’s Hospital of Buffalo (WCHOB).

A leading researcher of enzyme replacement therapy to correct digestive abnormalities that affect cystic fibrosis patients, Dr. Borowitz has pioneered nutritional research using novel agents and dietary supplements hoped to address the challenges experienced by her CF patients suffering from colonopathy and pulmonary function.

Since 1987, Dr. Borowitz’s research has been continuously funded, and during that time she has authored or coauthored an extensive bibliography of scholarly publications, including 35 articles within the past five years — many of them in high-profile peer-reviewed journals.

Cystic fibrosis is a rare, genetic, life-shortening disease that affects approximately 30,000 Americans, and patients with CF have a shortened lifespan because of the disease. Cystic fibrosis causes breathing and digestive problems, and of individuals with CF, about four percent are believed to have the G551D mutation, in which the cystic fibrosis transmembrane regulator (CFTR) proteins do not work properly. Dr. Borowitz played a key role in developing Vertex Pharmaceuticals‘ breakthrough drug Kalydeco (ivacaftor), which was discovered as part of a collaboration with Cystic Fibrosis Foundation Therapeutics, Inc., the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. Kalydeco was approved in 2012 for treatment of the relatively small number of cystic fibrosis cases overall who have at least one copy of the G551D mutation in the transmembrane conductance regulator (CFTR). The Cystic Fibrosis Therapeutics Development Center was the first site in the world to recruit patients for a Phase 3 clinical trial of Kalydeco.

“We enrolled the first patient in the study, which began in 2009, so there is a patient in Western New York who has been on this drug longer than anyone in the world,” says Dr. Borowitz, who also co-authored the study, “Cystic Fibrosis and the Role of Gastrointestinal Outcome Measures in the New Era of Therapeutic CFTR Modulation“ (J Cyst Fibros. 2015 Mar;14(2):169-77. doi: 10.1016/j.jcf.2015.01.006. Epub 2015 Feb 100) published in the Journal of Cystic Fibrosis, and coauthored by F.A. Bodewes and H.J. Verkade of the Pediatric Gastroenterology and Hepatology department, University of Groningen University Medical Center at Groningen, The Netherlands; J.P. Taminiau of the European Medicines Agency Pediatric Committee, London, U.K.; and M. Wilschanski of the Pediatric Gastroenterology department at Hadassah Hebrew University Medical Center in Jerusalem, Israel.

The coauthors note that with development of new drugs that directly affect CFTR protein function in progress, clinical trials are being designed or initiated for a growing number of patients with cystic fibrosis, but that the currently available and accepted clinical endpoints, FEV1 and BMI, have limitations.

The aim of their report is to focus attention on the need and ample possibilities for development and validation of relevant gastrointestinal clinical endpoints for scientific evaluation of CFTR modulation treatment, particularly in young children and infants. The researchers observe that the gastrointestinal tract offers manifold potential opportunities to measure CFTR protein function and to systematically evaluate CF-related clinical outcomes, based on the principal clinical gastrointestinal manifestations of CF: which include intestinal pH, intestinal transit time, intestinal bile salt malabsorption, intestinal inflammation, exocrine pancreatic function, and intestinal fat malabsorption. In the report, they present a descriptive analysis of various gastrointestinal outcome measures for clinical relevance, reliability, validity, responsiveness to interventions, and feasibility — in particular in young children and the availability of reference values.

Clinical Trials Include National Nutrition Study

Known internationally for her expertise in clinical trial investigation, Dr. Borowitz has led or co-led more than 35 clinical studies over 20 years, and she also led a Journal of Pediatrics study that resulted in new guidelines for managing infants with the disease. On two second-phase trials she currently leads, she is contributing to clinical research on cystic fibrosis, its genetic components, pharmacologic management and pediatric nutrition. Since 2012, she also has led a study to assess the effects of antioxidant-enriched multivitamin supplements on inflammation and oxidative stress in cystic fibrosis patients. The trial is closely aligned with her independent research.

Dr. Borowitz is a co-principal investigator (PI) on the Baby Observational and Nutritional Study (BONUS) a prospective, multi-center, observational cohort study that is following incident cases of CF for up to 12 months in 225 infants at hospitals across the U.S. Observational data will be collected from routine clinical care visits as recommended by the Cystic Fibrosis Foundation (CFF) evidence-Based Guidelines for the Management of infants with Cystic Fibrosis. Subjects may be enrolled up to three and one half (3.5) months of age, and will be seen at months one, two, three, four, five, six, eight, ten and twelve.

The study, which is funded by the National Institute for Diabetes and Digestive and Kidney Diseases, is a spinoff of a privately funded trial Dr. Borowitz has led as national senior PI since 2011. Lung function is very hard to measure in infants, but growth is not, and in this study the investigators aim to define growth in infants with CF in the first year of life with research quality precision and to understand factors that interfere with good growth. Pancreatic enzyme replacement therapy (PERT) will be also be studied in a subgroup of infants. Two different doses of PERT will be evaluated for improving fat and nitrogen absorption in infants with CF, and the period adjusted change in coefficient of fat absorption observed. Treatment will consist of two-14 day consecutive treatment windows with 72 hour stool collections during the last three days of treatment.

This study is currently recruiting participants and is designed to minimize study subject and family stress and inconvenience while ensuring that the study is conducted following international Conference on Harmonisation: Good Clinical Practice (GCP) Consolidated Guidance to ensure subject safety and data integrity. For this reason, the study is structured around the family’s routine clinical care during the first year of life and each visit occurs at the time of an infant’s monthly clinic visits. Total duration of an individual subject’s participation will be up to 12 months. Subjects will be seen for a total of up to nine visits, and total duration of the study is expected to be 24 months (12 month recruitment period and 12 month follow up period). For more information, visit: https://clinicaltrials.gov/ct2/show/study/NCT01424696#contacts

Primary outcome measures of the Baby Observational Nutrition Study include: incremental gain in weight, length, and head circumference over a time frame of one year, to define and describe incremental weight gain and linear growth in the first year of life utilizing research quality growth measures that will be applicable as efficacy outcomes for future interventional studies in infants with CF.

Dr. Borowitz frequently gives invited presentations for national and international audiences, and is involved in efforts to bring more gastroenterologists into the cystic fibrosis field — for instance contributing her expertise and leadership to NIH study sections and committees, scholarly journals and the Cystic Fibrosis Foundation.

Among her many service activities at UB, she directs the medical school’s Integrating Special Populations team, and serves on the Clinical Research Office Advisory Committee.

In 2014, the Cystic Fibrosis Foundation gave Dr. Borowitz one of its highest honors, the Richard C. Talamo Distinguished Clinical Achievement Award. Later that same year, the University recognized Exceptional Scholar Sustained Achievement Award She has also received the Children’s Champion Award for her notable patient- and family-centered care from the WCHOB’s Family Advisory Council, and been honored by UB medical students with a Louis A. and Ruth Siegel Award honorable mention for teaching excellence in teaching and mentoring medical students, residents and fellows.

Sources:
State University of New York at Buffalo
Journal of Cystic Fibrosis
Clinicaltrials.gov
Vertex Pharmaceuticals
UT Southwestern Medical Center,

Image Credits:
State University of New York at Buffalo