Finding a Treasure in Milwaukee
By: Linda Bevec–ARPKD/CHF Mom
Most rare things are a treasure of great worth sought after by many. Rare coins, vintage jewelry, an original John Lennon album. But not so with rare diseases – they rarely occur, are usually very complicated, and no one would ever want one, let alone seek one out. There is usually very little information about a rare disease, few physicians who are dedicated to them, and far fewer pharmaceutical companies willing to put their time and money into research and development. As the mother of a child with a rare disease I consider myself both unfortunate and lucky at the same time. Unfortunate that my daughter was born with a “rare” disease that comes packed with a host of serious, complex life-long medical complications and a fair amount of mom-anxiety. And yet I feel very lucky to live so close to one of the top medical doctors and researchers in the world for her disease.
After years of practice as a leading Pediatric Nephrologist, Dr. Ellis D. Avner became intrigued by Polycystic Kidney Disease, and especially the rare recessive form affecting children with a wide spectrum of chronic and progressive kidney and liver manifestations. His concern to help sick children eventually led to more questions about the disease than answers, and when he couldn’t answer all of the questions from parents in desperate search them, Dr. Avner turned to the laboratory and medical research to dig deeper. In 2006, he came to Milwaukee to direct the NIH-supported Clinical and Translational Research Program in Polycystic Kidney Disease.
I had the opportunity to talk with Dr. Ellis D. Avner and Dr. William Sweeny at Children’s Hospital of Wisconsin to learn more about their work in the Polycystic Kidney Disease Clinic, a comprehensive center that provides patients with one-stop access to specialists who cover the broad array of medical issues and concerns with ARPKD/CHF, while also keenly focused on medical research. Dr. Avner also leads the nephrology research at the Children’s Hospital Research Institute and remains involved in both the clinical care of children with ARPKD/CHF and the development of new therapies and treatments; a win-win combination. Dr. Avner is no doubt one of the world’s leading experts in ARPKD/CHF and has devoted more than 30 years of his career to this disease. When he came to Milwaukee to direct this initiative, he envisioned a center tied to the day-to-day clinical care of children with ARPKD/CHF, while also focused on research and translational medicine; a center of excellence to better understand and advance pediatric medicine for this disease both now and in the future.
My 12- year old daughter Claire received a kidney transplant from Children’s Hospital of Wisconsin nearly three years ago and is closely monitored by Dr. Avner and an entire team of kidney/liver specialists. I’ve known Dr. Avner since Claire was a newborn during the first weeks and months of her fragile life in 2001. Like so many of you, the devastating news of her diagnosis and thoughts of losing her sent me on a mom-mission for answers, specialists, treatments, cures and anything remotely possible for sustaining her life. After scouring the Internet, I found Dr. Avner who at the time was in Cleveland. We later talked on the phone and then met at a medical conference. His compassionate heart and keen motivation to understand this disease was an anchor of hope for me back then, as it is now.
So, what has Dr. Avner working on now? “Our goal is simple” he said. “It starts with patients and ends with patients.” Sounds simple enough, but between that starting and ending point is where ALL our children are…babies diagnosed in utero with this disease, newborns struggling to survive, toddlers learning to walk with enormous kidneys, school age children managing the day-to-day challenges of having blood drawn, controlling blood pressure, fighting infections, taking medications, and preparing for kidney and/or combined kidney/liver transplants.
Dr. Avner directs the NIH-supported Clinical and Translational Research Program in Childhood Polycystic Kidney Diseases (PKD) at Children’s Hospital of Wisconsin. His 30 plus year basic research program has largely focused on the molecular and cellular pathophysiology of PKD, with a long-term goal of developing specific therapies to target the unique cellular and vascular phenotype of these disorders. PKD, which comprises genetically dominant and recessive congenital diseases, causes significant morbidity and mortality, affects over 13 million individuals worldwide, and currently has no disease-specific therapy. “Our laboratory has delineated the unique phenotype of cystic epithelium and endothelium,” reports Dr. Avner. PKD results from mutations in 3 specific cystic genes, leading to the formation of aberrant multimeric cystoprotein complexes which bind to a number of key cellular signaling pathways at multiple intracellular/extracellular locations. Such “cystoprotein complexes” result in qualitative/quantitative abnormalities in the EGF-R axis, altered G-protein/ cAMP/intracellular calcium expression, and abnormal cell-matrix interactions. Abnormal signal integration from such complexes leads to renal cell proliferation, reversal of absorption to secretion in organ-specific tubular structures, and abnormal neovascularization. These abnormalities consequently lead to cyst formation, progressive enlargement and fibrosis with renal and hepatobiliary failure and vascular disease. Targeting specific abnormal PKD signaling is the focus of current pharmacological approaches in animal models and early clinical trials. New translational approaches are emerging, with the most promising currently focused on inhibition of abnormal signaling of: 1) the EGF-R/ c-src axis; 2) the G-protein/cAMP/intracellular calcium axis; and 3) neovascularization of enlarging cystic structures and abnormalities in cystic vasculature.”
The Children’s Research Institute in Milwaukee advances state-of-the-art pediatric health care through translational research programs. They work to find life-saving treatments in diseases that affect children as well as interventions that enhance quality of life for children and families living with chronic health conditions. The institute is part of Children’s Hospital of Wisconsin and is affiliated with the Medical College of Wisconsin, Marquette University College of Nursing and UW-Milwaukee College of Nursing.
Based on the concept of translational research, Children’s Research Institute is designed to take clinical problems from patients’ bedsides to the laboratory. Laboratory discoveries are then converted into new treatments, preventions, therapies and cures for patients. Early diagnosis of ARPKD affords the opportunity for maximal anticipatory care (i.e. blood pressure control) and in the not-too-distant future, the opportunity to benefit from new therapies currently being developed. If results are equivocal, genetic testing is available for both ARPKD and ADPKD. Specialized centers are now offering pre-implantation genetic diagnosis and in vitro fertilization for parents who have previously had a child with ARPKD. The first pre-implantation genetic diagnosis for a family at risk for ARPKD/CHF was conducted by Dr. Avner’s team and was a success.
In June 2013 Dr. Avner published New Approaches to the Autosomal Recessive Polycystic Kidney Disease Patient with Dual Kidney-Liver Complications in Pediatric Transplantation-June 17, 2013 www.ncbi.nlm.nih.gov/pubmed/23593929 . In the article they focus on new approaches to transplanting ARPKD/CHF patients and suggest that in a select group of ARPKD patients with recurrent cholangitis or complications of portal hypertension, combined liver-kidney transplant is a viable option. Although further study is needed to confirm their approach, they believe that combined liver-kidney transplantation can potentially decrease overall mortality and morbidity in carefully selected ARPKD patients with end stage renal disease and clinically significant CHF.
Dr. Avner’s goals for the next five years include establishing pediatric clinical trials for therapy of ARPKD/CHF in context of development of overall clinical trials program, increasing the volume of referrals to the ARPKD/CHF Clinic, and developing a new program of dual kidney-liver transplantation for a carefully selected subgroup of ARPKD/CHF patients. He and his team are truly the best and take the time to really get to know each patient and family. When living with a rare disease like ARPKD/CHF, it’s definitely a rare treasure to find doctors, researchers, and nurses who are so committed to understanding and treating our children on a day-to-day basis while also looking to the future for a treatment.
For more information about Dr. Avner’s work at Children’s Hospital of Wisconsin, or to make an appointment, call 1-414-337-7140.
