Finding a Cure for Kidney Disease

Editor Laura J. Pinzon Director, Business Operations Photography UM Biomedical Communications Jenny Abreu Design, Editorial and Project Management Spark It Communications, Inc. Published by the Chairman’s Office of the Department of Medicine at the University of Miami Miller School of Medicine. All contents, ©2022 University of Miami. Reproduction in whole or in part without previous written permission by the editor is prohibited.

TABLE OF CONTENTS

Chair’s Message Finding a Cure for Kidney Disease A New Generation for Regenerative Medicine

1 2 6

Researchers Develop Promising Treatment for Rare Genetic Syndrome 10 By the Numbers 16 New Division Spotlight 19 Division Highlights 20 Philanthropy 50

Chair’s Message

The Department of Medicine has arrived at a juncture where our impact on medicine and science has reached a critical level, enabling us to spark new therapies and diagnostic modalities to cure human disease and improve the human condition.

We are Sparking Innovation in the diagnosis and treatment methods used to prevent and cure diseases, such as those of the endocrine system, kidney and heart. As Chairman, I am proud of how the Department of Medicine has been a flourishing academic department by nurturing growth of our junior faculty and addressing health disparities. I am certain we will continue on this trajectory for years to come.

Our longstanding partnerships with Jackson Memorial Hospital, one of the largest teaching hospitals in the United States, and the Bruce W. Carter Department of Veterans Affairs Medical Center, allows us the opportunity to be at the forefront of extraordinary discoveries that will result in improved health outcomes for our patients.

Welcome to the 2022 Annual Report of the Department of Medicine at the University of Miami Miller School of Medicine.

Only my best,

Roy E. Weiss, M.D., Ph.D. Professor of Medicine Chair, Department of Medicine Kathleen and Stanley Glaser Distinguished Chair in Medicine Rabbi Morris I. Esformes Endowed Chair in Medicine and Endocrinology University of Miami Miller School of Medicine

Finding a Cure for Kidney Disease

Kidney disease is a silent killer for millions. The two bean-shaped organs, built to filter excess water and waste out of the blood, fizzle and fail when their own purifying system stops working. While unresolved high blood sugar and high blood pressure are the most common causes of renal disease, better recognition and management of these factors have not been able to reduce the rising prevalence of kidney failure, which is considered a silent killer since many people don’t realize they have kidney disease until it’s very late. For more than a century, the situation has baffled and frustrated physician-scientists and patients alike. More recently, several new drug discoveries offer new hope for the future of patients with the disease.

Alessia Fornoni, M.D., Ph.D. Alessia Fornoni, M.D., Ph.D., along with Sandra Merscher, Ph.D., and colleagues at the University of Miami Miller School of Medicine, Department of Medicine, not only identified a new mechanism responsible for kidney disease, they’ve discovered a solution that could be the key to managing – and ultimately curing – kidney disease. “The kidney is a very complex organ that allows you to see the big picture, to see the whole body, because of its multiple functions,” says Dr. Fornoni, Professor of Medicine and Molecular and Cellular Pharmacology, Chief of the Katz Family Division of Nephrology and Hypertension, Director of the Peggy and Harold Katz Family Drug Discovery Center, Co-Director of the Miami Medical Scientist Training Program (MSTP) and Module Leader of the Clinical and Translational Science Institute (CTSI).

Cells called podocytes act as microscopic worker bees for the kidneys’ filtration system, regulating the process to flush out toxins and retain proteins. When those cells are damaged, however, waste accumulates, scars form, and patients face dialysis, transplantation, or sometimes death. What has never been clear is what exactly damages these cells. Since the 1800s, physicians have known that fat can be present in the kidney’s filtering system. Not until recently, however, have researchers realized that too much fat actually damages these podocytes and contributes to the progression of kidney disease.

In 2010, Dr. Fornoni and her team began collecting data that showed the cause-andeffect relationship between fatty podocytes and renal failure. Their work was later published in the peer-reviewed journals Nature Communications and the Journal of Clinical Investigations. From there, they began developing strategies to understand why these cells become fat under conditions of stress (i.e., diabetes) or in other forms of chronic kidney diseases), and more importantly, how to reverse the implications.

“Science is beautiful because it reveals new, unexpected and exciting Sandra Merscher, Ph.D. knowledge as you go,” says Dr. Fornoni, who emerged from a rural Italian village to become a worldrenowned nephrologist. “The question is, how do we bring it back to the community, to the “Having reached Phase 2 trials, the probability that Dr. Fornoni’s discoveries will change the life of millions of kidney disease patients in the near future is much more tangible than ever before.”

patient? The best way is to generate disease awareness and build new safe and effective therapies for the prevention and cure of kidney disease.”

In an initial attempt to reduce fat content in the kidney, Dr. Fornoni’s team found that cyclodextrin, a molecule that consists of several sugars, has the power to break down existing cholesterol. Because the molecule counters lipid buildup, it effectively puts “chubby” cells on a permanent diet. Clinical studies are underway to prove injectable cyclodextrin’s efficacy in affected patients. With the support of the University of Miami Miller School of Medicine, Dr. Fornoni and her colleagues have been able to patent their discovery and subsequently license that patent to ZyVersa Therapeutics for further clinical development.

The downside of an injectable form of cyclodextrin is that patients who suffer from chronic kidney disease will require frequent injections. For many, this schedule is untenable. This is why Dr. Fornoni and her team, in collaboration with Hoffman-La Roche, a leading research-based healthcare company, embarked on the discovery of a new oral agent also capable of reducing fat content in kidney cells. This agent, named R3R1, is being tested in a worldwide Phase2A trial by River 3 Renal Corporation, a developer of renal disease therapies that Dr. Fornoni founded in 2020.

These studies, which are now approximately four to five years away from finding a kidney disease drug that’s worthy of hitting the market, took at least 15 years of work to get where they are today, Dr. Fornoni explains.

“My goal is to continue to work in drug discovery towards finding a cure for the millions of patients affected by kidney disease. If drug 1 doesn’t work, I want to go on to drug 2 or drug 3 or try another alternative, but I have no doubt these pathways are the proper target,” she says. “I have continuous NIH funding since 2008 to study the mechanism by which these lipids accumulate, and I’m very grateful to the National Institutes of Health and to several patient foundations (Alport Syndrome Foundation and Nephcure Kidney International) for supporting our commitment to understanding kidney disease.”

Dr. Fornoni adds: “At the same time, I can’t wait until the mechanism is totally sorted out so that we, in collaboration with industry partners, can find a drug that works. This is why working in a supportive research environment, such as the University of Miami, has allowed us to accelerate our discovery to benefit patients and the community at large.”

A New Generation for Regenerative Medicine

Regenerative medicine is flourishing under the well-scoped eyes of physician-scientists at the University of Miami Miller School of Medicine’s Department of Medicine. Cell-based therapy – the use of cells to stimulate the regeneration of damaged tissue and repair the mechanisms underlying disease – is their focus. It’s a game-changer for treating chronic conditions, such as diabetes, Parkinson’s disease, heart disease and arthritis, disorders which all have something in common – a limitation in the body’s ability to self-heal.

Joshua Hare, M.D., Chief Sciences Officer, Senior Associate Dean for Experimental and Cellular Therapeutics, Director of the Interdisciplinary Stem Cell Institute (ISCI), and Louis Lemberg Professor of Medicine at the Miller School of Medicine, says the collaborative nature of the research allows University faculty “to have an impact nationally, not just here on campus.”