Renowned Pulmonary Fibrosis Researcher Seeks Answers Before Hanging Up His Lab Coat

74-year-old Lung Disease Doctor Not Giving Up Now Even After 40 Years of Searching

DENVER, Jan. 28, 2013 /PRNewswire-USNewswire/ -- Dr. Marvin Schwarz isn't ready for retirement, though several years ago, he stepped down from his position as head of the Pulmonary Sciences Critical Care Medicine Division at the University of Colorado Medical Center. Schwarz, a 74-year-old pulmonologist and lung disease researcher hasn't found what he's been looking for despite more than 40 years of searching -- the cure for the deadly lung disease he began investigating at the dawn of his career, a progressive and fatal disease that causes scarring of the lung called Pulmonary Fibrosis (PF). 

PF has no FDA approved therapies and no cure and claims as many lives each year as breast cancer but unlike its survival rate of approximately 80 percent, PF has virtually no survivors.

Schwarz has treated thousands of patients with PF and he's seen patient after patient succumb to the relentless lung disease that continues to keep him up at night. In 2001, Schwarz was a founding board member of the Coalition for Pulmonary Fibrosis, a non-profit organization primarily focused on patient support and supporting research efforts.

Before he hangs up his lab coat, Schwarz says there are some things he wishes for and wants. "I want to be able to predict which patients are at the highest risk.  I want to be able to find those patients via various testing like blood tests and CT scans," he said. "And I want to find a drug that catches this early in the process and stops it in its tracks."

Pioneer and Father of PF Research

Schwarz' personal commitment and his insistence of other researchers to remain committed despite decades of little progress in the disease is finally beginning to pay off.  Much activity is taking place in the space today, at least in part, to Schwartz' early and continued work.   Today, the PF landscape includes many active drug trials, including two Phase 3, and a multitude of bench to bedside research projects in pulmonary fibrosis, the largest and most deadly of 200 diseases that fall into a category known as interstitial lung disease.

"Marvin's commitment to better understanding of the causes and treatment of interstitial lung disease has been without peer. In addition, he spawned a generation of others interests in the disease," said Talmadge E. King, Jr., MD, Chair, Department of Medicine, University of California, San Francisco and PF expert.

During his early years as a researcher, in the 70s and 80s, while much research attention was moving towards cancer, Schwarz kept his focus in ILD and encouraged other researchers, many of them his students at one time or another, to do the same.  Most researchers would have probably retired by now – either out of exhaustion or frustration.

"Marvin has been a relentless advocate in the field of pulmonary fibrosis, influencing countless patients, clinicians, and investigators, all of whom have benefited from his tremendous efforts.  His leadership and dedication to the field has personally inspired me to pursue a career in interstitial lung disease, despite the difficult challenges in caring for patients and a lack of clarity in its etiology," said Gregory P. Cosgrove, MD, FCCP, Assistant Director, Interstitial Lung Disease Program, Associate Professor, National Jewish Health & University of Colorado-Denver. 

"Marvin's renewed research efforts will enhance our understanding of the pathobiology of pulmonary fibrosis. Perhaps more importantly, these achievements may be surpassed by the contributions of the generations of physicians and scientists he has trained, ensuring his goal that a therapy for this devastating disease will be identified, said Cosgrove.

Known for his dry wit and somewhat gruff nature, Schwarz is highly regarded by his former students.

"Marvin was my fellowship director and taught me much of what I know about interstitial lung disease. More importantly, however, he taught me how selfless leadership and a sense of humor can achieve great things," said Harold Collard, Associate Professor of Medicine
Director, Interstitial Lung Disease Program, University of California, San Francisco.

Awarded Doctor

Published in more than 300 articles, and recipient of numerous career awards including the prestigious Trudeau Medal by the American Thoracic Society (ATS), Schwarz' research has spanned the gambit of the current and past understanding of the lung disease.

"Marvin Schwarz has had a long and distinguished career helping patients suffering from ILD, teaching physicians the best therapies for this condition, delving into its root causes and clinical characteristics, all while attempting to find its cure," said James F. Donohue, MD, Professor of Medicine at the University of North Carolina, School of Medicine, Department of Medicine and Chair of the Foundation of the American Thoracic Society.

New Lease on Research Life

Enter a younger researcher who has energized the elder researcher to not only stay in the research game but convinced him to work alongside him.  David Schwartz, MD, a pulmonologist who is probably best known for his work in the genetics and genomics area of lung disease and in particular in PF, started the first genetic research program in the disease in the late 90s at Duke University Medical Center.

Today, Schwartz works with Schwarz at a new lab after collaborating with him from nearby National Jewish Health for a few years.  Schwartz decided to move his lab officially over to the University of Colorado where Schwarz has spent most of his illustrious career.  The two have expanded their combined research efforts and believe they are on to something big. 

The two men focused on genetic research in PF and together, with a team of researchers, made one of the few major discoveries in the disease history.  Published in the New England Journal of Medicine, their research found that a renegade protein called MUC5b that regulates mucus in the lungs – and when present -- tells a story about the mortality of the patient. 

Present in more than two thirds of patients with PF – sporadic forms as well as genetic or familial forms of the disease – the gene variant carries both good and bad news.  The good news is that patients with MUC5b tend to live longer than those who don't have the variant.  The bad news is that patients who have a familial history of the disease have a six to 20 fold increased risk of developing the disease depending on whether they have one copy or two of the variant.  

Mucus is a vital part of lung biology, protecting delicate cells from direct exposure to inhaled irritants and toxins, and helping to clear them from the lungs. The researchers hypothesize that excess mucus production caused by the MUC5B variant could slow clearance of mucus contaminated with irritants and toxins. Excess mucus might also interfere with repair of air sacs damaged by these contaminants. Another scenario suggests that the genetic variation could trigger the production of mucus in areas where it is not normally present.

A New Way of Doing Things

Schwarz says some of the issues that previous PF drug trials have had and current ones continue to face are related to the lack of recognition of phenotypes – and that creates confusion as to which drugs work on which patients. 

Based on recent clinical trials, clearly some drugs are working on some people, he said, but identification of characteristics of individuals where drugs seemed to work that would benefit that subpopulation has been elusive. "It is likely that even in negative trials, there are some patients who do have the desired response.  But at the present time we don't know how to identify those patients," Schwarz said.

It is Schwarz and Schwartz' work together that may indeed help develop simpler ways of phenotyping that can be applied to all PF trials – or the use of information such as age, sex and smoking history along with results of a high resolution computer topography (CT) scan. "We have to look back and forward," said Schwarz. "We must look at old studies – the genotype cause of PF and response to treatment and look at lung specimens and the gene expression profiles and we must look at the pattern of gene signatures."

No Treatment Doesn't Mean No Way to Treat

Schwarz says having no approved treatment doesn't mean there is no way to treat patients.  If you look at survival studies as compared to 30 to 40 years ago, he says, people are living longer with PF.  Doctors now use oxygen therapy, treatment for reflux disease, treatment for sleep apnea and put patients in physical and pulmonary therapy programs as well as lung transplantation for some, Schwarz said.  Treating these comorbid areas, according to Schwarz, helps survival, though it isn't directly treating the fibrotic process.

"There are a lot of things you can do to improve people's lives – their quality of life and their extent of life.  We know what helps people in general.  We can improve their outcomes.  That is one thing we have learned in the many years." 

Though Schwarz has still not solved the puzzle PF presents, he says the answer is closer than it has ever been. But, "answer" is a pretty general term, he says. "I think our understanding is greater.  In lieu of [a cure], we may come up with new targets for therapeutic intervention and much earlier detection."

SOURCE Coalition for Pulmonary Fibrosis



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