Idiopathic Pulmonary Fibrosis

This year, more than 40,000 Americans will learn they are dying of a disease they have probably never heard of. It kills as many Americans as breast cancer, and trends indicate it will soon be killing more. The condition is five times more common than Cystic Fibrosis or ALS.

Yet, if you ask people what IPF is, why do so few seem to know about Idiopathic Pulmonary Fibrosis, a progressive, deadly disease that kills in the silence of near anonymity?

Perhaps both the answer and the cause lie in the Catch 22 link between awareness and funding. It’s difficult to generate awareness without money, and difficult to generate funding without awareness. Even with equal or higher mortality figures, lesser known conditions tend to receive disproportionately lower research funding than those nearer the spotlight.

Last year, in federal funding alone, for every dollar that went to fight IPF, $2 went to ALS, around $4 to Cystic Fibrosis, and almost $33 for breast cancer. The last figure does not include millions from national cancer societies, business foundations, pharmaceutical and health equipment investment, private contributions and breast cancer-specific charities. Together, depending on how calculations are figured, estimated spending for breast cancer awareness, screening and research is somewhere between a billion and multiple billions per year.

This intense effort has boosted awareness, understanding of many aspects of the disease process, and to some extent, survival rates for breast cancer.

Meanwhile, at around thee cents each dollar, or possibly considerably less in funding compared to a disease that takes the same number of lives, IPF may soon be responsible for more deaths than breast cancer, following a recent spike in the number of new cases.

“IPF is a perfect storm of aging lungs, a genetic predisposition and continuing irritation,” UAB Director of Pulmonary, Allergy and Critical Care Medicine Victor Thannickal, MD, said. “Smoking and exposure to environmental irritants are risk factors. It’s more common in men than women and in people over 50.”

“At this point, the only treatment that offers any hope of extending life for a few years is a lung transplant, and only one person in 1,000 waiting will receive a transplant in time,”

Past approaches to treating patients with anti-inflammatories, corticosteroids and cytotoxic agents seem to have had no effect on survival. Supplemental oxygen eases labored breathing as lung tissues are scarred and harden, but most patients survive only two and a half to three and a half years after diagnosis.

Though much about IPF remains a mystery, and a great deal of research is yet to be done, scientists at UAB are beginning to learn more about the biological processes involved. A glimmer of good news recently emerged in Thannickal’s research to identified potential new targets for treatment in the signaling pathways involved in IPF.

“In healthy tissue, myofibroblasts assist with wound repair, and then die when their work is done. If apoptosis fails and they don’t die, a persistent repair process continues. This creates too much collagen, which causes stiffening and scarring of the matrix tissue. As the disease progresses, oxygen uptake in the lungs is increasingly impaired,” Thannickal said.

“It’s clear that in IPF, something in the wound healing process has gone awry. We identified two signaling pathways involved in controlling myofibroblasts that offer targets for treatment. The first is Rho-kinase, known as ROCK, and the second is a redox-signalling pathway involving NADPH oxidase, known as NOX4. We hope to partner with the pharmaceutical industry to develop small molecule inhibitors to block these pathways.”

One such inhibitor already exists. A Japanese stroke drug called Fasudil, a ROCK inhibitor, showed activity in blocking the enzyme in cell cultures and animal studies. However, it has been taken off the market and isn’t presently available.

“If we could isolate what it is about the drug that works, and find a way to reduce or eliminate the side effects, we would be a major step nearer being able to offer patients an effective treatment,” Thannickal said.

Learning to block the fibrosis process could also have a major impact in creating better treatments for other diseases. Fibrosis is a factor in many of the leading causes of death and disability, including liver, kidney and heart disease.

“In addition, understanding basic aspects of myofibroblast behavior and apoptosis resistance may be important in malignant diseases, as the stromal response may be critical to cancer progression,” Thannickal said.

It’s time to break the silence, to make people aware of IPF, and to speak up about the need for research funding. Finding a treatment for one disease could lead to a cure for many.