Valley fever researcher a pioneer in his field

January 30, 2007

By Flinn Foundation

When Dr. John Galgiani came to University of Arizona in the late 1970s, he stumbled upon the research opportunity of a lifetime.

A young professor in the area of infectious disease, Galgiani recognized that Arizona was host to a serious health problem that few people knew much about.

The problem was valley fever, a lung disease that affects 150,000 people nationwide each year.

With half of the cases in the country occurring in Maricopa County alone, Galgiani seized the chance to investigate at ground zero.

Today, after nearly 30 years of research and clinical work, Galgiani has become a seasoned expert on valley fever.

In that time, he has helped establish and direct the Valley Fever Center for Excellence, a research institute devoted to generating awareness, creating a vaccine, and developing a cure for the disease.

Taking a break from his full-time duties as director, researcher, and student mentor, Galgiani took a moment to talk with us about his work.

What initially sparked your interest in valley fever as an area of research?

Since my background training was in infectious diseases, when I first moved to Arizona in 1978, the obvious infectious disease that was present here was valley fever. Surprisingly, there was no concerted effort to study it, so I started doing clinical studies in my laboratory. There was so much that needed to be done that I had no problem continuing my research.

Could you briefly describe the symptoms of valley fever, and why it can be dangerous?

The fungus that causes valley fever, Coccidioides, creates spores which develop an infection after they’re inhaled. When this occurs, many people have no symptoms at all. Two out of three people will have an immune response that controls the infection without an illness, and go on to live a life completely immune to second infections. But that means that one out of three people will develop symptoms of some sort. Most of those people will develop a pneumonia because the fungus creates an infection in the lungs. And those symptoms are typically cough, chest pain, shortness of breath, weight loss, night sweats, fever, and fatigue.

Most times, this type of infection will resolve itself whether you treat it or not, but this process often takes many weeks or months. And those people, after resolution, will not get second infections either. A small percentage of people develop complications that are much more severe—for example, when the fungus goes in the bloodstream to other parts of the body like the bones, brain, and skin, the need for treatment is great. If this happens, you need to become good friends with your doctor, because most of the treatments we use last many months, to many years, to a lifetime.

Why is this disease of particular importance in Arizona?

Arizona is pretty much the epicenter for valley fever. It occurs as far north as Redding, Calif., and it has been found in Brazil, but it’s most centered in south central Arizona. When you add to that the population density in the counties of Maricopa, Pinal, and Pima, the number of people susceptible in those areas is probably two thirds of the entire country’s endemic regions. So this disease affects Arizona more than any other state in the country.

Why do you believe the number of reported cases has been on the rise?

Well, that’s a good question. I don’t think we really know for sure. There have been several trends over the last couple of years that might be responsible. We certainly have a population growth, but the epidemiology suggests that the raise in cases exceeds the simple explanation of a growing population. There might be climatologic factors that account for much of the change. In particular, last year we had essentially no rain all winter long, and during that period spores were still able to get into the air. So because of the drought, the seasonal peak we always have in October, November, and December had the opportunity to continue into the winter and into the spring. That may have been what happened last year. But I think it’s an area we can benefit from studying more precisely.%pagebreak%

Have you ever had valley fever?

I was one of the two-thirds of people who get valley fever without having the symptoms. I was actually studying valley fever actively and being surveilled with laboratory tests to find out when I would have it so that I could enroll myself as a subject. But it wasn’t to be, I was chagrined to find out.

Nikkomycin Z recently received “orphan status” from the FDA. What are the benefits of this distinction—how does it help you as a researcher?

Receiving orphan status allowed us two major benefits. First, we can apply for funds from the Office of Orphan Product Development—which we’ve done, and we are hopeful that that will lead to some funding for a clinical trial this year. We are waiting to get final approval, but we’ve gotten a very favorable review of our proposal. The second thing—and perhaps even more important for this drug in particular—is that if we receive FDA approval for using nikkomycin Z as a treatment for valley fever, we have seven years of protection so that no other entity can compete with us. Because nikkomycin Z was discovered in the 1970s, it has very old patent positions, and its intellectual property protection is fairly weak. So receiving this seven year protection as part of our drug development plan is very valuable.

You’ve estimated that it will take $40 to $60 million to get nikkomycin Z to the market (provided that all clinical trials are successful). How are you planning to get that type of funding?

The reason the Valley Fever Center for Excellence is now the sponsor for nikkomycin Z on the FDA’s Investigational New Drug files is because we couldn’t find a pharmaceutical company to assume the responsibility of sponsor. We hope to restart clinical trials that will produce new information which will make the drug less risky to develop, and therefore more attractive to a partner.

In spring of 2006, there was a lot of buzz about a UA spin-out company, Valley Fever Therapies LLC, that would work on a drug for valley fever. What has happened with this development since then?

It’s been created. Typically, when public universities have something of value, rather than to try to become a company themselves, they license it to another company. Since we want to participate in the development of the drug, Valley Fever Therapies will enter into a licensing agreement with the UA and the organization will then negotiate with any development partners.

If this drug turns out to be harmful or ineffective, where do you go from there?

If nikkomycin is harmful or ineffective, it shouldn’t go any further. It’s possible that related compounds could still be found. But in fact, we are hopeful that’s not going to be the case, because the target that nikkomycin goes after is an enzyme that fungi have but we don’t. So it could be a very selective target, which is a great characteristic of anti-microbial therapies. And all of the pre-clinical data on animals to date has failed to show any toxicity. This, of course, is always a question–that’s why you do studies to find out if there’s a problem with the drug–but nothing thus far suggests that a negative outcome is waiting in the wings.

Research is often a slow, painstaking process. How do you maintain your motivation on a day-to-day basis?

Well, you develop a skill for delayed gratification. You take pleasure in seeing patterns emerge, often one brick at a time. You understand where you want to go, and you plot strategically. I think it’s a skill that you either learn or you don’t. Some people actually prefer to be on the front end of things because they have other skills or enjoy other things. But other people like see the whole pattern emerge.

What hand do you have in the Valley Fever Center’s day-to-day operations?

The Valley Fever Center for Excellence was approved by the Arizona Board of Regents in 1996 to promote education, research, and patient care in this disease. As director, I have tried to increase in all three of the state’s universities the number of faculty who actively participate in that mission. My own research and clinical work in vaccine development and promoting human studies with nikkomycin Z is included in center activities, but there are also nearly a dozen other independent faculty doing a variety of other things.

Why do you consider your line of research worthwhile?

It’s been gratifying to work in an area which was so clearly in need of research. I’m excited to see attention and work increasing on the disease. I think we still have a lot of work to do, but I like the trend.

What is your biggest hope for the future?

I guess my biggest hope would be that several diverse communities within the state would own this disease—that the medical community would participate in producing the highest standards of quality healthcare, and that the research community would find ways to understand this disease and the ecology of the fungus more completely, which might lead to more strategies for its control. I also hope that the state government and philanthropic organizations would realize the importance of participating in helping with those activities.