PRIM&R is pleased to welcome Andrea Amalfitano, PhD, DO as the keynote speaker at the 2010 IACUC Conference in Baltimore later this month. On Monday, March 22, Dr. Amalfitano will commence the conference program with a discussion titled, “Biomedical Research into Treatment of Genetic and Infectious Diseases.”

Dr. Amalfitano is the Osteopathic Heritage Foundation Endowed Professor of Pediatrics, Microbiology, and Molecular Genetics at Michigan State University (MSU). As a clinical pediatrician and geneticist, Dr. Amalfitano sees patients and families who are affected by a multitude of diseases for which there are no cures.

As a result, he has set out to pursue basic biomedical research in an effort to help these situations. For one particular project, he co-led a team using the first-in-man therapy for a muscular dystrophy known as Pompe Disease. As a result of that pioneering trial, Myozyme is now an FDA-approved drug for the treatment of all patients with Pompe Disease. In addition, Dr. Amalfitano’s research laboratory has attempted to focus its efforts upon determining the feasibility of gene therapy to cure human genetic and non-genetic diseases, and to eventually translate that knowledge into the clinical realm.

PRIM&R Staff (PS): Can you tell me a little bit about your planned remarks?

Andrea Amalfitano, PhD, DO (AA): One topic I plan to address is the relationship between my clinical activities and my basic lab research. These two aspects of my work are intertwined, in that I am constantly applying findings from one arena to the other.

PS: In addition to talking about your research, can you share a bit about the kind of advice, strategies, and direction you will be providing the audience about the ethical and policy issues related to gene therapy or other cutting-edge research?

AA: There are many fantastic lab-based studies, but quotes from scientists claiming the science is close to clinical application, such as “we are 2-5 years away from clinical use,” more often than not mean the scientists do not have a clue when the research will reach this stage.

There are so many steps to bringing the science to the patient. Gene therapy is a classic example. Early on there were wild claims about revolutionizing medicine. I was in the middle of this, and was more naïve than I am now. Unfortunately, I now see these same claims being made in regard to the “potential” of various stem cells.

There needs to be a greater understanding on the part of the laboratory scientists in regard to the complexities of translating findings made in a research laboratory into clinical reality. In my experience, there is a great disconnect. If scientists are not involved with patient care, they many times are not aware of the multiple practical problems (scientific, medical, as well as pragmatic) that are associated with bringing the research observations (and their potential applications) into clinical fruition.

PS: Since the March audience will be primarily composed of those who are working with animals, how would you characterize your experiences with Michigan State’s IACUC? Such as, have you found them to be educated about and sensitive to the highly technical and sensitive nature of your work? Have you found their responses to your protocols reasonable?

AA: I think I’ve been able to see all the facets of this issue. I sat on an IACUC for eight years and am very familiar with this side of the equation of doing animal research. While I see the strengths and weaknesses of IACUC oversight, the bottom line is that the necessity is there.

If we desire to move novel, cutting-edge applications into human use, we need to minimize the numerous risks involved. We always consider computer modeling, tissue cultures, and other types of alternative strategies in these sorts of studies. Only when these systems fall short are we justified in moving into animal models. Our specific type of research combines genetic technology with genetic diseases interacting with a living, extremely complex immune system.

These complexities are not matched by current computer models or tissue culture systems. Animal models are the next best option. However, we are always conscious about humane end points, and thus research animals are always treated in a safe and benevolent manner.

My experience with the IACUC is that they offer valuable education to researchers and provide alternatives that will foster both the acquisition of important research results, alongside the ethical treatment of animals. I see this as a win-win situation. It’s a necessary part of doing research. If you want to really make a difference, these are the hurdles we must overcome.

PS: As PRIM&R’s mission is to advance ethical research, and as the fields in which you are working represent the cutting edge of research, what do you consider to be the most challenging ethical issues when moving from the lab to “first-in-human” studies?

AA: I teach a course about translational medicine. If there’s a great clinical need and the risk suggests it’s reasonable, this leap can sometimes be made without fully understanding the molecular mechanisms of a putative therapy. This empiric approach has its limitations, as each clinical situation is a moving target, and every situation is unique. There are many variables at play to decide whether you are ready to make that jump.

PS: Do IRBs and regulations guide that process effectively?

AA: I think so. I have been on IRBs in the past and understand how they work. The process, while it might seem cumbersome, is absolutely necessary. It’s important to instill the public with trust. There were a couple cases in the late 1990s where I feel this public trust was breached, but IRBs and clinical researchers responded appropriately by becoming more diligent. The process has to be vigorous.

PS: Thank you for taking the time to speak with us, Dr. Amalfitano. We look forward to hearing more about your exciting work at the 2010 IACUC Conference later this month.