Impact Stories

What is gene therapy?

Gene therapy is a mechanism to treat disease using viruses to deliver genetic information into cells. This might sound counterintuitive because viruses are responsible for causing disease. However, a virus is an ideal vehicle to create gene-based therapeutic treatments precisely because it can efficiently transfer genetic information into cells. In viral-based gene therapy, viruses are de-engineered from being harmful and re-engineered to deliver beneficial chemicals to the body as treatment.

In my research, we have developed improved viral vehicles or “vectors” in the lab to potentially treat rare genetic diseases, infectious diseases and cancer safely and with minimal side-effects. One of the challenges with gene therapy is when the genetic material is delivered, the body views it as foreign and wants to reject it, so the immune system must be suppressed, which has negative consequences for quality of life. To counter those adverse effects, we also study how viruses interact with the immune system to stimulate the body’s healing response. The unintended consequence of conventional medicine is healthy cells are often killed alongside disease-causing cells. In contrast, treatments using the immune system target only the “invading” illness, preserving all the healthy cells. The beauty of using the immune system is it harnesses the body’s natural capacities for healing.

What scientific discoveries have been made by the Amalfitano research team at Michigan State University?

Creating technology to de- and re-engineer viruses into safe, effective and scalable gene therapies is the lab’s primary contribution to science. Adenovirus is the virus that causes the common cold. Our lab found it can be de-engineered and re-engineered to safely target numerous organs and body systems as a treatment for a variety of inherited and acquired diseases. First, we de-engineer the Adenovirus by removing the genetic material that causes illness. Then we re-engineer it with the genetic information that treats illness. This process of de-engineering and re-engineering viruses provides a foundation for many applications. Our lab does the early-stage development of this technology and then we partner with the pharmaceutical industry to develop, test and manufacture medications and make them available for use in patient care.

How does your work in genetics at the cellular level benefit patient care?

As a physician researcher, I see the patient experience firsthand and how conditions and diseases play out in real life. I want to make scientific discoveries that make an impact on the patient’s quality of life sooner rather than later. Studying genetic diseases at the cellular level provides an opportunity to identify interventions that can be applied early in the treatment of a disease by directly influencing the pathways causing the disease.

For example, our first application of this technology was for the treatment of Pompe disease, a rare genetic disease. In its most serious form, it appears in newborns, but it can present even in adults. It causes progressive muscle degeneration and weakness, and ultimately affects the heart and lungs, causing premature death. In our lab, we studied how to use the Adenovirus to target the gene responsible for causing Pompe disease.

This technique was then applied to infectious diseases that are difficult to treat, like C. difficile, a bacterial infection that causes diarrhea and can be especially dangerous for older adults. It has also been used to develop drugs and vaccines for the treatment or prevention of diseases like HIV, malaria, and most recently, COVID-19.

This technology is also being applied to cancer treatments, where it is called immunotherapy. Because it is a relatively new treatment, immunotherapy is currently the last line of defense for difficult-to-treat solid tumor cancers like colon and pancreatic cancer. However, the results are proving immunotherapy can be an effective treatment. There are now many late-phase clinical trials underway evaluating the immunotherapy we invented, and its benefit early in treatment as a first line of defense in the treatment of cancer, instead of the last line. These types of trials are the final step prior to FDA approval and widespread use.

These are examples of the kind of translational research our lab conducts to find new treatments and cures for diseases. Translational research focuses on “bench to the bedside,” ensuring science conducted in the lab, or the “bench,” is conducted with human health, the “bedside,” as its primary objective. The goal of translational research is to advance patient care.

How does conducting your research at a College of Osteopathic Medicine, and the osteopathic profession’s focus on treating the whole person, influence your work?

One of the core tenets of osteopathic medicine is the body is capable of self-regulation, self-healing and health maintenance. Our work focuses on using the body’s own natural defenses – the immune system – to treat disease. The holistic perspective of osteopathic medicine and its treatment of the whole person is a systems viewpoint, and we are increasingly learning that when it comes to systems in the body, the immune system is everything. Like the practice of osteopathic manual manipulation, where osteopathic-trained physicians use their hands to stimulate the body’s immune system to heal itself, our work sparks the immune system at the cellular level to provoke a healing response.

How has the funding investment from the Osteopathic Heritage Foundation helped you impact patient care?

The Osteopathic Heritage Foundation Endowed Professorship in support of the Center for Neuromusculoskeletal Research allowed me to come back to my alma mater, Michigan State University, and contribute to developing the next generation of physician scientists through the same DO-PhD program from which I graduated. Currently, five DO-PhDs will have been trained under my mentorship as a PhD advisor.

The endowment also supports development of our research program, allowing us to expand the lab and move beyond virus work to look more closely at the immune system. As we continue to understand how genetics influence the immune system, it opens new avenues of understanding for other diseases. These early-stage findings can then be developed into drugs and therapeutic vaccines and tested in clinical trials. The endowment has been especially helpful in supporting research for rare conditions and difficult-to-treat diseases, which typically receive less investment from traditional funding sources. All these efforts have contributed to advancing patient care.

What is next for your research?

The lab’s current work looks at genes associated with autoimmune diseases, which are caused by an overactive immune response. The hypothesis is that by understanding the impact these genes have on the immune system, new and effective treatments for these diseases can be developed at the immune-system level.

Our most recent work is focused on two autoimmune neuromusculoskeletal diseases: ankylosing spondylitis and multiple sclerosis. Ankylosing spondylitis (AS) is an inflammatory disease which, over time, can cause bones in the spine (vertebrae) to fuse, making the spine less flexible. It can also affect the ribs, causing difficulty breathing, and predisposes patients to inflammatory bowel disease and inflammatory eye symptoms. Multiple Sclerosis (MS) is a disease of the brain and spinal cord where the immune system attacks the protective covering of nerve fibers. It is a debilitating disease that interferes with the delivery of messages from the brain to the rest of the body and can cause permanent damage or deterioration of the nerves.

It turns out, genetic diseases such as AS and MS share genes that increase an individual’s susceptibility to develop these and other autoimmune diseases. Identifying how inherited genes change the immune system and predispose some people to having a hyperactive immune system can be used to develop new and innovative treatments allowing people living with these conditions, and potentially many others, to have better health outcomes and quality of life.