Mayo Magazine

Endowment in Action

A scientist applies his work to patient care in an extraordinary way. A physician theorizes a new use for an old drug to help a common condition in the elderly — and then proves it. A unique program helps shape a promising student's future and her vision for advancing medicine.

Those plotlines are part of an inspiring story unfolding every day at Mayo Clinic. It is the story of the Mayo Clinic endowment in action.

Many funds, most of which come from benefactor-designated gifts, make up the endowment, a pool of money that's invested for the future. Each year a portion of the income that comes from the endowment is distributed to physicians, scientists and students to support innovative research and education activities, all with the goal of advancing patient care.

This support has a power that extends far beyond balance sheets and the individuals who receive funding. In research, this funding creates a flexibility that vastly expands the abilities of physicians and scientists to make discoveries and to collaborate to improve patient care. In education, the endowment helps Mayo recruit the best young minds by keeping tuition low and by funding innovative programs. For these reasons, endowment funding will be one of Mayo's most important philanthropic priorities for many years to come.

A bridge between science and patient care

" ... funding from the Roberts' endowment means a significant portion of my laboratory budget is covered ..."

– Larry Pease, Ph.D.

The disease fighter that immunologist Larry R. Pease, Ph.D., has developed is a potential revolution in the making. It's a human antibody with potent abilities to direct the body's immune system. Dr. Pease's laboratory tests show the antibody, nicknamed Lymph12, can mobilize the body's immune system with unheard of speed, seeking out and destroying cancerous cells and small tumors. Equally important, Lymph12 produces this extraordinary result without many side effects commonly seen in powerful immune system responses.

"We haven't seen a bad consequence from our treatment so far," Dr. Pease says. "Immune therapy strategies often set off secondary effects, like swelling in the spleen and lymph nodes or destruction of normal cells. We don't get any of that with Lymph12. Our studies indicate that it doesn't change the normal regulation of the immune system, and that's why we think we're seeing fewer side effects."

Dr. Pease and a team of clinicians, headed by Svetomir Markovic, M.D., Ph.D., are designing a clinical trial to test the antibody as a treatment for advanced stage melanoma, and he's hopeful it will launch later this year. In addition to showing promise as a cancer therapy, Lymph12 has demonstrated exciting possibilities as a treatment for allergic asthma. In laboratory studies, the antibody redirects the immune system's response to allergens, preventing swelling in the lungs and other hallmarks of allergic asthma.

Lymph12's discovery is directly linked to endowment funding, says Dr. Pease. His research is funded in part by the Joe and Ruth Roberts Endowment for Allergy and Immunology Research. The Roberts' funding is important because of the flexibility it provides.

"The fact that I have funding from the Roberts' endowment means a significant portion of my laboratory budget is covered, and I don't have to go out and look for funding," says Dr. Pease. "The downstream consequences of that are immense. It frees up my time so I can broaden my horizons and see what's going on around me. And that's exactly what happened in the case of Lymph12."

With that time, Dr. Pease collaborated with physician colleagues, Moses Rodriguez, M.D., and Robert A. Kyle, M.D., both of whom are widely known for their research in diseases of the immune system, such as multiple sclerosis and multiple myeloma. Evaluating blood samples collected from hundreds of patients with these diseases revealed insights that allowed Dr. Pease to develop Lymph12.

In fostering these types of collaborations, the Roberts' fund and other endowments form an important bridge, which Dr. Pease says is necessary for scientists to maximize their ability to contribute to patient care.

"We live in a technology-rich environment," Dr. Pease says. "We can do things in the lab now that a few years ago seemed like science fiction. With the opportunity to find out what my physician colleagues are doing, I can bring my expertise into play in a way that's relevant to treating patients."

A "smart drug" idea

"The most exciting studies are often ones where you have this idea that you conceptualize and you need to test it."

– Phillip Low, M.D.

Orthostatic hypotension, a syndrome that causes a sudden drop in blood pressure when a person stands up, affects a broad group of patients. It's especially common in people over age 70, but it's also associated with a spectrum of diseases, such as diabetes, heart disease and several neurological disorders. This sudden pressure drop is potentially dangerous, causing dizziness, blurred vision and fainting.

Although there are ways to manage the disease without drugs, medications are necessary for some patients, which presents a thorny problem, says Phillip A. Low, M.D., a neurologist at Mayo Clinic. He has spent more than 30 years studying the autonomic nervous system — the system that regulates blood pressure, digestion, breathing and many other essential functions.

"Previously, the only drugs to treat orthostatic hypotension increased blood pressure, which increased a person's risk of stroke, heart attack and so on. What we needed was a 'smart drug' that would increase blood pressure only when patients stood up," says Dr. Low.

Dr. Low and his colleagues thought that such a drug might already exist: a medication called pyridostigmine, used to treat myasthenia gravis – a nerve disease that disrupts communications between nerves and muscles.

Pyridostigmine enhances functioning in an area of nerve cells called the autonomic ganglion, which is largely inactive when a person is lying down. When a person stands, signals between nerve cells increase in this area, so Dr. Low and colleagues theorized that pyridostigmine might raise blood pressure when a person stands.

Endowment funds helped Dr. Low and his colleagues investigate this promising idea. With support from the Michael and Cathy Schultz Neurosciences Endowment Fund, Dr. Low performed a successful pilot study of the drug in 15 patients with orthostatic hypotension.

These findings helped secure funds from the National Institutes of Health (NIH) for a larger study to more thoroughly evaluate the treatment. Follow-up results from the study, reported earlier this year, were dramatic: 20 months later, 75 percent of the patients in the study reported either good or excellent results from the treatment, which was evaluated both alone and in combination with existing medications, and about 25 percent were able to manage their symptoms with pyridostigmine alone.

This journey from hypothesis to proven results highlights another important aspect of the endowment's influence on research and patient care, says Dr. Low.

"The most exciting studies are often ones where you have this idea that you conceptualize and you need to test it," he says. "This is where the endowment is critically important. We can screen ideas to see whether they are likely to be successful, and secondly, to see if they can generate preliminary data to get NIH funding. The endowment really serves a unique role."

Creating future leaders in science

"The fellowship is helping me to see things outside my normal environment, my normal mode of thinking ..."

– Becky Schmidt

She is only beginning her studies at Mayo Graduate School (MGS), but Becky L. Schmidt, a second-year doctoral student studying cell biology, has already secured a place in Mayo Clinic history.

Ms. Schmidt is the first recipient of the Pobanz Family Endowed Predoctoral Fellowship. Established last year with an estate gift from Grace and Wilbur Pobanz and their daughter, Sandra Pobanz, of Moline, Ill., the fellowship is the first in the 20-year history of MGS dedicated solely to the training of scientists in the school's Ph.D. programs. The gift will broaden Ms. Schmidt's education at MGS by providing funding for additional coursework and for attending professional conferences, both of which are invaluable for a predoctoral student, she says.

"The fellowship is helping me to see things outside my normal environment, my normal mode of thinking, you could say, and I'm applying it to what I'm doing," says Ms. Schmidt. "It's enhancing the education I'm getting at Mayo and giving me a nice plunge into the scientific community."

Ms. Schmidt has already made quite a splash in her local scientific community, says her mentor and supervisor at Mayo, Amy H. Tang, Ph.D., whose lab is studying cell biology in two important contexts: to develop new strategies for blocking the growth of cancer cells and to halt septic shock, a potentially deadly syndrome that develops in the wake of overwhelming infections.

"Becky's only been in my lab for a year, but we're already submitting papers for publication based on her work," says Dr. Tang. "She's the best student any principal investigator could hope for; she is very talented and driven and she loves the research she is doing. If we give her all the ingredients, she will succeed."

"The value of this support is incredible ... This puts them [students] on an early track for success and helps them launch their careers. The impact of these endowment gifts is very long-lived."

– Diane Jelinek, Ph.D. Dean of Mayo Graduate School

Diane Jelinek, Ph.D., dean of MGS, is hopeful that many more endowed predoctoral fellowships will be established as a way to give students of Ms. Schmidt's caliber the same enrichment opportunities. Dr. Jelinek says endowment support for the graduate school has both immediate and long-term benefits. In addition to sponsoring the education of future leaders in research, it also helps investigators staff their laboratories with bright, young researchers.

"The value of this support is incredible," says Dr. Jelinek. "While the students are training, they are helping our scientists make advancements that are directly relevant to the treatment of diseases. This puts them on an early track for success and helps them launch their careers. The impact of these endowment gifts is very long-lived."