The University of Texas at San Antonio has three high-profile diseases in the crosshairs of its microscope, and Professor and Dean of College of Sciences George Perry wants to see effective treatments emerge in this generation.
“We all hope to have a cure,” Perry said. “But those are really hopes.”
More likely, he said, the scientists working at UTSA will be able to make strides in prevention and treatment to reduce the morbidity associated with Alzheimer’s disease, cancer, and tularemia.
Scientists’ pursuits have added value to the teaching at UTSA, as all of the studies involve students in various aspects. Having them involved in studies that are relevant “shows them the practicality of scholarship,” Perry said.
The research teams include students at all levels, with a variety of career goals. While only a portion of the students participating in the research will go on to be scientists themselves, all of the undergraduates are being introduced to inquiry, Perry explained. In the real world, the skills students learn in cross-disciplinary research will be more suited to the jobs they pursue.
“The modern economy favors people who have creative thoughts,” Perry said.
Because of the high value of hands-on experience outside the confines of rigid fields of study, Perry sees research as invaluable to university education.
“Research and teaching are not separate missions,” he said.
Alzheimer’s Disease
Perry himself has published around 1,000 pieces on Alzheimer’s disease, making him the nation’s leading Alzheimer’s researcher. He is currently the editor-in-chief of the Journal of Alzheimer’s Disease.
Alzheimer’s affected 5.5 million Americans in 2017, with only four FDA-approved drugs to treat the disease. Those drugs, Perry said, do little other than treat some of the symptoms of the degenerative disease. He questions the premise behind current Alzheimer’s treatment, which focuses on a correlation between plaques in the brain and the onset of the disease. Perry believes that there is a relationship, but not a causal one. Plaques, he said, may be a byproduct of biological processes aimed at protecting the brain. After 30 years and $24 billion invested in efforts to reduce plaques, Perry’s hypothesis is controversial. Investment, however, cannot truncate the scientific process.
“Science is tentative,” Perry said. “Once you believe something, it isn’t science.”
He has debated other researchers and is currently in the lab working with a mass spectrometer to study the metals present in plaques to test his hypothesis.
His theory is based on his background in marine biology, a discipline in which he holds a doctoral degree. In his studies, he saw how environmental factors created oxidative stress in marine life. Toxins, trauma, and even natural wear and tear would interact with the biological systems in the marine life and cause deterioration.
The same process, he believes, could explain Alzheimer’s and dementia.
People don’t fear Alzheimer’s specifically, he said, as much as they fear the effects of aging. Just like other aspects of physical health that deteriorate with age, “you can do a lot to do reduce your chances of having the disease,” Perry explained. When patients present with Alzheimer’s, he said, many of the cells in their body – not just the brain – show signs of stress.
He recommends reducing the oxidative stress within the body with the tried and true elements of “good, clean living:” lots of fruits and vegetables, exercise, reduced stress, and a reason to live decrease the likelihood of Alzheimer’s by 50%, Perry said.
Cancer
For UTSA researcher Matthew Gdovin, curing cancer is about more than discovering a way to kill cells in a petri dish. In his teaching and research, Gdovin doesn’t consider the work done without taking the treatment “from the lab bench to the patient’s bedside.”
This has led Gdovin on an entrepreneurial venture he never anticipated.
In the lab, Gdovin developed a cancer treatment process that uses targeted light sources and a nanoparticle injected into the body to react to the light. The nanoparticle diffuses into any cell it meets, and then light rays target the cancer cells. The reaction creates an acidic condition that causes the cancer cells to self-destruct.
So far the treatment has been effective in the lab on two forms of triple negative breast cancer, pancreatic cancer, and two forms of prostate cancer, killing 98% of targeted cells within three hours.
“We do not believe that there is a cancer we cannot kill if we can attach the nanoparticles and [expose] them to the light,” Gdovin said. He hopes that this will eventually apply to blood cancers as well.
Success in the lab, however, does not always translate to lives saved.
“It’s very expensive to take any kind of health care products from concept to commercialization,” said Tom Roberts, Gdovin’s business partner with Vitanova Biomedical, a company founded to carry out the clinical trials for Gdovin’s treatments.
When Gdovin approached UTSA about patenting his treatment to move it into clinical trials, university officials encouraged him to found his own company and trained him in the business skills he would need. Vitanova Biomedical had to raise $3.5 million to conduct the preclinical trials to file with the FDA before trials could even begin. Now the company partners with the clinical research organization Cancer Insight, as well as oncology clinics and hospitals as it pursues FDA approval for the treatment.
To Roberts and Gdovin, theoretical treatment has never been good enough.
“There’s a passion that you really have to have,” said Gdovin, who has a doctorate in physiology.
For both men, that passion comes from loved ones affected by cancer. Roberts lost his mother to the disease, and Gdovin’s mother is currently fighting Stage IV breast cancer.
Tularemia
While you might think you’ve never heard of tularemia, you probably have, Karl Klose said. While very few people come down with “rabbit fever” in their natural habitat, in its weaponized form, tularemia is one of the most potent biological weapons on earth, comparable to anthrax and the plague.
“It’s known to be a pretty significant weapon that can cause a lot of sickness and death,” Klose said. “[Anthrax, the plague, and tularemia] are kind of like the three evil brothers at the top of the list of the most dangerous bioweapons.”
Klose, who has a doctorate in microbiology, is the director of the South Texas Center for Emerging Infectious Disease, where groups study various viruses, fungi, parasites, and immune responses. “We’re always looking for the Achilles’ heel of these organisms,” Klose said.
The bacterium that causes tularemia, Francisella tularensis, is one of those organisms. In the rare cases that the disease is contracted from an animal host, it usually cures itself over time with few symptoms. However, if it gets into the lungs, which is how the weaponized aerosol version works, the mortality rate skyrockets to 30%-50%.
“When it gets into the lungs, it is a very, very serious disease,” Klose said.
As early as World War II, Russia and Japan both showed interest in developing the aerosol version of the agent. The U.S. followed suit, and now the technology is more widely available.
“There’s a lot of uncertainty as to bio-threats around the globe. The fact that we don’t have any preventative measures against pulmonary tularemia is pretty unnerving,” Klose said.
Due to the bacterium’s classification as a Category A biological weapon, UTSA’s work on finding a vaccine for pulmonary tularemia happens under close scrutiny from the National Institutes for Health, Centers for Disease Control, FBI, and even local law enforcement. The lab had to prove that it had the capacity to monitor all contact with the samples with closed-circuit television and had to demonstrate the facility’s containment capacity. Once a year, the CDC comes to UTSA and checks the samples.
Klose knows that he’s dealing with a worthy opponent, and that the government’s concern for the samples is well-founded.
“If bacteria can get around the very formidable human immune system, that means they have some very special tricks up their sleeve,” Klose said.
Francisella tularensis and its closest cousins survive by using a knife-like feature to destroy the body’s “Roomba-like” microphages, which isolate and destroy the bacteria. Klose’s vaccine aims to deactivate the knife feature so the body’s immune system can do its work. Crippling instead of killing the disease will actually strengthen the immune system, Klose said, because the immune system will still have to work.
He hopes that by developing a vaccine for pulmonary tularemia, using it as a biological weapon will become pointless. “Once you can prevent a disease, it becomes far less scary,” he said.
The work is challenging, but in a good way, he said. It’s difficult to test something that does not occur frequently in nature, and there’s no way to ethically run a clinical trial that would infect people with the deadly disease. Currently UTSA has the only researchers who have been allowed to test the vaccine on non-human primates, a gold-standard substitute which may be the furthest the trials can go. Once the vaccine has proven effective, it can be modified to treat anthrax and plague. The vaccine will likely always be very expensive and most useful to people at high risk of exposure to biological weapons, such as military populations or possibly even those living in densely populated areas that might be considered high-value targets, like Washington, D.C., or New York City. The disease cannot pass from human to human, so there’s little risk of an epidemic spreading beyond those in immediate contact with the agent.
For those concerned about vaccines in general, Klose can only speak for himself.
“If I can be vaccinated against anything, I am,” he said.
