For more than 15 years, Dr. Claudia Marino has chased a single question: Can we protect the brain from Alzheimer’s disease before it ever takes hold? At UTMB, with the support of philanthropic funding, she may be closer than anyone has ever been.
Deep in the mountainous Antioquia region of Colombia in the 1980s, clinical researchers led by renowned neuroscientist Dr. Francisco Lopera made a remarkable discovery.
A particular family carried a rare genetic mutation that caused a unique, early-onset form of Alzheimer’s disease with near certainty, essentially guaranteeing development of the condition by age 45.
The mutation—known as PSEN1 E280A but referred to by locals as “La Bobera”—was aggressive, early, and practically unavoidable.
For researchers, this was something extraordinarily rare. It was a living population in which the cause of Alzheimer’s was known and predictable. On its own, it was one of the most significant findings in Alzheimer’s research.
Then came an even more unexpected discovery.
Within that same family, a handful of individuals carried the same devastating mutation but showed almost no cognitive decline.
Their brains mirrored the family’s pathological structure, housing the sticky amyloid and tau proteins that destroy neural connections over decades. Yet, these individuals remained cognitively intact well beyond their genetic curfew.
After decades of investigation, researchers in 2019 and 2023 traced that protection to two naturally occurring genetic variants: APOE3 Christchurch (APOE3Ch) and RELN-COLBOS.
Remarkably, these mutations developed in human patients without any laboratory intervention and provided nearly 30 years of cognitive protection against one of the most aggressive forms of Alzheimer’s known to science.
One of the researchers behind these recent discoveries is Dr. Claudia Marino. An assistant professor of neurology at The University of Texas Medical Branch (UTMB), Dr. Marino works at the Sealy Institute for Drug Discovery.
Today, her work at UTMB is guided by one question: How can we protect against Alzheimer’s?
Armed with recent multiyear philanthropic support, the answer she is pursuing has the potential to shift how we think about Alzheimer’s, moving from a disease to be treated to one that might be prevented.
A season of suffering and serendipity
In 2011, Dr. Marino was a master’s student in Italy, searching for a thesis topic. Around the same time, her close friend’s father had just been hospitalized with a severe form of Alzheimer’s disease. It was aggressive and void of adequate treatment options.
Upon witnessing the suffering and stress caused by Alzheimer’s, Dr. Marino set her sights on making a difference in the battle against this destructive disease.
Then, serendipity struck.
“I was hoping I could be involved in research that was supporting this type of work,” Dr. Marino recalls. “And the serendipity was that my thesis mentor offered me the opportunity to test some small molecules designed to help against Alzheimer’s. Since then, I became so passionate that I wanted to stay in this field, because I thought there was a really important need to find therapies.”
That moment of serendipity has sustained Dr. Marino for more than 15 years. Her training moved from biophysical chemistry in Italy to a joint PhD between UTMB and the University of Palermo, investigating the biological properties of protective proteins.
She then conducted a postdoctoral fellowship at Harvard Medical School’s Schepens Eye Research Institute under Dr. Joseph F. Arboleda-Velasquez, an internationally recognized scientist and associate professor of ophthalmology. There, the mission was to convert the protective genetic variants found in Colombian patients into possible therapies.
During this fellowship, Dr. Marino made significant contributions to two landmark findings that identified APOE3Ch and RELN-COLBOS as naturally occurring genetic variants capable of protecting the brain against Alzheimer’s.
She now leads her own laboratory at UTMB, weaving together every thread of training and personal experience into an ambitious research program.
More than memory loss
For most people, Alzheimer’s disease means memory loss. For Dr. Marino, that statement is true but incomplete.
“Memory loss or dementia is really the very final phase of a disease that started about 20 years earlier,” she explains.
Inside the brain, specific proteins (amyloid and tau) become altered. This causes them to grow sticky and group into deposits that attack neurons and disrupt the synaptic connections that allow us to not just remember, but also think, speak, and function.
By the time a patient walks into a clinic with reports of memory problems, the damage has often been accumulating for decades.
“Most of the time, it’s already too late. All the damage is there,” she says. “And on the other side, we are still facing the challenge of targeting the proper cause. That’s why it’s so complex.”
The current treatment landscape conveys that complexity. Most FDA-approved interventions address symptoms rather than the underlying disease process.
A handful of newer antibody therapies show modest effects on some of the disease’s causes, which is encouraging. But not all patients are eligible due to the risk of serious side effects.
After more than 120 years since Alzheimer’s was first described in 1906, there is still no cure.
“We simply act too late,” Dr. Marino says plainly. “And the therapies don't always work, and the effects are not always very strong. We need more.”
A new path to the brain
What Dr. Marino is building at UTMB is a system for delivering the same protective genetic variants found in those Colombian patients directly to brain cells in people with Alzheimer’s.
The challenge, however, is not just identifying the right genes but getting them where they need to go.
The brain is separated from the rest of the body by the blood-brain barrier. This protective mechanism keeps harmful substances out of the brain but also blocks most therapeutic agents from reaching the neurons that need them.
Standard gene therapy approaches use viral delivery systems that carry significant risks and limitations, including size constraints and the potential for immune responses.
Dr. Marino is working with a novel technology called the mini-nucleosome. This patented non-viral delivery cargo, developed by AAVINUE Inc., can effectively carry genetic material across the blood-brain barrier, with early evidence of strong stability and no observed toxicity in animal models.
Unlike viral approaches, there is no size limit on what it can carry. And unlike monthly injection regimens, preliminary data suggests it remains stable for more than a year.
“It’s a delivery of a gene, and it’s known as less risky than the current gene therapy approaches,” she explains. “It can reach the brain, which is another important limitation of curing brain diseases, and it’s stable.”
“Almost like a vaccine, patients would no longer be as susceptible.”
Dr. Sanja Sever, professor and vice president of drug discovery at UTMB, sees the same potential.
“Dr. Marino’s investigation will not only advance fundamental knowledge but also has significant potential to redefine how we approach therapeutic options for neurodegenerative diseases.”
Dr. Agenor Limon, associate professor of neurology and director of UTMB’s Mitchell Center for Neurodegenerative Diseases, expands on the significance of this project.
“What makes Dr. Marino’s research especially exciting,” he says, “is its translational potential. Her work aims to leverage these naturally protective pathways to develop therapeutic strategies that could mimic or enhance these resilience mechanisms in individuals vulnerable to Alzheimer’s disease.”
“This approach could open entirely new avenues for precision therapeutics in neurodegenerative disease.”
The goal is not merely treatment but protection. If the mini-nucleosome can successfully deliver the protective genetic variants to brain cells, and if those variants offer the same protection observed in Colombian patients, the result would work more like a vaccine than a conventional therapy.
Patients would receive the genetic material and, in theory, become significantly less susceptible to the disease process that eventually leads to dementia.
The disease on a dish
One of the most significant advances in Dr. Marino’s research pipeline is the use of patient-derived induced pluripotent stem cells (iPSCs)—made possible at UTMB through the support of the Moody Brain Health Institute. This is a technology that has only recently matured enough to make this kind of research possible.
From skin or blood cells donated by patients, researchers can reprogram those cells into any cell type needed for study, including neurons and the supporting cells of the brain.
The result is neurons that carry the full genetic and biological history of the patient who donated them, including the factors that may be contributing to their Alzheimer’s pathology, without the need for invasive brain biopsies.
“We can recreate, on a dish, cells that have a patient’s history,” Dr. Marino explains. “If a patient is diagnosed with Alzheimer’s, we can have all of those genetic factors on a dish and ask whether our delivery system can successfully rescue those phenotypes.”
This system runs in parallel with animal models, allowing researchers to study how a therapy distributes through the body and reaches the brain. The combination provides a more robust picture of whether the mini-nucleosome system is working and what areas need to be optimized before clinical trials can become a realistic next step.
The bridge philanthropy builds
Dr. Marino began her independent career as a principal investigator at UTMB just one and a half years ago. She is building her laboratory, her team, and her research pipeline at the same time. This phase of a scientific career is one that requires exactly the kind of flexible, risk-tolerant investment that federal funding rarely provides.
Multiyear philanthropic support from the JSRM Foundation has made this project possible, and for Dr. Marino, the significance extends beyond the resources.
“This was, honestly, a dream come true,” she says. “I’m a junior investigator, so I really benefit from support for high-risk, high-reward projects. I am very grateful that a foundation of philanthropic support really supports my research.”
“Federal funding requires very strong data and very solid foundations. Philanthropic support is allowing me to bridge that gap.”
Federal grants are essential for scientific research, but they usually require strong existing evidence, a proven track record, and proposals that closely follow established funding requirements.
Philanthropic support operates differently. It can take a chance on a hypothesis that is theoretically strong but experimentally early. It can back a scientist who has the training and vision but not yet the publication record that would make them immediately competitive for a major federal award.
“Philanthropic support is allowing me to obtain all of the necessary data and experimental outcomes that can give a much more solid foundation of the overall research mission,” she explained. “And then, of course, it will allow me to make a stronger proposal that can be submitted to federal funding.”
In this way, philanthropy is a bridge, as she calls it, between a promising idea and the institutional support required to make it a clinical reality.
A world without Alzheimer’s
When asked to describe a future without Alzheimer’s, Dr. Marino does not reach for science—though, she would gladly discuss it. Instead, she reaches for the family.
“Alzheimer’s disease is not just the pathology of the individual with Alzheimer’s,” she says. “It’s the pathology of the individual and the family supporting them.”
She thinks about what it means to lose the ability to speak, eat, or recognize the people you love. She thinks about the caregivers—the estimated 13 million Americans who provided more than 19 billion hours of unpaid care in 2025 alone. She thinks about the infrastructure required to sustain it all.
“A future with no Alzheimer’s,” she adds, “can really give, in the long term, a better life, in a more global way.”
She points to the progress medicine has already made with other diseases that once seemed insurmountable, such as cancer or hypertension. These conditions, while serious, are now manageable in ways they were not a generation ago.
“I’m very optimistic,” she says. “We have better tools and understanding now. There is also all this emerging technology that really helps, and there are pipelines of clinical trials trying to test from every different angle. This allows us to get one step closer every day.”
The research question Dr. Marino has carried since 2011 is as clear today as it has ever been.
“Can we protect against Alzheimer’s?” she says eagerly. “That’s the big question. And that’s what I’m still trying to answer.”
Dr. Marino’s work is one part of a larger story. At UTMB, researchers, clinicians, and educators across disciplines are working every day to understand, prevent, and treat brain diseases. The UTMB Brain Health Fund supports all of it—from early-stage discovery to patient care to the next generation of scientists who will carry this work forward.