Category: 8. Health

Precision cancer treatment on a larger scale is moving closer after researchers have developed an AI platform that can tailor protein components and arm the patient’s immune cells to fight cancer. The new method, published in the scientific journal Science, demonstrates for the first time, that it is possible to design proteins in the computer for redirecting immune cells to target cancer cells through pMHC molecules.

This dramatically shortens the process of finding effective molecules for cancer treatment from years to a few weeks.

We are essentially creating a new set of eyes for the immune system. Current methods for individual cancer treatment are based on finding so-called T-cell receptors in the immune system of a patient or donor that can be used for treatment. This is a very time-consuming and challenging process. Our platform designs molecular keys to target cancer cells using the AI platform, and it does so at incredible speed, so that a new lead molecule can be ready within 4-6 weeks.”

Timothy P. Jenkins, Associate Professor at the Technical University of Denmark (DTU) and last author of the study

Targeted missiles against cancer

The AI platform, developed by a team from DTU and the American Scripps Research Institute, aims to solve a major challenge in cancer immunotherapy by demonstrating how scientists can generate target treatments for tumor cells and avoid damaging healthy tissue.

Normally, T cells naturally identify cancer cells by recognizing specific protein fragments, known as peptides, presented on the cell surface by molecules called pMHCs.It is a slow and challenging process to utilise this knowledge for therapy, often because the variation in the body’s own T-cell receptors makes it challenging to create a personalised treatment. 

Boosting the body’s immune system

In the study, the researchers tested the strength of the AI platform on a well-known cancer target, NY-ESO-1, which is found in a wide range of cancers. The team succeeded in designing a minibinder that bound tightly to the NY-ESO-1 pMHC molecules. When the designed protein was inserted into T cells, it created a unique new cell product named ‘IMPAC-T’ cells by the researchers, which effectively guided the T cells to kill cancer cells in laboratory experiments.

“It was incredibly exciting to take these minibinders, which were created entirely on a computer, and see them work so effectively in the laboratory,” says postdoc Kristoffer Haurum Johansen, co-author of the study and researcher at DTU.

The researchers also applied the pipeline to design binders for a cancer target identified in a metastatic melanoma patient, successfully generating binders for this target as well. This documented that the method also can be used for tailored immunotherapy against novel cancer targets.

Screening of treatments

A crucial step in the researchers’ innovation was the development of a ‘virtual safety check’. The team used AI to screen their designed minibinders and assess them in relation to pMHC molecules found on healthy cells. This method enabled them to filter out minibinders that could cause dangerous side effects before any experiments were carried out.

“Precision in cancer treatment is crucial. By predicting and ruling out cross-reactions already in the design phase, we were able to reduce the risk associated with the designed proteins and increase the likelihood of designing a safe and effective therapy,” says DTU professor and co-author of the study Sine Reker Hadrup.

Five years to treatment

Timothy Patrick Jenkins expects that it will take up to five years before the new method is ready for initial clinical trials in humans. Once the method is ready, the treatment process will resemble current cancer treatments using genetically modified T cells, known as CAR-T cells, which are currently used to treat lymphoma and leukaemia.Patients will first have blood drawn at the hospital, similar to a routine blood test. Their immune cells will then be extracted from this blood sample and modified in the laboratory to carry the AI-designed minibinders. These enhanced immune cells are returned to the patient, where they act like targeted missiles, precisely finding and eliminating cancer cells in the body.

New research from investigators at Mass General Brigham suggests that a commonly used type 2 diabetes medication is linked to a higher rate of heart-related conditions compared to medications that hit other targets. The study examined nationwide data from nearly 50,000 patients treated with different sulfonylureas and found that glipizide – the most widely used drug in the U.S. within this category – was linked to higher incidence of heart failure, related hospitalization and death compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Results are published inJAMA Network Open.

Patients with type 2 diabetes are at heightened risk of adverse cardiovascular incidents such as stroke and cardiac arrest. While sulfonylureas are popular and affordable diabetes medications, there is a lack of long-term clinical data on how they affect cardiac health in comparison to more neutral alternatives like dipeptidyl peptidase 4 inhibitors.”

Alexander Turchin, MD, MS, corresponding author of the Division of Endocrinology at Brigham and Women’s Hospital (BWH)

Turchin and co-authors emulated a target trial by analyzing electronic health records and insurance claims data from the BESTMED consortium. The cohort included 48,165 patients with type 2 diabetes and moderate cardiovascular risk who received care at 10 different study sites across the country, including BWH, as well as those covered by two different national health insurance plans.

The researchers studied the five-year risk of major adverse cardiovascular events in patients treated with different sulfonylureas (glimepiride, glipizide or glyburide) or DPP4i in addition to metformin, a primary diabetes medication. They found that glipizide was associated with a 13% increase in cardiovascular risk when compared to DPP4i, while glimepiride and glyburide led to relatively smaller and less clear effects, respectively. The authors propose that further research is needed to uncover the underlying mechanisms.

“Our study underscores the importance of evaluating each drug in a particular pharmacological class on its own merits,” said Turchin.

Cancer cells and tumors do not exist in a vacuum. Far from the isolation and self-sufficiency of the fictional Wakanda, tumors develop in and alter the nearby milieu of immune cells, connective tissue, blood vessels and a sea of proteins and carbohydrates that provide structure and other supportive functions.

Cancer cells interact with this neighborhood – which scientists term the tumor microenvironment – in many ways, including obtaining extra resources needed to fuel their unchecked growth. Like a fishing trawler deploying its net, pancreatic ductal adenocarcinoma (PDAC) cells reform their cell surfaces to grab additional nutrients from the jelly-like substance between cells called the extracellular matrix.

This cellular scavenging process – known as macropinocytosis – affects the area surrounding the tumor, making the connective tissue stiffer and preventing immune cells from reaching the tumor.

Scientists at the NCI-Designated Cancer Center at Sanford Burnham Prebys published findings July 24, 2025, in Cancer Cell demonstrating that blocking macropinocytosis reshapes the tumor microenvironment to be less fibrous and to allow more access to immune cells. These changes made immunotherapy and chemotherapy more effective in treating PDAC tumors in mice.

The researchers started by observing cells in the tumor microenvironment called fibroblasts that typically form connective tissue and produce many components of the extracellular matrix that are captured during macropinocytosis. In the presence of a tumor, some nearby fibroblasts are coerced to become cancer-associated fibroblasts (CAF) that help tumors grow.

These CAFs are among the cells surrounding the tumor, and they will support tumor growth by providing metabolites and growth signals, as well as helping in other ways.”

Yijuan Zhang, PhD, staff scientist at Sanford Burnham Prebys and lead author of the study

The scientists found that blocking macropinocytosis exacerbated the metabolic stress experienced by CAFs that are deprived of glutamine, one of the 20 amino acids used to build proteins throughout the body. Because PDAC relies upon glutamine much more than other cancers, CAFs in the pancreatic cancer tumor microenvironment are routinely starved of glutamine. After preventing pancreatic CAFs from using the same scrounging strategy as PDAC tumors, the scientists observed a change to a different subtype of CAF marked by the expression of genes that promote inflammation.

“Most pancreatic CAFs are myofibroblasts that promote stiffness and density in the tumor microenvironment and make it more difficult for immune cells and drugs to reach the tumor,” said Cosimo Commisso, PhD, senior author and interim director and deputy director of the institute’s cancer center. “Our experiments led to a subtype reprogramming with fewer myofibroblasts and more inflammatory CAFs, and we wondered how this change would affect the overall tumor microenvironment.”

The research team found that significant changes in the tumor neighborhood resulted from preventing macropinocytosis in CAFs.

“There were fewer deposits of collagen that make the tumor microenvironment stiff or fibrotic, more access for CD4+ and CD8+ T cells to infiltrate the tumor, and vascular expansion, which means a widening of blood vessels that can promote drug delivery,” said Zhang.

The investigators then wanted to see how these tumor microenvironment modifications might make a difference for patients with PDAC and other cancers that rely on macropinocytosis for fuel. They tested the effects of combining a treatment to block macropinocytosis with immunotherapy and chemotherapy.

“Infiltrating T cells are rich in a cell surface protein called PD-1 that dampens the immune response, so we combined a macropinocytosis inhibitor called EIPA with an anti-PD-1 antibody,” said Commisso. “We found it significantly suppressed tumor metastasis and prolonged mouse survival.”

“Our findings were similar when using EIPA as a pre-treatment before using the chemotherapy gemcitabine,” said Zhang. “In addition to synergistically suppressing tumor growth in mice with PDAC, it also reduced the spread of micrometastases in the lungs.”

The scientists will continue to explore how to prevent tumors from scavenging energy to reshape the tumor microenvironment into one that makes cancer treatments more effective.

“We believe this is a very promising strategy to pursue for developing combination therapies for cancer patients,” said Commisso. “Especially for pancreatic cancer that is the third leading causes of cancer deaths despite accounting for only three percent of cases.”

A new study published in The Lancet Diabetes & Endocrinology reveals that most children and young adults diagnosed with type 1 diabetes (T1D) in sub-Saharan Africa may actually have a form of diabetes that is not autoimmune in origin. These findings could influence diagnostic and treatment approaches in the region and have broader implications for diabetes care globally.^1,2

“This is the first study across several Sub-Saharan African countries to use the same lab tests and genetic tools to learn more about type 1 diabetes. We’ve done similar research in the United States. with different groups, but what’s exciting here is being able to compare results between Africa and the United States,” said Dana Dabelea, MD, PhD, distinguished professor and associate dean of research at the Colorado School of Public Health on the University of Colorado Anschutz Medical Campus, and a co-author of the study.

The cross-sectional study enrolled 894 participants with youth-onset, insulin-treated diabetes from Cameroon, Uganda, and South Africa. All participants were of self-reported Black African ethnicity, diagnosed before the age of 30 years, and had a body mass index under 30 kg/m². Investigators assessed autoimmunity using islet autoantibody testing (GADA, IA-2A, and ZnT8A) and evaluated genetic predisposition through a type 1 diabetes genetic risk score (GRS).

Among the participants, only 312 (34.9%) tested positive for one or more islet autoantibodies. This group exhibited features typical of autoimmune T1D, including severe insulin deficiency—225 of 272 (82.7%) had C-peptide levels below 200 pmol/L—and a high GRS for T1D. The remaining 582 participants (65.1%) were autoantibody-negative and showed significantly lower T1D GRS compared with autoantibody-positive individuals (median 9.66 vs 11.76; P<.0001). Despite the lack of autoimmune markers, most of this group also had severe insulin deficiency, suggesting a distinct form of non-autoimmune diabetes.

“This suggests that many young people in this region have a different form of T1D altogether and is not autoimmune in origin,” said Dabelea.

To contextualize these findings, the researchers compared data from their African cohort with participants in the U.S.-based SEARCH for Diabetes in Youth study. In SEARCH, a similar non-autoimmune diabetes pattern—autoantibody negativity and low GRS—was found in 15.1% of Black participants with youth-onset diabetes. In contrast, White participants in SEARCH who were autoantibody-negative still demonstrated high genetic susceptibility to T1D, indicating that their disease remained autoimmune in nature.

“The identification of this T1D diabetes subtype in Sub-Saharan African populations and among individuals of African ancestry in the U.S. suggests a potential ancestral or genetic link,” Dabelea said. “These findings highlight the need to consider alternative etiologies in this group, and a deeper understanding of the underlying mechanisms may provide important insights for future prevention and treatment strategies.”

The authors noted that while these autoantibody-negative cases in Africa do not appear consistent with type 2 diabetes or malnutrition-associated diabetes, their pathogenesis remains unclear. These individuals were not obese, had early-onset disease, and lacked the genetic features of type 2 diabetes. The study ruled out malnutrition-associated diabetes based on similar rates of rural residence, sex, and height across groups.

“This novel, non-autoimmune diabetes subtype observed in participants from these sub-Saharan African countries was usually accompanied by severe insulin deficiency and was not associated with the clinical or genetic features of type 2 diabetes,” the authors wrote.

The findings suggest that traditional markers used to diagnose T1D in high-income countries may not be sufficient in African populations, and that clinicians should consider alternative causes of insulin-deficient diabetes when evaluating young patients.

The study was supported by the UK National Institute for Health and Care Research and used standardized laboratory methods and population-specific autoantibody thresholds to ensure data accuracy. The authors emphasized the importance of further research into environmental and genetic factors that may underlie this atypical diabetes subtype.

References:

1. University of Colorado Anschutz Medical Campus. A new diabetes subtype identified in Sub-Saharan Africa and Black Americans, study finds. EurekAlert. July 21, 2025. Accessed July 24, 2025. https://www.eurekalert.org/news-releases/1091946
2. Katte JC, Squires S, Dehayem MY, et al. Non-autoimmune, insulin-deficient diabetes in children and young adults in Africa: evidence from the Young-Onset Diabetes in sub-Saharan Africa (YODA) cross-sectional study. The Lancet Diabetes & Endocrinology. Published online July 21, 2025. doi:https://doi.org/10.1016/S2213-8587(25)00120-2

Salk Institute Professor Diana Hargreaves was named a 2025 All-Star Translational Award Program grantee by the V Foundation for Cancer Research. The award comes as a recognition of Hargreaves’ exceptional success with her previous V Foundation grant in 2016, which aimed to identify better drug targets for cancers with mutations in a multi-protein complex called SWI/SNF that regulates DNA structure and stability. She and her collaborator, Gregory Botta, an associate professor at UC San Diego Moores Cancer Center, will receive $1 million to advance her new project to improve immunotherapy-a treatment that utilizes the body’s own immune cells to fight cancer-in patients with pancreatic cancer.

Diana is a true innovator in the field of cancer research, and this second award from the V Foundation is a testament to her continued scientific excellence. We enthusiastically support her efforts to translate the fundamental discoveries she has made regarding immune checkpoint blockade to the treatment of pancreatic cancer, which thus far has been challenging to address with immunotherapy.”

Gerald Joyce, Salk President

The V Foundation was founded by ESPN and national basketball champion and coach Jim Valvano to fund “game-changing” cancer research grants in North America. The foundation’s competitive selection process identifies scientists like Hargreaves who are using cutting-edge approaches to tackle cancer in innovative ways.

V Foundation All-Star awards reinvest in previous grant recipients. Hargreaves’ first V Foundation project in 2016 aimed to find new strategies for treating epithelial ovarian cancers with mutations in ARID1A, a protein in the SWI/SNF complex. Her new project, titled “Preclinical and Clinical Studies of Immune Checkpoint Inhibitor Therapy in SWI/SNF Altered or Inhibited Pancreatic Cancer,” explores the role of this same protein complex in pancreatic cancer.

Pancreatic cancer is set to become the second leading cause of cancer-related deaths in the United States by 2030. Due to its high mortality rate-roughly 90% of patients-the need to develop effective therapies for pancreatic cancer is urgent. Immunotherapies such as immune checkpoint inhibitors have revolutionized cancer care for other cancer types but have been generally ineffective in the pancreas-except, notably, in patients with SWI/SNF mutations, for whom Botta found that immunotherapy is far more effective.

Already, Hargreaves’ discoveries have revealed that ARID1A mutations make immunotherapy more effective for people with difficult-to-treat cancers. Hargreaves will now investigate whether the immunotherapy-boosting effect of mutated ARID1A extends to SWI/SNF mutations more generally, as well as test whether SWI/SNF-blocking drugs could improve clinical outcomes for the 85-90% of patients with unmutated SWI/SNF tumors. In parallel, Botta will run an investigator-initiated trial of combination immunotherapy and chemotherapy for metastatic pancreatic cancer patients with SWI/SNF mutations. Collectively, these studies could help define biomarkers for immunotherapy in pancreatic cancer and boost patient survival.

These studies build upon a collaborative grant awarded to Botta and Hargreaves through Curebound. Hargreaves was named the American Cancer Society’s Early-Career Researcher of the Year in 2024 and a Pew-Stewart Scholar for Cancer Research in 2019. She is also a leader in Salk’s new Neuroimmunology Initiative.

DALLAS – July 24, 2025 – Researchers at UT Southwestern Medical Center have discovered how a hormone interacts with a receptor on the surface of immune cells to shield cancer cells from the body’s natural defenses. The findings, published in Nature Immunology, could lead to new immunotherapy approaches for treating cancer as well as potential treatments for inflammatory disorders and neurologic diseases.

“Myeloid cells are among the first group of immune cells recruited to tumors, but very quickly these tumor-fighting cells turn into tumor-supporting cells. Our study suggests that receptors on these myeloid cells get stimulated by this hormone and end up suppressing the immune system,” said Cheng Cheng “Alec” Zhang, Ph.D., Professor of Physiology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Zhang co-led the study with first author Xing Yang, Ph.D., a postdoctoral researcher in the Zhang Lab.

Current immunotherapies, such as immune checkpoint inhibitors, are effective for only about 20%-30% of cancer patients, Dr. Zhang said, suggesting that there are multiple ways that cancers evade attack from the immune system.

Several years ago, researchers in the Zhang Lab studying cancer-fighting immune cells called myeloid cells identified an inhibitory receptor called LILRB4. Stimulating this receptor blocked the myeloid cells’ ability to attack tumors.

Dr. Zhang, Dr. Yang, and their colleagues then did a genome-wide screen of all proteins that might interact with LILRB4. A promising hit was a hormone called SCG2. Although researchers have suggested that SCG2 plays a role in immune response, its function and receptor were unknown. Laboratory experiments confirmed that SCG2 binds to LILRB4, kicking off a signaling cascade that turned off the cancer-fighting abilities of myeloid cells and inhibited their ability to recruit cancer-fighting T cells to tumors.

In mice genetically altered to express the human form of LILRB4, injected cancer cells that produced SCG2 grew rapidly as tumors. Treating these mice with an antibody that blocks LILRB4 significantly slowed cancer growth, as did artificially ridding the animals’ bodies of SCG2.

Together, these experiments suggest that interactions between LILRB4 and SCG2 allow cancer to grow unchecked by myeloid cells, T cells, and potentially other immune cell types. Dr. Zhang suggested that disrupting this interaction could someday offer a new immunotherapy option to treat cancer. Conversely, because this interaction neutralizes myeloid cells’ immune activity, delivering extra SCG2 could be a promising treatment for autoimmune or inflammatory disorders spurred by myeloid cells. Dr. Zhang and his colleagues plan to investigate both ideas in future studies.

Other UTSW researchers who contributed to this study include Xuewu Zhang, Ph.D., Professor of Pharmacology and Biophysics; Cheryl Lewis, Ph.D., Associate Professor in the Simmons Cancer Center and of Pathology; Lin Xu, Ph.D., Assistant Professor in the Peter O’Donnell Jr. School of Public Health and of Pediatrics; Jingjing Xie, Ph.D., Instructor of Physiology; Qi Lou, Ph.D., Assistant Instructor of Physiology; Lei Guo, Ph.D., Computational Biologist; and Meng Fang, Ph.D., Chengcheng Zhang, Ph.D., Ankit Gupta, Ph.D., and Lianqi Chen, Ph.D., postdoctoral researchers.

Dr. Alec Zhang holds the Hortense L. and Morton H. Sanger Professorship in Oncology and is a Michael L. Rosenberg Scholar in Medical Research. Dr. Xuewu Zhang and Dr. Xu are members of the Simmons Cancer Center.

This study was funded by grants from the National Cancer Institute (NCI) (R01CA248736, R01CA263079, and Lung Cancer 779 SPORE Development Research Program), the Cancer Prevention and Research Institute of Texas (RP220032, RP15150551, RP190561), The Welch Foundation (AU-0042-20030616, I-1702), Immune-Onc Therapeutics Inc. (Sponsored Research Grant No. 111077), the National Institutes of Health (R35GM130289), and NCI Cancer Center Support Grant (P30CA142543).

The University of Texas has a financial interest in Immune-Onc in the form of equity and licensing. Dr. Alec Zhang holds equity in and had sponsored research agreements with Immune-Onc.

About UT Southwestern Medical Center 

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 24 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.

Although the number of human infections with H5N1 avian flu rose last year, along with outbreaks in dairy cows and poultry, the illnesses were mostly mild, raising the possibility that immunity from seasonal flu virus infection might play a role. Now, new evidence from ferret experiments suggests that earlier exposure to the 2009 H1N1 seasonal flu virus may provide some immunity.

Over the past few decades, human infections with H5N1 have been known for serious illness and high case-fatality rates. However, of 70 cases reported in the United States since 2024, only one was fatal, raising questions about why the 2.3.4.4b clade, which has circulated globally since 2020 and includes the B3.13 subtype circulating in dairy cattle, has a lower disease severity profile. 

In the early months of H5N1 circulation in dairy cattle and as reports of mostly mild human H5N1 infections, primarily in farm workers, mounted in the United States, federal health officials announced a plan to produce 4.8 million doses of H5N1 vaccine for pandemic preparedness. However, with the change in presidential administration this year, the vaccine plan is in limbo, given that the Department of Health and Human Services cancelled Moderna’s $590 million award for late-stage development of a candidate H5 avian flu vaccine and the development of other prepandemic vaccines. 

To explore the potential benefit from seasonal flu antibodies, a research team from Pennsylvania State University and the University of Pennsylvania conducted a series of experiments in ferrets, which are considered the best animal model for flu in humans, given similar clinical symptoms and transmission dynamics. The team published its findings yesterday in Science Translational Medicine.

Experiments sort out immunity, test transmission

In experiments conducted in a biosafety level 3 facility, the researchers studied ferrets that had antibodies to seasonal flu viruses—including H1N1, H3N2, and influenza B—and a control group of ferrets with no immunity to flu viruses.

In one set of experiments, they exposed the animals through the internasal route to the H5N1 virus that was linked to outbreaks on mink farms in Spain in 2022. Ferrets without flu immunity and those with immunity only to influenza B lost weight and had severe illness. Those that had been exposed to H3N2 lost some body weight but survived. Meanwhile, ferrets exposed to H1N1 didn’t lose any weight and all survived.

In the next round of testing, the team infected the ferrets with the US dairy cattle virus to gauge immunity from earlier seasonal flu virus antibodies. This time, they didn’t inoculate the animals with H5N1 intranasally. Instead, they exposed them to ferrets that were already infected with H5N1, which allowed them to examine transmissibility as well as preexisting immunity.

Ferrets without any earlier flu exposure quickly became severely ill or died. Those with earlier immunity to H3N2 got sick and lost weight, with replicating H5N1 virus detected in their noses. Meanwhile, only half of the ferrets with H1N1 antibodies became ill and had very low levels of replicating H5N1 virus in their noses. 

Some reassurance, though ongoing changes and threats remain

In a Penn State news release, lead author Troy Sutton, PhD, associate professor of veterinary and biomedical sciences at Penn State, said the findings demonstrate that preexisting immunity to 2009 H1N1 or H3N2 reduces disease severity, with H1N1 providing even greater protection than H3N2. “This study provides a potential explanation for the mostly mild disease we are seeing in humans, as humans already have immunity to H1N1,” he added.

However, he warned that as H5N1 continues to circulate in animals, it has opportunities to become more lethal. 

Apart from 2.3.4.4b, different H5N1 clades are still infecting people in other parts of the world, including Cambodia, where a spike in human H5N1 illnesses, many severe or fatal, has been fueled by a reassortant (2.3.2.1e) between an older H5N1 clade that has circulated in the country since 2014 and the newer clade 2.3.4.4b virus that is circulating globally. Also, India and Bangladesh continue to report sporadic human infections from the older 2.3.2.1a clade known to circulate in birds and poultry in the region. 

Mathematics may not be the first thing people associate with Alzheimer’s disease research. But for Pedro Maia, an assistant professor of mathematics and data science at The University of Texas at Arlington, analyzing how different parts of the brain interact like a network is revealing new insights into one of the world’s most devastating brain disorders.

Dr. Maia’s latest breakthrough-developed in collaboration with colleagues at the University of California–San Francisco’s Raj Lab-uses advanced mathematical modeling to help explain why Alzheimer’s disease spreads unevenly through the brain. Their work reveals why certain brain regions are more vulnerable to damage from tau, a protein that accumulates in brain cells and disrupts their normal function, while other areas remain more resilient.

The study was recently published in Brain, a leading journal in clinical neurology.

What’s interesting, is how mathematics, data methods and data science, and mathematical modeling can actually bring some advanced insights into Alzheimer’s disease.”

Dr. Pedro Maia, assistant professor of mathematics and data science, The University of Texas at Arlington

Maia and his UCSF colleagues created a mathematical tool-called an extended network diffusion model-that tracks how tau protein builds up and spreads through the brain’s network of interconnected regions. Using this model, researchers can classify genes into four categories: those that follow the brain’s network patterns and increase vulnerability; those that follow the patterns and provide protection; those that act independently but raise risk; and those that act independently and help protect the brain.

It’s a significant step in advancing Alzheimer’s research, helping to answer a question that has baffled researchers for years: Why do some brain regions deteriorate rapidly while others remain largely intact?

The model, as Maia said, “helps us untangle what was previously just a messy bag of genes.”

“The idea is that the brain isn’t uniform-different regions are made up of different kinds of cells and genes, and they’re connected differently too,” he continued. “Regions that are more connected or closer to affected areas are more vulnerable. Isolated regions tend to be more resilient.”

The study used data from 196 people. Of those participants, 102 had been diagnosed with early-stage mild cognitive impairment, 47 with late-stage mild impairment and 47 with Alzheimer’s disease. Previous research by Maia and his colleagues relied on more controlled studies using rodent models.

“Human data, even though it is more challenging to work with given the variables involved, gives us direct insight into how Alzheimer’s progresses in real people,” Maia said. “If we want to develop treatments that work in humans, we need data that comes from humans.”

In Texas, nearly half a million people live with Alzheimer’s disease as the state ranks fourth in the nation for Alzheimer’s cases and second in Alzheimer’s-related deaths. That results in an estimated $24 billion expense for the state annually, according to the Texas Department of State Health Services.

For Maia, applying his mathematics background to Alzheimer’s research has been especially rewarding. He sees it as part of a broader shift in how the field of mathematics is evolving.

“In the past century, physics was the big inspiration for mathematical research,” he said. “Today, biology-especially the brain-is becoming the big source of inspiration. If you’re willing to chat in multidisciplinary settings, you’ll see that math modeling still has a big role to play.”