Dasatanib & Quercetin: New Hope for Diabetic Kidney Disease & ‘Zombie Cells’

A new combination therapy—using the cancer drug dasatanib alongside the naturally occurring compound quercetin—shows promise in reducing inflammation and improving kidney function in preclinical models of diabetic kidney disease. The findings, published in eBioMedicine, offer a potential new avenue for tackling a condition affecting millions and currently lacking a cure.

Diabetic kidney disease impacts over 12 million people in the United States, and stands as the leading cause of kidney failure. Even as existing treatments can sluggish the progression of kidney dysfunction, they don’t address the underlying disease process. Researchers at the Mayo Clinic are now focusing on senescent cells – often called “zombie cells” – as a key target in combating this chronic illness.

What are Senescent Cells and Why Do They Matter?

Senescent cells are cells that have stopped dividing but haven’t died. Instead, they linger in tissues, releasing harmful substances that contribute to inflammation and age-related diseases. These cells accumulate in the kidneys of people with diabetes, exacerbating kidney damage. The approach explored by Mayo Clinic researchers centers on “senolytics”—substances designed to selectively eliminate these lingering, problematic cells.

LaTonya Hickson, MD, the principal investigator of the study and a nephrologist at Mayo Clinic, explained that their research demonstrated the combination therapy reduced the number of senescent cells in a preclinical model of diabetic kidney disease and, importantly, improved kidney function. “Our study found that the combination therapy, given over a short period of time, reduced the abundance of senescent cells…and also improved kidney function,” Dr. Hickson stated.

Building on Previous Findings: A Pilot Clinical Trial

This latest research builds upon a previous pilot clinical trial conducted by Dr. Hickson and her team. That earlier study revealed that the dasatanib-quercetin combination successfully reduced senescent cells in skin and fat tissues of patients with diabetic kidney disease. However, the effect of this therapy specifically on the kidneys themselves hadn’t been fully investigated until now.

Xiaohui Bian, M.D., Ph.D., a nephrologist and lead author of the current study, emphasized the importance of demonstrating a direct effect on the kidneys without resorting to invasive procedures. “It was important to prove that this one-time, short-course treatment has an effect on the kidneys, and we wanted to do so without invasive procedures in patients,” Dr. Bian said.

How the Therapy Works: Preclinical and Cellular Results

The research team utilized a preclinical model of diabetic kidney disease to assess the impact of the combination therapy. They observed improvements in kidney function and an increase in protective factors, alongside a reduction in kidney injury, senescent cells, and inflammation. Further experiments conducted on cultured human kidney cells confirmed these findings, showing a decrease in both senescent cell abundance and the inflammatory processes they trigger.

Quercetin is a flavonoid found in many fruits and vegetables, including onions, apples, and berries. The National Health Service (NHS) notes that it’s an antioxidant with potential anti-inflammatory properties, though more research is needed to fully understand its benefits. Dasatanib, is a tyrosine kinase inhibitor typically used in the treatment of certain types of leukemia. Its ability to target senescent cells is a more recent discovery.

What Does This Signify for Patients?

The results suggest that this combination treatment has the potential to reduce and halt kidney damage caused by diabetes. However, it’s crucial to understand that this research is still in its early stages. The study was conducted in preclinical models and cell cultures, meaning the findings need to be replicated in larger-scale clinical trials involving human patients before any definitive conclusions can be drawn.

It’s also important to note that the study focused on a short-course treatment. The long-term effects of this therapy, as well as potential side effects, remain unknown. The researchers emphasize that this is not a cure, but a promising step towards developing more effective treatments for diabetic kidney disease.

Understanding the Study Design and Limitations

The study published in eBioMedicine utilized a murine model of diabetic kidney disease, meaning the experiments were conducted on mice. While animal models are valuable for initial research, they don’t always perfectly replicate the complexities of human disease. The researchers acknowledge this limitation and stress the need for further investigation in human subjects. The study also focused on specific endpoints – kidney function, inflammation markers, and senescent cell counts – and didn’t assess other potential outcomes.

The research team used a combination of dasatanib and quercetin, administered over a short period. The specific dosage and duration of treatment were determined based on previous studies and preclinical data. Further research is needed to optimize the treatment regimen for human patients.

The Path Forward: Larger Trials and Continued Research

Dr. Hickson believes these promising findings warrant larger-scale studies using senolytics in patients to improve kidney health. “Promising findings from these two investigations now suggest that larger scale studies using senolytics should be pursued in patients to improve kidney health.”

The next steps involve conducting clinical trials to evaluate the safety and efficacy of the dasatanib-quercetin combination in human patients with diabetic kidney disease. These trials will need to carefully assess the potential benefits and risks of the therapy, as well as determine the optimal dosage and duration of treatment. Researchers will also be investigating other potential senolytic drugs and combinations to further refine this therapeutic approach. News-Medical.net reports that the study was published with DOI: 10.1016/j.ebiom.2026.106124.

Individuals with diabetic kidney disease should continue to follow the guidance of their healthcare providers and adhere to recommended treatment plans. This research offers a glimmer of hope for the future, but it’s essential to rely on evidence-based medical advice and avoid self-treating.