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Innovative Approach to Alzheimer’s: Preliminary Study Safely Addresses Senescent Cells
Researchers are probing the relationship between cellular senescence and Alzheimer’s disease. These aged and malfunctioning cells, which harm adjacent healthy cells, have been found in patients with Alzheimer’s. An early study using a repurposed cancer medication (dasatinib) in conjunction with an antioxidant (quercetin) reveals promising outcomes in targeting these cells.
The Role of Cellular Senescence in Alzheimer’s Disease
Scientists at Wake Forest University are investigating the influence of cellular senescence on Alzheimer’s. Utilizing a recycled cancer medication and an antioxidant, initial tests suggest promise in targeting these troublesome cells, although larger-scale studies are necessary for verification.
Alzheimer’s is the most prevalent form of dementia, affecting over 6.5 million Americans as per the Alzheimer’s Association. Despite advancements in pharmaceuticals targeting beta-amyloid plaques—a key feature of Alzheimer’s—the results have been somewhat disappointing.
Recent Developments
Researchers at Wake Forest University School of Medicine have released results from a Phase I trial that examined another promising area—cellular senescence. The research findings were made public on September 7 and appeared in the scientific journal Nature Medicine.
Senescent cells are aging, defective cells unable to perform proper self-repair and fail to undergo programmed cell death. These cells behave anomalously, releasing substances that lead to the death of adjacent healthy cells and inflammation. Over time, they accumulate in various bodily tissues, contributing to aging, cognitive decline, and cancer.
Previous Discoveries and Current Studies
“In 2018, we discovered the presence of senescent cells in human Alzheimer’s disease,” mentioned Miranda Orr, Ph.D., an associate professor of gerontology and geriatric medicine at Wake Forest University School of Medicine. “Our studies in mouse models also revealed their role in causing loss of brain cells, inflammation, and memory impairment.”
Therapeutic Reapplication of Existing Drugs
For treatment, researchers employed a drug, dasatinib, previously approved by the U.S. Food and Drug Administration for cancer treatment, along with quercetin, a flavonoid derived from plants.
“Earlier studies have demonstrated that this drug combination targets senescent cells, facilitating their death,” Orr stated. “In Alzheimer’s disease mouse models, these drugs succeeded in clearing senescent cells in the brain and have been proven safe for other conditions.”
Findings from Phase I Trial
The recent study enrolled five participants, aged 65 and above, displaying symptoms of early-stage Alzheimer’s. The subjects were administered oral dasatinib and quercetin for two consecutive days, followed by a two-week break. This cycle was repeated for a total of 12 weeks.
“Our chief aim was to ascertain whether these drugs could penetrate the central nervous system,” said Orr. “Cerebrospinal fluid samples were collected before and after drug administration.”
Monitoring side effects and evaluating various biomarkers in cerebrospinal fluid and blood helped in assessing the drugs’ safety and effectiveness. The study found increased levels of both drugs in the blood, and dasatinib was also detected in the cerebrospinal fluid in four participants.
“The treatment appeared safe, feasible, and well-tolerated,” Orr reported, cautioning against drawing extensive conclusions due to the small sample size and absence of a placebo arm for comparison.
Future Directions
The research team observed indications that the drug combination reduced amyloid levels in the brain and diminished inflammation in the bloodstream. However, they also detected a rise in inflammatory biomarkers in the cerebrospinal fluid.
“We need to scrutinize this in our subsequent trial,” Orr said, acknowledging that this could indicate either an initial increase in inflammation upon clearing senescent cells or perhaps inflammation associated with the treatment itself.
Concluding Remarks
“Miranda Orr’s work is integral at this transformative juncture in Alzheimer’s research,” stated Howard Fillit, M.D., co-founder and chief science officer at the Alzheimer’s Drug Discovery Foundation. “We must broaden our approach, exploring new therapeutic avenues like senolytics that target biological aging, the leading risk factor for Alzheimer’s.”
The research team is preparing for a larger, $3 million, Phase II clinical trial, funded by the ADDF, to explore the efficacy of this combination therapy in a broader population.
“The preliminary data validates proceeding with a larger study population and a placebo control group,” concluded Orr. “We are eager to further investigate how this treatment affects Alzheimer’s disease biomarkers.”
References
The study received financial backing from multiple organizations, including the Alzheimer’s Drug Discovery Foundation, the National Institutes of Health, the National Institute on Aging, and other specialized centers and foundations.
The research was published on September 7, 2023, in the journal Nature Medicine, with a DOI reference of 10.1038/s41591-023-02543-w.
Frequently Asked Questions (FAQs) about Alzheimer’s research
What is the main focus of the research conducted by Wake Forest University on Alzheimer’s disease?
The primary focus of the research is to explore the role of senescent cells in Alzheimer’s disease. Scientists at Wake Forest University School of Medicine are investigating how these aged, dysfunctional cells may contribute to the condition and are conducting a Phase I trial to test a therapy targeting these cells.
What drugs are being repurposed for this Alzheimer’s study?
The researchers have repurposed a U.S. FDA-approved cancer drug called dasatinib and have combined it with an antioxidant known as quercetin. Initial results from Phase I trials suggest that this combination could target senescent cells effectively.
How many participants were involved in the Phase I trial?
The Phase I trial enrolled five participants, all of whom were 65 years and older and exhibited symptoms of early-stage Alzheimer’s disease.
What were the primary outcomes of the Phase I trial?
The primary outcomes included determining whether the drugs penetrated the central nervous system and assessing their safety and efficacy. Dasatinib levels were detected in the cerebrospinal fluid (CSF) in four subjects. No significant changes in brain function were observed, indicating the treatment was safe for further evaluation.
What is the significance of senescent cells in Alzheimer’s disease?
Senescent cells are aged and dysfunctional cells that do not die off as they should. They release substances that damage neighboring healthy cells and cause inflammation. These cells have been found to contribute to various health issues, including the aging process, neurocognitive decline, and cancer.
What are the future prospects for this research?
The research team plans to proceed with a larger $3 million, Phase II clinical trial funded by the Alzheimer’s Drug Discovery Foundation (ADDF). They aim to further test the effects of clearing senescent cells with the combination therapy on a larger population and include a placebo arm for comparative results.
What were the sources of funding for this study?
The study was supported by numerous agencies and foundations, including the Alzheimer’s Drug Discovery Foundation, National Institutes of Health/National Institute on Aging, and the U.S. Department of Veterans Affairs, among others.
Who were the co-leaders of the study?
The study was co-led by Mitzi Gonzales, Ph.D., of The University of Texas Health Science Center at San Antonio, and Miranda Orr, Ph.D., associate professor of gerontology and geriatric medicine at Wake Forest University School of Medicine.
More about Alzheimer’s research
- Alzheimer’s Association Statistics
- Journal Publication in Nature Medicine
- Wake Forest University School of Medicine
- Alzheimer’s Drug Discovery Foundation (ADDF)
- U.S. Food and Drug Administration (FDA) on Dasatinib
- Study on Cellular Senescence and Aging
- National Institutes of Health (NIH) Funding Information
- U.S. Department of Veterans Affairs Research Funding
5 comments
Wow, this is groundbreaking stuff! Finally, some hope for Alzheimer’s patients. Maybe this is the next big step? Good on Wake Forest for this research.
repurposing drugs, huh? I guess that’s one way to speed up the whole research and testing process. Clever, if you ask me.
can’t help but wonder about the long term effects though. It’s just Phase I but promising for sure. Eager to see more on this.
Didn’t think Id see the day when cancer drugs are used for Alzheimer’s. Seems a bit far-fetched but hey, if it works it works.
As someone who’s had to watch family go through Alzheimer’s, this gives me some hope. Keeping my fingers crossed for Phase II results.