Alzheimer’s senescent cell combination therapy presents promise

A Phase I trial employing the drug dasatinib has shown promise in clearing senescent cells in Alzheimer’s.

Recent drugs targeting beta-amyloid plaques have only yielded modest results, according to the study researchers. Instead, the current US study pursued cellular senescence as an alternative area of focus.

The findings published in Nature Medicine described how the US Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor dasatinib was used in combination with quercetin, a plant-derived flavonoid.

“In 2018, we found evidence of senescent cells in human Alzheimer’s,” stated Miranda Orr, PhD, Associate Professor of gerontology and geriatric medicine at Wake Forest University School of Medicine in the US.

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“Our previous research has shown that the combination of these two drugs target senescent cells and allow them to die,” Orr continued. “We know that they cleared senescent brain cells in Alzheimer’s mouse models, and they had already been shown to be safe in patients with other ailments.”

Method and results of the Alzheimer’s study

While the study was small, enrolling five participants aged 65 and older with symptoms of early-stage Alzheimer’s, data suggested that the combination therapy cleared amyloid from the brain and lowered inflammation in the blood.

Oral small-molecule multikinase inhibitor dasatinib plus quercetin was administered over two days. Then no drugs were given for a period of two weeks. The cycle was repeated six times for a total of 12 weeks.

Higher levels of dasatinib and quercetin levels were found in the blood, according to the paper. In four participants, dasatinib was detected in the cerebrospinal fluid (CSF). Quercetin was not detected in the CSF of any participants.

“We also determined that the treatment was safe, feasible and well-tolerated [in the Alzheimer’s patients],” Orr commented. “There were no significant changes in brain function as determined by assessing memory and brain imaging.”

Future research

This Phase I study is a “critical part of this pivotal moment in Alzheimer’s research as the focus shifts from amyloid and tau, the classic disease hallmarks, toward how the biology of aging underlies the disease,” stated Dr Howard Fillit, co-founder and Chief Science Officer at the Alzheimer’s Drug Discovery Foundation (ADDF).

A larger $3 million, Phase II clinical trial is in process, with the aim to test the effects of clearing senescent cells with the combination therapy, the paper noted.