A Continued Painfully Slow Assessment of the Dasatinib and Quercetin Senolytic Treatment in Human Trials

A single course of treatment with the combination of dasatinib and quercetin clears meaningful numbers of senescent cells from aged human tissues, and to much the same degree as it does in mice. In mice this treatment dramatically, rapidly reverses signs of age-related disease. The research community has known this for the better part of a decade, with ever more studies added over this time. Near every age-related condition is reversed to some degree via the use of senolytic therapies that can selectively clear senescent cells, with dasatinib and quercertin continuing to be one of the better treatments, comparing those with published data.

One might think that there would be a rush to demonstrate that this cheap drug and supplement combination works in humans, and could therefore be used widely to improve late-life health by reducing the burden of senescent cells in near every older person. But no. Only a few studies have been conducted, tentatively. Today's research materials report on another of these efforts, a small phase 1 clinical trial that tells us nothing about efficacy, and only what we already knew about safety, that dasatinib and quercetin are safe for older people to use at senolytic doses and dosage schedules. The incentives operating in the clinical development community are such that any cheap, existing drug is unlikely to receive much attention, no matter how good it is. Vast sums are devoted to making new senolytic drugs, while a drug that might achieve a great deal of good in the world is left on the shelf.

That situation won't change any time soon, but there is a role for philanthropy here. It would not require all that much in funding to run a half dozen informal, hundred-participant clinical trials, on the scale of the PEARL trial for rapamycin, to demonstrate that, yes, dasatinib and quercertin is as good as we suspect it to be. The purpose would not be to demonstrate this point to the FDA, as dasatinib is already approved and quercetin is a supplement, and so these could be very lean trials, absent all the regulatory overhead and its costs. The goal is rather to demonstrate the merits and safety of this senolytic therapy to the physicians who can choose to prescribe off-label.

Phase I Clinical Trial Shows Treatment Designed to Clear Senescent Cells in Alzheimer's Disease is Safe

Senescent cells are old, sick cells that cannot properly repair themselves and don't die off when they should. Instead, they function abnormally and release substances that kill surrounding healthy cells and cause inflammation. Over time, they continue to build up in tissues throughout the body contributing to the aging process, neurocognitive decline and cancer.

For the current study, the research team enrolled five participants aged 65 and older with symptoms of early-stage Alzheimer's disease. Participants received oral dasatinib plus quercetin over two consecutive days, followed by two weeks of no drugs. The cycle repeated six times for a total of 12 weeks. The research team also collected data on the safety and efficacy of the two drugs by monitoring side effects. They assessed biomarkers of senescence in cerebrospinal fluid (CSF) and blood, and also evaluated patients' cognition and brain images before treatment and after they completed the 12-week study. They found that both dasatinib and quercetin levels increased in the blood, and dasatinib was detected in the CSF in four subjects. Quercetin was not detected in the CSF of any participant. "We also determined that the treatment was safe, feasible and well-tolerated. There were no significant changes in brain function as determined by assessing memory and brain imaging to provide additional evidence that it is a safe therapy to evaluate further." Researchers also saw evidence to suggest that the combination therapy cleared amyloid from the brain and lowered inflammation in the blood. "However, we shouldn't over-interpret these results. There was a small number of people enrolled, there was no placebo arm to compare results."

Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial

Cellular senescence contributes to Alzheimer's disease (AD) pathogenesis. An open-label, proof-of-concept, phase I clinical trial of orally delivered senolytic therapy, dasatinib (D) and quercetin (Q), was conducted in early-stage symptomatic patients with AD to assess central nervous system (CNS) penetrance, safety, feasibility, and efficacy. Five participants (mean age = 76 years) completed the 12-week pilot study.

D and Q levels in blood increased in all participants. In cerebrospinal fluid (CSF), D levels were detected in four participants (80%) Q was not detected. The treatment was well-tolerated, with no early discontinuation. Secondary cognitive and neuroimaging endpoints did not significantly differ from baseline to post-treatment further supporting a favorable safety profile.

CSF levels of interleukin-6 (IL-6) and glial fibrillary acidic protein (GFAP) increased with trending decreases in senescence-related cytokines and chemokines, and a trend toward higher Aβ42 levels. In summary, CNS penetrance of D was observed with outcomes supporting safety, tolerability, and feasibility in patients with AD. Biomarker data provided mechanistic insights of senolytic effects that need to be confirmed in fully powered, placebo-controlled studies.


It's even worse with high dose Fisetin . It's like they don't even want to release the results because it can't be patented.

Posted by: Mike Best at September 14th, 2023 3:28 PM

How much would that lean trial cost? If it really wouldn't be that high a cost, it could be crowdfunded.

Posted by: Matthew at September 14th, 2023 4:33 PM

I have been doing my own n=1 research on D&Q since 2018. Dosing Once every six months. I have settled on a dose of 240mg D, 2500mg Q, simply because that is the point at which I begin to feel side effects. I would like to do a higher dose, but can find no source to confirm safety at a higher dose. The Abstract for this study does not specify the dose, anyone know what dose was used in this study?

Posted by: JohnD at September 14th, 2023 6:08 PM

Interesting JohnD. I have done a few rounds of high dose liposomal Fisetin + Q and I seemed to get an effect. The first round I really felt with crazy dreams for a few days like maybe it was working on cells up there. I felt better a few weeks after using it. If anyone uses Fisetin it has to be high dose liposomal or you won't absorb enough of it.

Posted by: Mike Best at September 14th, 2023 6:15 PM

Oooh... A new Kirkland study. Me likez. Haz Lulz:
Best LUL! of long list of lulleries:
Dasatinib plus quercetin prevents uterine age-related dysfunction and fibrosis in mice
'...the title is wrong and deceitful: the data do not indicate a prevention of uterine age-related dysfunction and fibrosis in mice by D+Q. With the data presented here, this claim is wrong. This is utterly surprising since the text in the article clearly states that D+Q does not prevent uterine fibrosis.'
Oops. The list goes on and on. Lots of studies with Kirkland involvement with problematic data and authors who don't or can't provide original raw data.
Even Mirranda E. Orr, featured in this article's provided link started her carreer with 'image problems' in her thesis and failed to provide original data also for a later study with her name on.
Painfully slow research? More like painfully often faked research.

Posted by: Jones at September 15th, 2023 1:35 AM

Can anyone provide guidance on obtaining Dasatinib? I'm wondering if there is a listing somewhere of members of the medical community who are willing to help.

Posted by: Frank at September 15th, 2023 4:33 AM

There is no leadership in the head-on collision between perpetual collaborators: big teaching hospital that stumbled onto it, big pharma, cdc, and: those looking to increase heathspan.

Posted by: JDB at September 17th, 2023 1:11 AM

Haven't you figures it out yet regarding the FDA? Suggest you spend a few minutes keeping up with Edward Dowd every week. You'll figure it out quickly.

Posted by: Tom Schaefer at September 20th, 2023 7:29 AM
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