Young an­ti-ag­ing field takes big step with Mayo Clin­ic senolyt­ics show­case

The idea that flush­ing senes­cent cells — those old, fa­tigued cells that cease to di­vide — from the body may rid the body of harm­ful pro­teins has been one of the promi­nent pro­pos­als in the an­ti-ag­ing sphere. Hav­ing gen­er­at­ed a stream of an­i­mal da­ta to sup­port the hy­poth­e­sis, the Mayo Clin­ic now has re­sults from an ear­ly hu­man study sug­gest­ing they have found drugs that can do ex­act­ly that.

Latonya Hick­son

To be sure, the main goal of the Phase I tri­al wasn’t to show the ef­fects of de­creas­ing senes­cent cells in the body; rather, the sci­en­tists were keen to prove that a senolyt­ic reg­i­men they’ve test­ed in mice works the same way in hu­mans.

This is sig­nif­i­cant be­cause de­spite the pub­li­ca­tion of first-in-hu­man da­ta in Jan­u­ary, “so far, there has been no di­rect demon­stra­tion of senes­cent cell clear­ance by senolyt­ic drugs in peer-re­viewed pub­lished hu­man clin­i­cal tri­als,” the au­thors wrote in EBio­Med­i­cine.

For the small tri­al, re­searchers de­ployed dasa­tinib and quercetin; the for­mer is a can­cer drug al­so known as Spry­cel while the lat­ter is a plant de­riv­a­tive. Nine pa­tients with di­a­betes-re­lat­ed chron­ic kid­ney dis­ease were re­cruit­ed and giv­en the treat­ments for three days.

Laris­sa Langhi Pra­ta

While the drugs were out of the sys­tem with­in a few days, the ef­fects ap­peared to per­sist, the team — with LaTonya Hick­son and Laris­sa Langhi Pra­ta as the co-first au­thors — re­port­ed:

Key mark­ers of senes­cent cell bur­den were de­creased in adi­pose tis­sue and skin biop­sied from sub­jects 11 days af­ter com­plet­ing the 3-day course of D + Q, as were key cir­cu­lat­ing SASP fac­tors, com­pared to be­fore ad­min­is­tra­tion of these senolyt­ic drugs.

Such proof about the mech­a­nism of ac­tion bol­sters their pre­vi­ous work sug­gest­ing that a brief course of dasa­tinib plus quercetin im­proved phys­i­cal func­tions for pa­tients with id­io­path­ic pul­monary fi­bro­sis — a tough-to-treat dis­ease.

While small-scale, the tri­al is a sig­nif­i­cant step for­ward for the trans­la­tion of senolyt­ic ther­a­pies, ac­cord­ing to Ronald Ko­han­s­ki, deputy di­rec­tor of the di­vi­sion of ag­ing bi­ol­o­gy at the Na­tion­al In­sti­tute of Ag­ing.

“The demon­stra­tion that senes­cent cell num­bers can be re­duced in two tis­sues in hu­mans is an im­por­tant ad­vance based on the com­pelling ev­i­dence from stud­ies in lab­o­ra­to­ry mice,” he said in a state­ment.

James Kirk­land

Chron­ic kid­ney dis­ease is just one of many age-re­lat­ed ail­ments that the team be­lieves senolyt­ics can de­lay, pre­vent or treat, said se­nior au­thor James Kirk­land (who heads Mayo’s Robert and Ar­lene Ko­god Cen­ter on Ag­ing).

His col­leagues at Mayo have pre­vi­ous­ly flagged Alzheimer’s and Parkin­son’s as dis­eases where purg­ing senes­cent cells can make a big dif­fer­ence.

In case any­one gets over­ly ex­cit­ed, though, the sci­en­tists felt the need to con­clude their pa­per with a note of cau­tion:

The field of senolyt­ics is new. The first clin­i­cal tri­al of senolyt­ic agents was on­ly re­port­ed in Jan­u­ary 2019. The find­ings re­port­ed here are pre­lim­i­nary re­sults from an on­go­ing clin­i­cal tri­al of senolyt­ics for treat­ing dys­func­tion in pa­tients with di­a­bet­ic chron­ic kid­ney dis­ease. Few­er than 150 sub­jects have been treat­ed with these drugs in the con­text of clin­i­cal tri­als that we are aware of so far. In ad­di­tion to side ef­fects re­lat­ed to in­di­vid­ual senolyt­ic drugs known from oth­er con­texts in which those drugs have been used, there could turn out to be se­ri­ous side-ef­fects of senolyt­ics as a class, which are not yet known. We cau­tion against the use of senolyt­ic agents out­side the con­text of clin­i­cal tri­als un­til more is known about their ef­fects and side ef­fects.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Hal Barron, GSK via YouTube

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A little over a week ago, GSK R&D chief Hal Barron marked his third anniversary at the research helm by taking a turn at the virtual podium during JP Morgan to make the case that he and his team had built a valuable late-stage pipeline capable of churning out more than 10 blockbusters in the next 5 years.

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Janet Woodcock (AP Images)

End­points poll: Janet Wood­cock takes the (in­ter­im) helm at the FDA. And a large ma­jor­i­ty of our read­ers want her to stay there

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Janet Woodcock and Joshua Sharfstein (AP, Images)

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Hal Barron, GSK R&D chief (GSK via YouTube)

Glax­o­SmithK­line's $4B bis­pe­cif­ic can­cer drug al­liance with Mer­ck KGaA hit by big set­back with a PhI­II fail­ure on NSCLC

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Charlie Fuchs, Roche and Genentech global head of product development for oncology and hematology (Yale Cancer Center)

Yale can­cer spe­cial­ist Char­lie Fuchs tapped as new glob­al de­vel­op­ment chief for Roche/Genen­tech

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