Team de­vel­op­ing COVID drug to re­verse ag­ing

Stamford Advocate - - NEWS - By Jor­dan Fen­ster

The older you are, the more likely your COVID-19 in­fec­tion will be more se­vere, and even fa­tal. Of the nearly 5,000 COVIDre­lated deaths in Con­necti­cut to date, 81 per­cent are peo­ple over 70 years old.

But what if you could turn back the clock? A team of re­searchers at the Univer­sity of Con­necti­cut are work­ing on ways to lit­er­ally re­verse the ef­fects of ag­ing as a way to mit­i­gate the sever­ity of a COVID in­fec­tion.

“The goal here is not to erase ag­ing, but rather we’re test­ing in­ter­ven­tions that are de­signed to slow the rate of bi­o­log­i­cal ag­ing and there­fore help pre­vent se­vere COVID,” ac­cord­ing to Ge­orge Kuchel, di­rec­tor of UConn’s Cen­ter on Ag­ing and chief of geri­atric medicine at UConn Health.

One drug in par­tic­u­lar, called com­pound RTB101, can the­o­ret­i­cally not only slow ag­ing but boost the im­mune re­sponse, help­ing the body and any po­ten­tial vac­cines do their jobs bet­ter.

That’s im­por­tant be­cause, as Kuchel said, “these vac­cines don’t work as well on older adults.”

“Even if the vac­cine turns out to be as ef­fec­tive as the ini­tial stud­ies sug­gest, there’s a very strong like­li­hood that it’s go­ing to be less ef­fec­tive in older adults,” he said. “These kinds of ap­proaches are go­ing to be im­por­tant as ad­di­tional ther­a­pies to the vac­cine, for the vac­cine alone is not go­ing to be suf­fi­cient.”

Another weak­ness of any po­ten­tial vac­cine is its speci­ficity. The COVID-19 pan­demic may be con­tained, but the virus could mu­tate, or another virus might emerge.

“At some point, we’re go­ing to be done with COVID-19, hope­fully,” Kuchel said. “But I think we all agree that there could very well be another COVID, whether it’s COVID-21, -22, what­ever, or another pathogen out there that we don’t even know about yet.

“And if older adults are more vul­ner­a­ble to get this and to die from it, then we be­lieve this ap­proach will be help­ful ir­re­spec­tive of what the in­fec­tion is.”

How it works

The com­pound known as RTB101 doesn’t ac­tu­ally make you younger. There’s a dif­fer­ence,

Kuchel said, be­tween chrono­log­i­cal age — how many years you have been alive — and bi­o­log­i­cal age.

“Whereas bi­o­log­i­cal ag­ing is an ef­fort to cap­ture the rate of ag­ing, how fast some­body ages,” Kuchel said. “As you can imag­ine, you could have two peo­ple who are both 70 years old, and one could have a bi­o­log­i­cal age which would be younger than most 70-yearolds, and another one who has a bi­o­log­i­cal age that would be older than most 70-year-olds.”

RTB101 tar­gets the bi­o­log­i­cal path­ways that con­trol the ag­ing process, the so-called “mTOR path­way,” for ex­am­ple.

Early ver­sions of the com­pound have been stud­ied for decades — at Con­necti­cut’s Jack­son Labs and else­where — and have been shown to slow ag­ing in mice.

While in­hibit­ing the natural pro­cesses that lead to bi­o­log­i­cal ag­ing, the com­pound also boosts the body’s abil­ity to fight dis­ease.

“There are a lot of genes that are in­volved in our abil­ity to fend off vi­ral in­fec­tions,” Kuchel said. “There are these in­flam­ma­tory molecules called ‘in­ter­feron gamma.’ That whole fam­ily of molecules is very im­por­tant to our abil­ity to fend off in­fec­tion, par­tic­u­larly vi­ral in­fec­tions. What this com­pound does is it boosts those re­sponses. So it down-reg­u­lates mTOR and it up reg­u­lates the in­ter­feron gamma re­sponses.”

“In a sense, it kind of re­sets the body to be­have the way it would have at a younger age, and to boost im­mune re­sponses,” Kuchel said.

Time­lines

The work on RTB101 is be­ing funded by the Na­tional In­sti­tutes for Health and the first step — which the team at UConn is cur­rently re­cruit­ing sub­jects for — is a small-scale fea­si­bil­ity study in­volv­ing peo­ple over the age of 65 who have ei­ther been re­cently di­ag­nosed with a COVID-19 in­fec­tion or who lives with some­one di­ag­nosed with COVID in the last few days.

“We’re in a very tight time­line,” Kuchel said. “We need to do this in the next two months.”

But don’t ex­pect your doc­tor to pre­scribe an anti-ag­ing drug any time soon.

Af­ter the fea­si­bil­ity study will come a large-scale, multi-site clin­i­cal trial. Only then will Kuchel and his team seek FDA ap­proval.

“I know that some­times the progress of sci­ence seems mad­den­ingly slow. But un­for­tu­nately, it’s the only way we can show that it works,” Kuchel said. “In terms of this be­ing avail­able at physi­cian’s of­fices, it’s not go­ing to be within the next year or two. This is go­ing to take some time.”

But, again, this sort of re­search could be im­por­tant, Kuchel said, be­cause it is not a ther­apy to treat or pre­vent any spe­cific dis­ease.

“We be­lieve that will be trans­for­ma­tive not only for the cur­rent COVID pan­demic, but for fu­ture pan­demics, fu­ture in­fec­tions, which we know are go­ing to hap­pen,” he said.

“We know that fu­ture in­fec­tions will hap­pen, we know that older adults will be more vul­ner­a­ble. That’s ab­so­lutely clear. The only thing we don’t know is what the pathogen will be.

“With this ap­proach, the ar­gu­ment can be made that we don’t need to know what that pathogen is be­cause we’re not tar­get­ing the pathogen, we’re tar­get­ing the per­son.”

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