Mayo team spot­lights the role of senes­cent cells in neu­rode­gen­er­a­tion, start­ing down a path­way that may lead to Alzheimer’s

As an­ti-ag­ing re­search grows around the world, there’s been a big fo­cus on clear­ing away the “senes­cent” cells that clut­ter bod­ies as peo­ple grow old­er. These ag­ing cells lose the abil­i­ty to di­vide and mouse stud­ies have of­fered a pre­clin­i­cal the­o­ry that sweep­ing them away with new drugs can of­fer peo­ple longer, health­i­er lives.

Now a re­search team at the Mayo Clin­ic is of­fer­ing more an­i­mal da­ta to back that up, and they’re shin­ing a light on a new path­way in neu­rode­gen­er­a­tion and specif­i­cal­ly Parkin­son’s and Alzheimer’s — per­haps the sin­gle most frus­trat­ing field in drug de­vel­op­ment.

Ac­cord­ing to the Mayo team, they were able to de­ter­mine that mi­croglia and as­tro­cyte cells were most like­ly to turn in­to rogue zom­bies. By clear­ing these senes­cent cells from the brains of mice, they tar­get­ed a key path­way im­pli­cat­ed in Alzheimer’s, tamped down on in­flam­ma­tion and had an im­pact on mem­o­ry.

“We used a mouse mod­el that pro­duces sticky, cob­web like tan­gles of tau pro­tein in neu­rons and has ge­net­ic mod­i­fi­ca­tions to al­low for senes­cent cell elim­i­na­tion,” ex­plains first au­thor Tyler Buss­ian, a Mayo Clin­ic Grad­u­ate School of Bio­med­ical Sci­ences stu­dent. “When senes­cent cells were re­moved, we found that the dis­eased an­i­mals re­tained the abil­i­ty to form mem­o­ries, elim­i­nat­ed signs of in­flam­ma­tion, did not de­vel­op neu­rofib­ril­lary tan­gles, and had main­tained nor­mal brain mass.”

The work was pub­lished in Na­ture.

It’s a big leap — and an in­cred­i­bly com­plex chal­lenge — to go from a dis­ease mod­el in pre­clin­i­cal stud­ies to test­ing this con­cept in hu­mans. But bil­lions have been spent on Alzheimer’s with noth­ing but fail­ure to show for it. The theme now is try­ing new things, with a bet­ter un­der­stand­ing that bend­ing the curve of neu­rode­gen­er­a­tion in pa­tients who ex­hib­it symp­toms of their dis­ease will be ex­tra­or­di­nar­i­ly dif­fi­cult.

The most ad­vanced biotech in the senes­cence field is an up­start called Uni­ty, which was able to trans­late their pre­clin­i­cal work in­to a Phase I which starts with os­teoarthri­tis. But in­ves­ti­ga­tors in the field — in­clud­ing the team at Uni­ty — be­lieve they’re on a trail that leads to a host of ail­ments.

Alzheimer’s just may be one of them.


Im­age: Dar­ren Bak­er, se­nior au­thor, and Tyler Buss­ian.MAYO CLIN­IC

Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Idor­si­a's brain bleed drug flunks PhI­II tri­al, a decade af­ter pre­vi­ous flop

Idorsia’s long journey with clazosentan came to an abrupt “unexpected result” Monday morning with a Phase III flop.

The Swiss biopharma said the drug did not meet the main goal of the late-stage REACT study, conducted in the US, Canada and Europe since early 2019.

The 409-patient trial tested the intravenous drug’s ability to prevent complications due to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), in which blood vessels in the brain narrow and blood accumulates around the brain’s surface, which then dials up the pressure on the brain.

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Kenji Yasukawa, Astellas CEO (Photographer: Akio Kon/Bloomberg via Getty Images)

Astel­las taps chief strat­e­gy of­fi­cer as next CEO to 'go on the ag­gres­sive'

Five years into its big R&D revamp, Astellas says it’s time for a changing of the guard.

Kenji Yasukawa, who took over as president and CEO in 2018, will step down to become chairman of the board in April, making room for Naoki Okamura to take over. Okamura joined the company in 1986 and has served in a variety of finance, business and strategy roles, including most recently as chief strategy officer.

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Clin­i­cal tri­al di­ver­si­ty da­ta show mis­match be­tween en­roll­ment and dis­ease preva­lence, GSK says

A lack of diversity in clinical trials has persisted despite decades of initiatives to try to turn the tide.

In a recent review of 17 years of clinical trials, drugmaker GSK found that there were some mismatches between the demographics of its US-based trials and how prevalent diseases were in those populations.

The results, the company says, will help GSK and others design studies that better represent epidemiological rates within races and ethnicities.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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