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

A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Su­per-se­cre­tive an­ti-ag­ing biotech Cal­i­co tees up the first vis­i­ble clin­i­cal tri­al of an ex­per­i­men­tal drug. And it’s for can­cer?

Over the past 7 years, Calico has been so much more than your average, run-of-the-mill secretive biotech players. It’s a riddle, wrapped in a mystery, inside an enigma, to repurpose an old Winston Churchill line dating from the time he confronted the Iron Curtain surrounding Stalin’s thoughts.

Launched by industry legend Art Levinson of Genentech fame, with the infinitely deep pockets of Google for support, one of the few big headlines the anti-aging biotech has sparked focused on a major alliance with AbbVie — a giant outfit that conversely likes to show off its drug prospects whenever it can. Together, they’ve been focused on diseases that limit life span — quite an arc of ailments.

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RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

As catalysts go, few loom larger than the aducanumab adcomm slated for Nov. 6.

With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

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Covid-19 roundup: Pars­ing Bourla, a top an­a­lyst sees im­proved chances for Pfiz­er vac­cine; Fau­ci: No sur­prise that Trump was hit by Covid-19

With a medley of adverse events hobbling the late-stage development of vaccines and drugs, Pfizer CEO Albert Bourla’s latest — extended — timeline for the mRNA approach they’re working on with BioNTech is giving some top analysts added confidence that the pharma giant can come up with the regulatory goods next month.

Parsing Bourla’s language in his comments last week, SVB Leerink’s Geoffrey Porges notes that Bourla’s decision to say they “may” be able to nail down the positive efficacy of their vaccine in a matter of days — a big change from his earlier certainty — may also indicate a delay on that to early November.

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News brief­ing: Ab­b­Vie and Roche's Ven­clex­ta scores an­oth­er FDA OK; Im­muno­Gen nabs Chi­na deal with $40M cash

AbbVie and Roche’s Venclexta has gotten a new FDA thumbs up.

The pair announced Monday that regulators have approved the drug in combination with azacitidine or low-dose cytarabine for newly-diagnosed acute myeloid leukemia in adults who are 75 or older or those who can’t undergo intensive chemotherapy. This follows the drug’s accelerated approval in 2018 and positive data from two Phase III confirmatory trials.

James Sabry (Roche)

Roche's James Sabry inks his sec­ond AI deal in back-to-back pacts — this time part­ner­ing Genen­tech with Stan­ford spin­out Gen­e­sis Ther­a­peu­tics

Less than a week after Roche joined forces with Dyno Therapeutics to develop gene therapies using artificial intelligence, its giant subsidiary Genentech is hopping on the AI bandwagon with a different player.

Genentech has inked a deal with Stanford spinout Genesis Therapeutics to harness its AI power for drug development and discovery. Genesis is getting an upfront payment and milestones, but the companies are keeping the details under wraps for now. The Burlingame, CA-based biotech also stands to earn future royalties on any approved Genentech drugs that come from the deal.

Joe Biden (Carolyn Kaster, AP Images)

What about the Ger­man ne­go­ti­a­tion mod­el? Biden steers drug pric­ing de­bate to a show­down

From an ill-fated proposal to ban rebates for pharmacy benefit managers to an executive order demanding a “most-favored-nation price” for Medicare, if nothing else President Donald Trump has introduced Americans to a flurry of ideas to rein in pharma, an industry he once accused of “getting away with murder.” And now we’re getting the first glimpse of what a Joe Biden presidency might mean for prescription drug pricing.

En­do pays $658M in a fur­ther bet on col­la­gen-based med­i­cines, buy­ing out long­time bio­phar­ma part­ner

A little less than two years after Endo Pharmaceuticals’ deal to purchase Somerset Therapeutics fell through, the Irish drugmaker is returning to the well with a much bigger acquisition.

Endo has agreed to buy BioSpecifics Technologies for a whopping $658 million, the two companies announced Monday, in the culmination of a research agreement signed all the way back in 2004. Endo will purchase all of BioSpecifics’ outstanding stock for about $540 million, valuing the company at $88.50 per share — a 45% premium on the $61.02 share price at which the company closed on Friday.

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Gilead feels the heat as close al­ly Gala­pa­gos re­ports a big set­back on one of their top ex­per­i­men­tal drugs

The bad news keeps stacking up at Galapagos — which quite likely just lost control of a billion-dollar deal — and by extension their close partners at Gilead.

The biotech $GLPG reported after the bell Thursday that GLPG1972, one of their top development programs, flat failed a mid-stage study for osteoarthritis, flunking the primary and all secondary endpoints.

Testing 3 different doses of their drug, which relies on ADAMTS-5 inhibition, investigators concluded that none of them triggered a statistically significant response — as measured by cartilage thickness.

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