Tuesday, January 31, 2023
THE SENIOR HEALTH LETTER
No Result
View All Result
  • Home
  • Home Care
  • Elder Care
  • Wellness
  • Dementia
  • Caregivers
  • Alzheimer’s
  • Assisted living
  • Mindfulness
  • Seniors advocate
The Senior Health Letter
No Result
View All Result
Home Alzheimer's

Stuart Lipton offers a new reason why all the Alzheimer’s drugs have failed – Endpoints News

Delmar by Delmar
April 1, 2021
in Alzheimer's
0
Stuart Lipton offers a new reason why all the Alzheimer’s drugs have failed – Endpoints News
0
SHARES
110
VIEWS
Share on FacebookShare on Twitter


There are a few com­mon­ly trot­ted out rea­sons for why vir­tu­al­ly every Alzheimer’s drug of the last two decades has failed:  Maybe the tri­als didn’t start ear­ly enough in the course of dis­ease, or maybe they didn’t go af­ter the right group of pa­tients?

As com­pa­nies have start­ed ear­li­er and on more se­lect groups of pa­tients, an­oth­er con­clu­sion has grown in­creas­ing­ly pop­u­lar: Maybe they’ve all gone af­ter the wrong tar­get. Maybe clear­ing the mis­fold­ed plaques that buildup in pa­tients’ brains, as these ther­a­pies have, just wipes away one symp­tom of the dis­ease but not the root cause.

Stu­art Lip­ton, though, has an al­ter­na­tive ex­pla­na­tion. A lead­ing de­men­tia ex­pert who helped de­vel­op the the last FDA-ap­proved Alzheimer’s drug, he pub­lished new re­search this week show­ing that the an­ti­bod­ies com­pa­nies de­vel­oped might be hav­ing an un­in­tend­ed side ef­fect that un­der­cuts any ben­e­fit they of­fer.

Amy­loid and tau-clear­ing an­ti­bod­ies, he wrote in a pa­per for the Pro­ceed­ing of the Na­tion­al Acad­e­my of Sci­ence, might be set­ting off dan­ger­ous in­flam­ma­tion that, in a cru­el bit of irony, has­ten neu­ro­log­i­cal de­cline.  Lip­ton called the re­sult para­dox­i­cal.

“We re­al­ized that it’s pos­si­ble these hu­man tri­als, many of which have failed, might be in part fail­ing be­cause they’re para­dox­i­cal­ly in­duc­ing more in­flam­ma­tion in the brain,” he told End­points News, “even though they’re get­ting rid of the pro­tein, which may be a good thing,”

Dorit Trudler

The re­search be­gan when a post­doc at Lip­ton’s Scripps In­sti­tute lab, Dorit Trudler, at­tempt­ed to make the in­nate im­mune cell of the brain, an oc­to­pus-look­ing goop called the mi­croglia, in the lab. It’s a dif­fi­cult task be­cause mi­croglia don’t come from the same lin­eage of stem cells in the bone mar­row that the rest of the im­mune sys­tem, B cells and T cells and macrophages, do.

In­stead, it comes from the yolk sac that bathes em­bryos in ear­ly de­vel­op­ment, mi­grat­ing from the sac to the brain. By giv­ing hu­man-de­rived stem cells a se­ries of mol­e­c­u­lar sig­nals, Trudler turned them in­to a clus­ter that re­sem­bled a yolk sac and, from it, de­vel­oped cells that, based on the mR­NA they ex­press, were in­dis­tin­guish­able from mi­croglia re­moved from hu­mans.

“They match as close­ly as pos­si­ble,” Lip­ton said.

Be­cause hu­man mi­croglia are dif­fi­cult to pro­duce, drug re­searchers have his­tor­i­cal­ly used mouse mod­els to see how the im­mune cells re­spond to drugs. Lip­ton and Tru­di, though, were able to sim­u­late how hu­man mi­croglia re­spond in the brain.

They found that if you ex­posed these mi­croglia to ei­ther al­pha synu­cle­in, the hall­mark mis­fold­ed pro­tein in Parkin­son’s, the mi­croglia sent off in­flam­ma­to­ry sig­nals. And if you added amy­loid-be­ta, the in­flam­ma­tion wors­ened.

Fi­nal­ly, they man­aged to ob­tain an­ti­bod­ies that com­pa­nies had de­vel­oped to bind to and clear those mis­fold­ed pro­teins. (Lip­ton de­clined to say which an­ti­body it was, ex­cept that, de­spite his best ef­forts to con­vince the drug­mak­er, it wasn’t Bio­gen’s ad­u­canum­ab, the con­tro­ver­sial can­di­date now be­fore the FDA.)

To their sur­prise, the an­ti­bod­ies suc­cess­ful­ly bind­ed to the mis­fold­ed pro­tein but that didn’t help in­flam­ma­tion. “Rather than make things bet­ter, it ac­tu­al­ly made things worse,” Lip­ton said.

By look­ing at hu­man­ized mice that had both hu­man and mice mi­croglia, Lip­ton’s team found that the pro-in­flam­ma­to­ry re­sponse was unique to the hu­man cells, mean­ing drug­mak­ers wouldn’t have seen it in the trans­la­tion­al stud­ies. They’re still not sure why it’s caus­ing in­flam­ma­tion, but they showed the ef­fect with mul­ti­ple dif­fer­ent an­ti­bod­ies that tar­get mul­ti­ple dif­fer­ent pro­teins and they’ve nailed down the path­way, NL­RP3, that’s in­volved.

Still, Lip­ton said, they don’t nec­es­sar­i­ly have to fig­ure out the ex­act mech­a­nism. He says you could imag­ine giv­ing these amy­loid-clear­ing drugs in com­bi­na­tion with a drug that blocks in­flam­ma­tion, al­low­ing doc­tors to clear out mis­fold­ed pro­teins with­out dan­ger­ous­ly turn­ing up the heat.

In fact, it’s what his lab is work­ing on right now.

“We’re hope­ful that we can maybe de­vel­op a drug in the near fu­ture that can off­set,” Lip­ton said.



Source link

Tags: AlzheimersDrugsEndpointsfailedLiptonNewsoffersreasonStuart
Advertisement Banner
Previous Post

Relaxed visiting rules take effect at B.C. long-term care facilities

Next Post

Spring Valley fire: Officials provide update on deadly fire at assisted living facility

Delmar

Delmar

Next Post
Spring Valley fire: Officials provide update on deadly fire at assisted living facility

Spring Valley fire: Officials provide update on deadly fire at assisted living facility

Discussion about this post

Recommended

Pleasanton: Community of Character announces scholarship winners | News

Pleasanton: Community of Character announces scholarship winners | News

2 years ago
Amazon to Take Its Telehealth Service Nationwide

Amazon to Take Its Telehealth Service Nationwide

2 years ago

Don't Miss

(2021-2026) Nursing Home Beds Market Size, Demand Status | Global Industry Segment Analysis, Growing Status of Key Players

Advice You Need To Know About Personal Development

May 12, 2021
Asceneuron Receives USD 2.2 Million Award from the Alzheimer’s Drug Discovery Foundation

Advocate Aurora Enterprises acquires national leader in home care and wellness offerings Senior Helpers

April 1, 2021
‘I’m in jail’: BPS mothers and caregivers voice concerns with district reopening plans

‘I’m in jail’: BPS mothers and caregivers voice concerns with district reopening plans

April 1, 2021
As Loved Ones Reunite After A Year, Dementia Experts Offer These Tips

As Loved Ones Reunite After A Year, Dementia Experts Offer These Tips

April 1, 2021

Categories

  • Alzheimer's
  • Assisted living
  • Caregivers
  • Dementia
  • Elder Care
  • Home Care
  • Mindfulness
  • Seniors advocate
  • Uncategorized
  • Wellness

Follow us

Recent News

(2021-2026) Nursing Home Beds Market Size, Demand Status | Global Industry Segment Analysis, Growing Status of Key Players

Advice You Need To Know About Personal Development

May 12, 2021
Asceneuron Receives USD 2.2 Million Award from the Alzheimer’s Drug Discovery Foundation

Advocate Aurora Enterprises acquires national leader in home care and wellness offerings Senior Helpers

April 1, 2021
April 2021
S M T W T F S
 123
45678910
11121314151617
18192021222324
252627282930  
« Mar   May »
  • About Us
  • Contact Us
  • Privacy & Policy

© 2021 The Senior health Letter

No Result
View All Result
  • Home
  • Home Care
  • Elder Care
  • Wellness
  • Dementia
  • Caregivers
  • Alzheimer’s
  • Assisted living
  • Mindfulness
  • Seniors advocate

© 2021 The Senior health Letter