Navigation Links
New model suggests feared side effect of Alzheimer's drugs is unlikely
Date:6/17/2010

The first trial of a new model for testing Alzheimer's treatments has reassured researchers that a promising class of drugs does not exacerbate the disease if treatment is interrupted.

Scientists at Washington University School of Medicine in St. Louis and Merck & Co. Inc studied the effects of a class of drugs known as gamma secretase inhibitors. Researchers had worried that these drugs might cause a build-up of proteins linked to Alzheimer's disease and that this build-up could be unleashed in a surge when patients went off the medications. But the new study suggests that they do not.

"This is important because it eases some concerns that have been raised about this potentially useful class of medications," says senior author Randall Bateman, MD, a Washington University neurologist who treats patients at Barnes-Jewish Hospital.

The findings appeared recently in The Journal of Neuroscience.

Gamma secretase inhibitors block proteins involved in the creation of amyloid beta, the main ingredient of Alzheimer's plaques. Patients cannot continuously take these drugs because nonstop inhibition of the gamma secretase enzyme has harmful side effects. One study had revealed that when physicians temporarily halted used of the inhibitors in humans, amyloid beta levels in the blood surged. An animal study suggested cessation of treatment also led to an amyloid beta increase in the brain. Researchers have been watching for similar effects in current human clinical trials of gamma secretase inhibitors.

The new study used a technique for measuring production and clearance of amyloid beta developed by Bateman and his colleagues at Washington University. It was the first time stable-isotope-labeling kinetics (SILK) was used in primates.

In a preliminary assessment of normal amyloid beta production and clearance rates, scientists found that the amyloid beta turnover in the subjects, a group of rhesus macaques, was 10 percent per hour.

"This is much closer to the human turnover rate of 8 percent per hour than other animal models," says co-first author Kristin Wildsmith, PhD, a postdoctoral research scholar. "That means we can be more confident that preclinical testing of Alzheimer's treatments in this model will produce results that accurately predict what the effects will be in humans."

When scientists gave the animals gamma secretase inhibitors, SILK testing showed that the drugs reduced production of amyloid beta. When researchers stopped inhibitors, blood levels of amyloid beta increased above normal levels. But SILK showed there was no increase in amyloid beta levels in the central nervous system.

"It appears that blood testing may not be the best way to monitor amyloid beta levels in the central nervous system," says Bateman, who says that the source of amyloid beta in the blood is unclear.

Brain amyloid beta is a fragment of a larger protein regularly disassembled as a part of normal metabolism. Wildsmith showed that treatment with gamma secretase inhibitors shifts this disassembly from an amyloid-beta-producing path to an alternative pathway that precludes the production of amyloid beta.


'/>"/>

Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

Related medicine news :

1. University of Pennsylvania: Contrary to popular models, sugar is not burned by self-control tasks
2. Solid tumor modeling focus of workshops
3. PivotPoint Doubles Down on Business Process Modeling with Advanced BPMN 2 + UML 2 Training
4. NYU College of Dentistry, Penn State develop new model for investigating tobacco/oral cancer link
5. Jenny McCarthy - Actress, Activist, and Model - Dedicates bforacure's ‘breasts are beautiful' to Help Raise Money for Breast Cancer Charities
6. Same disease, different stem cell models
7. Wyatt Matas & Associates Releases White Paper on Future Home Healthcare Business Model
8. Super Fitness Bikini Model Mega-Mogul Jennifer Nicole Lee Goes Global, British TV Appearance, QVC London May 12th Sharing Top Fitness Products
9. Former USAA President and Leading, Industry Expert Launch Contact-Center Management Company Featuring Innovative Business Model
10. Second volume of groundbreaking Emerging Model Organisms series is released
11. Global Premiere: Jennifer Nicole Lee, Super Fitness Model & Mega Brand, Reveals Ab Circle Mini on HSN's World Launch
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/23/2017)... ... August 23, 2017 , ... TSC Advantage has been ... Risk Management Solution Innovations and Security Solution for Government Innovations. Both gold awards ... and its DHS SAFETY Act-designated enterprise security assessment approach. , The ninth annual ...
(Date:8/23/2017)... ... August 23, 2017 , ... The non-profit ... holding an inaugural State of the Science Symposium in partnership with the Global ... 2017. , This symposium provides a forum for global leaders in human nutrition ...
(Date:8/22/2017)... ... August 22, 2017 , ... The Women’s Choice Award, a ... Migraine Relief with the 2017 Women’s Choice Award. The identification by women of an ... out of 4 migraine sufferers are women. In a survey taken by the Women’s ...
(Date:8/22/2017)... ... August 22, 2017 , ... Western ... spoke at a popular international aesthetics conference for medical professionals about the positive ... patients’ health and his growing practice. , Dr. George K. Ibrahim ...
(Date:8/22/2017)... ... August 22, 2017 , ... Each of the past six years, Lightning Labels has sent ... these labels and stickers, demonstrating the variety and creativity of their designs. Submissions this year ... came in. Now, it's time to announce the winners of the sixth annual Photo Contest, ...
Breaking Medicine News(10 mins):
(Date:8/7/2017)... Diplomat Pharmacy, Inc. (NYSE: DPLO ) ... president, effective Aug. 7, 2017. ... other interests and will serve as president emeritus during a ... us in multiple leadership roles since he joined Diplomat with ... has provided decisive, strategic leadership which continues to benefit our ...
(Date:8/7/2017)... , Aug. 7, 2017  Endo International plc (NASDAQ: ... agreements to resolve virtually all known U.S. mesh product ... to resolve the known remaining U.S. claims at reasonable ... beginning in the fourth quarter of 2017 and continuing ... its second quarter 2017 results, the Company intends to ...
(Date:8/4/2017)... 3, 2017  Agragen, LLC, a ... the biopharmaceutical, nutraceutical, and aquacultural feed sectors, announces ... lead drug candidates, AGR131.  This drug is designed ... the blood of patients suffering from inflammatory conditions ... disease. Biological ...
Breaking Medicine Technology: