Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New model suggests feared side effect of Alzheimer's drugs is unlikely

18.06.2010
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.

Cook JJ, Wildsmith KR, Gilberto DB, Holahan MA, Kinney GG, Mathers PD, Michener MS, Price EA, Shearman MS, Simon AJ, Wang JX, Wu G, Yarasheski KE, Bateman RJ. Acute gamma-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-beta production to alternative APP fragments without amyloid-beta rebound. Journal of Neuroscience 2010 30: 6743-6750.

Funding from Merck, the National Institute on Aging, the National Institutes of Health, the Knight Initiative for Alzheimer's Research and the American Health Assistance Foundation supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Health and Medicine:

nachricht Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State

nachricht NTU scientists build new ultrasound device using 3-D printing technology
07.12.2016 | Nanyang Technological University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>