Featured Research

from universities, journals, and other organizations

Test Quickly Assesses Whether Alzheimer's Drugs Are Hitting Their Target

Date:
April 15, 2009
Source:
Washington University in St. Louis
Summary:
A test developed by physician-scientists may help quickly asses whether certain Alzheimer's drugs are hitting their target.

A test developed by physician-scientists at Washington University School of Medicine in St. Louis may help assess more quickly the ability of Alzheimer's drugs to affect one of the possible underlying causes of Alzheimer's disease in humans, accelerating the development of new treatments.

Related Articles


Scientists used the test to show that an Alzheimer's drug given to healthy volunteers reduced production of a substance known as amyloid beta (A-beta), a normal byproduct of human metabolism that builds to unhealthy levels forming brain plaques in Alzheimer's patients. The drug candidate, LY450139, which is also known as semagacestat, is being studied in clinical trials by Eli Lilly and Company.

Ongoing clinical trials are studying the effect that semagacestat may have on cognitive function and biochemical and brain imaging biomarkers in patients with Alzheimer's disease. Washington University researchers wanted to see whether the new measurement technique, stable isotope-linked kinetics (SILK), could detect the study drug's impact on A-beta synthesis in healthy volunteers.

"Bringing an Alzheimer's disease drug into clinical trials from tests in animal models has always been challenging," says study director Randall Bateman, M.D., a Washington University neurologist who treats patients at Barnes-Jewish Hospital. "We haven't had a way to quickly and accurately assess a drug's effects, and that meant there always had to be some degree of educated guesswork when it came to setting the optimal dosage for humans. SILK may help to eliminate much of that guesswork."

Scientists are unsure whether increased A-beta production, reduced clearance or a combination of the two lead to the A-beta buildup in the brain, a process that many believe triggers Alzheimer's disease. Bateman and his colleagues are currently using SILK to try to answer this question.

Until SILK, there has not been a way to directly measure the production or clearance of A-beta. The efficacy of potential new Alzheimer's drug candidates has been assessed by monitoring the cognitive functions of patients with the disease for extended periods of time, which require large, lengthy and expensive studies.

In their double-blind study, scientists gave 20 healthy volunteers varying doses of either a study drug or a placebo. At the start of the SILK test, volunteers were connected to an intravenous drip that gave them a slightly altered form of the amino acid leucine, which is a component of A-beta.

Over the course of several hours, cells in the brain picked up the labeled leucine and incorporated it into the new copies made of A-beta and other proteins. The scientists took periodic samples of the subjects' cerebrospinal fluid to determine how much of the A-beta included altered leucine.

Tracking the rise of the percentage of labeled A-beta over time reveals the A-beta production rate. Scientists then stop the leucine labeling but continue analyzing spinal fluid samples. As the body removed old A-beta and made new A-beta, the percentage of A-beta containing altered leucine dropped, revealing the A-beta clearance rate.

The results suggest a dose-dependent drop in A-beta production, with an 84 percent reduction in A-beta production being measured with the highest study drug dose.

The SILK procedure takes 36 hours, but provides scientists a more detailed assessment of amyloid beta production and clearance levels than they can obtain through conventional methods.

"You could use a spinal tap to look directly at the amount of A-beta present in the cerebrospinal fluid, but we've shown that natural processes cause A-beta levels to change dynamically," says Bateman. "Such changes make it more difficult to assess the effects of a drug in that fashion."

The study was funded through a Lilly grant from a funding program that allowed Bateman to propose the research and retain control of it. Five of the paper's 12 authors are Eli Lilly employees.

Washington University in St. Louis licensed its pending patents on SILK to C2N Diagnostics, LLC, a St. Louis diagnostics company started by Bateman and senior author David Holtzman, M.D., the Andrew and Gretchen Jones Professor and Chair of Neurology. Bateman and Holtzman's financial interests in the company are governed by the university's conflict-of-interest policies.

Funding from Eli Lilly and Company supported this research.


Story Source:

The above story is based on materials provided by Washington University in St. Louis. Note: Materials may be edited for content and length.


Journal Reference:

  1. Bateman RJ, Siemers E, Mawuenyega KG, Wen G, Bronwing KR, Sigurdson, WC, Yarasheski KE, Friedrich SW, DeMattos RB, May PC, Paul SM, Holtzman DM. A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system. Annals of Neurology, Online April 10, 2009

Cite This Page:

Washington University in St. Louis. "Test Quickly Assesses Whether Alzheimer's Drugs Are Hitting Their Target." ScienceDaily. ScienceDaily, 15 April 2009. <www.sciencedaily.com/releases/2009/04/090410075108.htm>.
Washington University in St. Louis. (2009, April 15). Test Quickly Assesses Whether Alzheimer's Drugs Are Hitting Their Target. ScienceDaily. Retrieved February 26, 2015 from www.sciencedaily.com/releases/2009/04/090410075108.htm
Washington University in St. Louis. "Test Quickly Assesses Whether Alzheimer's Drugs Are Hitting Their Target." ScienceDaily. www.sciencedaily.com/releases/2009/04/090410075108.htm (accessed February 26, 2015).

Share This


More From ScienceDaily



More Mind & Brain News

Thursday, February 26, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sleeping Too Much Or Too Little Might Increase Stroke Risk

Sleeping Too Much Or Too Little Might Increase Stroke Risk

Newsy (Feb. 26, 2015) People who sleep more than eight hours per night are 45 percent more likely to have a stroke, according to a University of Cambridge study. Video provided by Newsy
Powered by NewsLook.com
Mayor Says District of Columbia to Go Ahead With Pot Legalization

Mayor Says District of Columbia to Go Ahead With Pot Legalization

Reuters - News Video Online (Feb. 25, 2015) Washington&apos;s mayor says the District of Columbia will move forward with marijuana legalization, despite pushback from Congress. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Marijuana Nowhere Near As Deadly As Alcohol: Study

Marijuana Nowhere Near As Deadly As Alcohol: Study

Newsy (Feb. 25, 2015) A new study says marijuana is about 114 times less deadly than alcohol. Video provided by Newsy
Powered by NewsLook.com
Researchers Replace Damaged Hands With Prostheses

Researchers Replace Damaged Hands With Prostheses

Newsy (Feb. 25, 2015) Scientists in Austria have been able to fit patients who&apos;ve lost the use of a hand with bionic prostheses the patients control with their minds. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins