Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Potential new drug candidate found for Alzheimer's disease

01.06.2011
Researchers at the University of California, San Diego, the Medical University of South Carolina and American Life Science Pharmaceuticals of San Diego have demonstrated that oral administration of a cysteine protease inhibitor, E64d, not only reduces the build-up of â-amyloid (Aâ) in the brains of animal models for Alzheimer's disease, but also results in a substantial improvement in memory deficit.

A paper detailing the findings has been published as an early online version and is scheduled for publication in the September 6 issue of the Journal of Alzheimer's Disease.

According to lead investigator Vivian Y. H. Hook, PhD, professor of the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of neurosciences, pharmacology and medicine at the UCSD School of Medicine, this is major news for scientists studying Alzheimer's disease.

"The finding is especially exciting because E64d has previously been shown safe for use in humans, so we believe the compound has strong potential as a new therapy for Alzheimer's disease," said Hook.

Increased Aâ levels in the brain are associated with the development of memory loss and amyloid plaque, the hallmark of Alzheimer's disease. Aâ peptides are "cut" out from a larger protein called the amyloid precursor protein (APP) by an enzymatic "scissor" called â-secretase, and aggregate to form plaques in the brain regions responsible for memory.

E64d reduces Aâ by inhibiting the â-secretase "scissors" from "cutting" the APP chain into smaller toxic Aâ peptides. But in this study, the researchers found that the compound actually increases the activity of a protease called BACE1 which, to date, has been regarded as the primary â-secretase. Instead, E64d appears to lower brain Aâ by inhibiting the â-secretase activity of another protease, Cathepsin B.

"The study indicates Cathepsin B as a new target for therapeutic inhibition of Aâ production and subsequent improved memory function," said Hook. "This is an important finding because we show that â-secretase inhibition can occur with Cathepsin B inhibition and without BACE1 inhibition."

The researchers studied both old and young transgenic Alzheimer's disease mice, and found that memory loss improved in both. In young mice, feeding E64d prevented development of memory loss; in old mice with memory loss, it improved memory.

The study builds upon work published in March 2008 that first demonstrated that inhibitors of Cathepsin B resulted in improved memory and reduction of Aâ and amyloid plaque; but in that study, the drug was administered directly into the brains of AD mice. In the new study, oral administration of the drug was efficacious and could lead the way to clinical trials in humans.

Co-authors of the study were Gregory Hook, PhD, of American Life Science Pharmaceuticals in San Diego, and Mark Kindy of the Medical University of South Carolina, as well as the Ralph H. Johnson VA Medical Center, and Applied Neurotechnology, Inc., in Charleston, SD.

G. Hook is an employee and has equity in American Life Science Pharmaceuticals (ALSP); V. Hook is chair of ALSP's scientific advisory board and holds equity in the company, and Kindy holds equity in Applied Neurotechnology, relationships disclosed to their institutions.

The study was supported in part by the National Institute on Aging of the National Institutes of Health and the Alzheimer's Drug Development Foundation.

Debra Kain | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht New gene catalog of ocean microbiome reveals surprises
18.08.2017 | University of Hawaii at Manoa

nachricht Organ Crosstalk: Fatty Liver Can Cause Damage to Other Organs
18.08.2017 | Deutsches Zentrum für Diabetesforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New gene catalog of ocean microbiome reveals surprises

18.08.2017 | Life Sciences

Astrophysicists explain the mysterious behavior of cosmic rays

18.08.2017 | Physics and Astronomy

AI implications: Engineer's model lays groundwork for machine-learning device

18.08.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>