Featured Research

from universities, journals, and other organizations

Novel drug alleviates symptoms in Huntington's and Alzheimer's mice

Date:
June 3, 2011
Source:
Gladstone Institutes
Summary:
Scientists have identified a drug candidate that diminishes the effects of both Alzheimer's disease and Huntington's disease in animal models, offering new hope for patients who currently lack any medications to halt the progression of these two debilitating illnesses.

Scientists at the Gladstone Institutes have identified a drug candidate that diminishes the effects of both Alzheimer's disease and Huntington's disease in animal models, offering new hope for patients who currently lack any medications to halt the progression of these two debilitating illnesses.

Gladstone Investigator Paul Muchowski, PhD, has identified a new compound called JM6 in experiments done in collaboration with an international team of researchers, and which are being published June 2 in an online article in Cell. In laboratory tests involving mice genetically engineered to model one or the other of the two diseases, Dr. Muchowski's team found that JM6 blocks kynurenine 3-monooxygenase (KMO), an enzyme that has long been speculated to play a role in neurodegenerative diseases.

In mice modeling Alzheimer's disease, the novel compound prevented memory deficits and the loss of synaptic connections between brain cells -- both of which are key features of the human disease. In mice modeling Huntington's disease, JM6 prevented brain inflammation and the loss of synaptic connections between brain cells, while also extending lifespan.

The need for a therapeutic breakthrough for diseases that degrade the brain over time is great. Alzheimer's disease -- the most common form of dementia -- afflicts an estimated 5.4 million people in the United States alone, at an annual cost of $183 billion, according to the Alzheimer's Association. Without a therapeutic breakthrough, the number of Americans with Alzheimer's disease is expected to double by 2050, as a new case will develop every 33 seconds. Huntington's disease, meanwhile, is the most common inherited neurodegenerative brain disorder, diminishing the ability of some 30,000 Americans to walk, talk and reason.

"This discovery has significant implications for two devastating diseases and suggests that the KMO enzyme is a good protein for us to target with medications in diverse neurodegenerative disorders," said Lennart Mucke, MD, who oversees all neurological research at Gladstone and who won the Potamkin Prize last year for developing experimental strategies to make the brain more resistant to Alzheimer's. "With any luck, Dr. Muchowski and his colleagues could begin testing this drug in patients within the next two years."

Remarkably, JM6 does not penetrate into the brain, but works by inhibiting KMO in the blood. The blood cells then send a protective signal to the brain, to stabilize brain-cell function and prevent neurodegeneration. The fact that the compound does not pass the so-called blood-brain barrier will facilitate testing in patients, as JM6's potential impact could be confirmed with a simple blood test.

JM6 was named for Dr. Muchowski's father, Dr. Joseph Muchowski, Ph.D., a retired medicinal chemist who helped his son devise the novel KMO inhibitor. The study was carried out in collaboration with the laboratories of Dr. Robert Schwarcz, a University of Maryland School of Medicine professor who pioneered studies linking KMO and metabolically related enzymes to nerve-cell loss, and Professor Eliezer Masliah at the University of California, San Diego, an expert in neuropathology.

These findings are further bolstered by research also being published online June 2 in Current Biology. Led by Flaviano Giorgini, PhD, of the University of Leicester -- and a former postdoc of Dr. Muchowski's -- the other study provides compelling genetic and pharmacological evidence of KMO's importance in fruit flies genetically modified to mimic Huntington's disease.

"In a world where there is such vacuum of hope about Huntington's disease, I am thrilled that someone of Dr. Muchowski's caliber has suggested the possibility of imminent clinical trials," said Charles Sabine, a former NBC correspondent who watched Huntington's disease kill his father. Both Mr. Sabine and his brother currently have Huntington's. "I believe that families with Huntington's disease should jump at the opportunity of being involved in those trials."

Gladstone, together with the University of Maryland School of Medicine, is currently considering a variety of ways to get JM6 into Phase 1 safety trials in humans -- hopefully sometime in 2013 -- including the spinout of a venture-capital-backed startup or collaboration with a large pharmaceutical company. Gladstone also has a grant application pending with the National Institute of Neurological Disorders and Stroke to help fund safety tests required for initiating human trials. Gladstone, the National Institutes of Health and the Taube-Koret Center for Huntington's Disease Research at Gladstone all provided funding for this study.

Dr. Paul Muchowski, an associate investigator at Gladstone, specializes in neurodegenerative diseases. He is also an associate professor in the Departments of Biochemistry and Biophysics, and Neurology, at the University of California, San Francisco (UCSF).


Story Source:

The above story is based on materials provided by Gladstone Institutes. Note: Materials may be edited for content and length.


Journal Reference:

  1. Daniel Zwilling, Shao-Yi Huang, Korrapati V. Sathyasaikumar, Francesca M. Notarangelo, Paolo Guidetti, Hui-Qiu Wu, Jason Lee, Jennifer Truong, Yaisa Andrews-Zwilling, Eric W. Hsieh, Jamie Y. Louie, Tiffany Wu, Kimberly Scearce-Levie, Christina Patrick, Anthony Adame, Flaviano Giorgini, Saliha Moussaoui, Grit Laue, Arash Rassoulpour, Gunnar Flik, Yadong Huang, Joseph M. Muchowski, Eliezer Masliah, Robert Schwarcz, Paul J. Muchowski. Kynurenine 3-Monooxygenase Inhibition in Blood Ameliorates Neurodegeneration. Cell, 02 June 2011 DOI: 10.1016/j.cell.2011.05.020

Cite This Page:

Gladstone Institutes. "Novel drug alleviates symptoms in Huntington's and Alzheimer's mice." ScienceDaily. ScienceDaily, 3 June 2011. <www.sciencedaily.com/releases/2011/06/110602122250.htm>.
Gladstone Institutes. (2011, June 3). Novel drug alleviates symptoms in Huntington's and Alzheimer's mice. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2011/06/110602122250.htm
Gladstone Institutes. "Novel drug alleviates symptoms in Huntington's and Alzheimer's mice." ScienceDaily. www.sciencedaily.com/releases/2011/06/110602122250.htm (accessed September 20, 2014).

Share This



More Mind & Brain News

Saturday, September 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Food Addiction Might Be Caused By PTSD

Food Addiction Might Be Caused By PTSD

Newsy (Sep. 18, 2014) New research shows that women who suffer from PTSD are three times more likely to develop a food addiction. Video provided by Newsy
Powered by NewsLook.com
Corporal Punishment on Decline, Debate Renews

Corporal Punishment on Decline, Debate Renews

AP (Sep. 16, 2014) Corporal punishment in the United States is on the decline, but there is renewed debate over its use after Minnesota Vikings running back Adrian Peterson was charged with child abuse. (Sept. 16) Video provided by AP
Powered by NewsLook.com
FDA Eyes Skin Shocks Used at Mass. School

FDA Eyes Skin Shocks Used at Mass. School

AP (Sep. 15, 2014) The FDA is considering whether to ban devices used by the Judge Rotenberg Educational Center in Canton, Massachusetts, the only place in the country known to use electrical skin shocks as aversive conditioning for aggressive patients. (Sept. 15) Video provided by AP
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:
from the past week

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