Featured Research

from universities, journals, and other organizations

Compound blocks brain cell destruction in Parkinson's disease; Findings may open door to first protective therapy

Date:
February 12, 2011
Source:
Scripps Research Institute
Summary:
Scientists have produced the first known compound to show significant effectiveness in protecting brain cells directly affected by Parkinson's disease, a progressive and fatal neurodegenerative disorder.

Scientists from the Florida campus of The Scripps Research Institute have produced the first known compound to show significant effectiveness in protecting brain cells directly affected by Parkinson's disease, a progressive and fatal neurodegenerative disorder.

Although the findings were in animal models of the disease, the effectiveness of the compound, combined with its potential to be taken orally, offers the tantalizing possibility of a potentially useful future therapy for Parkinson's disease patients. The results were published in two separate studies in the journal ACS Chemical Neuroscience.

"These studies present compelling data on the first oral, brain-penetrating inhibitor to show significant efficacy in preventing neurodegeneration in both mouse and rat models of Parkinson's disease," said team leader Philip LoGrasso, a professor in the Department of Molecular Therapeutics and senior director for drug discovery at Scripps Florida. "The compound offers one of the best opportunities we have for the development of an effective neuroprotective treatment."

The new small molecule -- labeled SR-3306 -- is aimed at inhibiting a class of enzymes called c-jun-N-terminal kinases (JNK). Pronounced "junk," these enzymes have been shown to play an important role in neuron (nerve cell) survival. As such, they have become a highly viable target for drugs to treat neurodegenerative disorders such as Parkinson's disease.

"A drug like SR-3306 that prevents neurodegeneration would be a quantum leap in the clinical treatment of Parkinson's because all current therapies treat only the symptoms of the disease, not the underlying pathologies," LoGrasso said.

Patients with Parkinson's disease suffer from the loss of a group of neurons in the substantia nigra pars compacta (SNpc), part of the midbrain involved in motor control. These cells produce dopamine, a neurotransmitter that plays a key role in motor reflexes and cognition. The disease also affects projecting nerve fibers in the striatum, a part of the forebrain filled with cells that interact with dopamine. Stopping the Progression of Neuron Destruction in Animal Models

The SR-3306 compound, which has been in development at Scripps Florida for several years, performed well in both cell culture and animal models. In cell culture, the compound showed greater than 90 percent protection against induced cell death of primary dopaminergic neurons, while in mouse models of induced neuron death, the compound showed protective levels of approximately 72 percent.

The scientists went one step further, testing the new compound in a rat model, which duplicates the physical symptoms often seen with the human disease -- a pronounced and progressive loss of motor skills. The results showed SR-3306 provided a protection level of approximately 30 percent in the brain, a level that reduced the dysfunctional motor responses by nearly 90 percent.

"It was a surprise that level of neuroprotection reduced the behavioral impact so strongly," LoGrasso said, "but it's indicative of how it might perform in human patients. While SR-3306 doesn't represent a cure, it does appear to have the potential of stopping the progression of the disease."

The new studies are part of a $7.6 million multiyear grant awarded to LoGrasso in 2008 by the National Institutes of Neurological Disorders and Stroke (NINDS). The grant will enable Scripps Research and potential partners to file an application for an investigational new drug (IND) -- the first step in the lengthy clinical trials process required by the U.S. Food and Drug Administration before a new drug can be brought to market.

The first authors of the study, "Small Molecule c-jun-N-terminal Kinase (JNK) Inhibitors Protect Dopaminergic Neurons in a Model of Parkinson's Disease," are Jeremy W. Chambers and Alok Pachori of Scripps Research. Other authors include Shannon Howard, Michelle Ganno, Donald Hansen Jr., Ted Kamenecka, Xinyi Song, Derek Duckett, Weimin Chen, Yuan Yuan Ling, Lisa Cherry, Michael D. Cameron, Li Lin, and Claudia H. Ruiz, also of Scripps Research.

The first author of the study, "JNK Inhibition Protects Dopamine Neurons and Provides Behavioral Improvement in a Rat 6-hydroxydopamine Model of Parkinson's Disease," is Candice E. Crocker of Dalhousie University, Halifax, Nova Scotia, Canada. Other authors include Susan Khan and Michael D. Cameron of Scripps Research, and Harold A. Robertson and George S. Robertson of Dalhousie.

Both studies were supported by the National Institutes of Health. Harold A. Robertson and George S. Robertson were supported by funding from the Atlantic Innovation Fund.


Story Source:

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


Journal References:

  1. Jeremy W. Chambers, Alok Pachori, Shannon Howard, Michelle Ganno, Donald Hansen, Ted Kamenecka, Xinyi Song, Derek Duckett, Weimin Chen, Yuan Yuan Ling, Lisa Cherry, Michael D. Cameron, Li Lin, Claudia H. Ruiz, Philip LoGrasso. Small Molecule c-jun-N-Terminal Kinase Inhibitors Protect Dopaminergic Neurons in a Model of Parkinson’s Disease. ACS Chemical Neuroscience, 2011; 110207090626012 DOI: 10.1021/cn100109k
  2. Candice E. Crocker, Susan Khan, Michael D. Cameron, Harold A. Robertson, George S. Robertson, Philip LoGrasso. JNK Inhibition Protects Dopamine Neurons and Provides Behavioral Improvement in a Rat 6-Hydroxydopamine Model of Parkinson’s Disease. ACS Chemical Neuroscience, 2011; DOI: 10.1021/cn1001107

Cite This Page:

Scripps Research Institute. "Compound blocks brain cell destruction in Parkinson's disease; Findings may open door to first protective therapy." ScienceDaily. ScienceDaily, 12 February 2011. <www.sciencedaily.com/releases/2011/02/110211153923.htm>.
Scripps Research Institute. (2011, February 12). Compound blocks brain cell destruction in Parkinson's disease; Findings may open door to first protective therapy. ScienceDaily. Retrieved September 21, 2014 from www.sciencedaily.com/releases/2011/02/110211153923.htm
Scripps Research Institute. "Compound blocks brain cell destruction in Parkinson's disease; Findings may open door to first protective therapy." ScienceDaily. www.sciencedaily.com/releases/2011/02/110211153923.htm (accessed September 21, 2014).

Share This



More Health & Medicine News

Sunday, September 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
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
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) 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