Navigation Links
Penn study gives hope for new class of Alzheimer's disease drugs
Date:10/18/2010

PHILADELPHIA Finding a drug that can cross the blood-brain barrier is the bane of drug development for Alzheimer's disease and other neurological disorders of the brain. A new Penn study, published this week in the Journal of Neuroscience, has found and tested in an animal model of Alzheimer's disease a class of drug that is able to enter the brain, where it stabilizes degenerating neurons and improves memory and learning.

In the normal brain, the protein tau plays an important role in stabilizing structures called microtubules in nerve cells, which serve as tracks upon which cellular material is transported. In Alzheimer's disease and related disorders, tau becomes insoluble and forms clumps in the brain. One consequence of these aggregates is a depletion of normal tau, resulting in destabilization of the microtubule tracks that are critical for proper nerve-cell function.

Senior authors Virginia M.-Y. Lee, PhD, director of the Center for Neurodegenerative Disease Research (CNDR), and John Trojanowski, MD, PhD, director of the Institute on Aging and CNDR co-director, introduced the concept of using microtubule-stabilizing drugs over 15 years ago to counteract tangles of tau and compensate for the loss of normal tau function. Kurt Brunden, PhD, director of Drug Discovery at CNDR and Bin Zhang, MD, PhD, senior research investigator, are the first authors on this study from the University of Pennsylvania School of Medicineand the School of Arts and Sciences.

In 2005, the CNDR researchers showed that the anti-cancer drug paclitaxel (Taxol) could improve spinal cord nerve function in mice with tau tangles in their brains, after the drug was absorbed at nerve termini in muscle. "However, paclitaxel and related drugs do not cross the blood-brain barrier" notes Brunden. "So we surveyed a number of additional microtubule-stabilizing agents and discovered that the epothilone class, and in particular epothilone D, readily entered and persisted in the brain."

"The positive effect of epothilone D on the function of axons and on cognition, without the onset of side-effects offers hope that this class of microtubule-stabilizing drugs could progress to testing in Alzheimer patients in the near future," says Lee.

"There are very few tau-focused drugs in clinical trials now for Alzheimer's disease," says Trojanowski. "While we and others have urged that pharmaceutical companies should not put all of their eggs in one drug basket to ensure the highest likelihood of finding disease-modifying therapies for Alzheimer's, we hope this successful mouse study of a tau drug will encourage more pharmaceutical companies to pursue programs on tau-focused drug discovery."

Help from Sponges

The epothilones are microtubule-binding drugs derived from marine sponges and have been used as anti-cancer drugs because they prevent cells from dividing. They do this by keeping microtubules overly stabilized, which blocks cell division and causes cell death in rapidly dividing cells such as cancer cells. However, since nerve cells do not replicate or divide, they are immune to the toxic effects of microtubule-binding drugs.

In Alzheimer's disease and other diseases with tau clumps in the brain, the hope is that a microtubule-stabilizing drug will restore the microtubule tracks to their original supportive structure. This led the researchers to give the tau mice epothilone D (epoD) to replace the now unavailable tau.

Indeed, epothilone D improved the brain function of tau mice, which have tau inclusions in their forebrain, degenerated axons, and broken microtubules. After treating three-month old male tau mice with a low dose of epoD once a week for three months, the mice showed increased numbers of microtubules and improved axon integrity, without notable side effects to organs and immune cells.

What's more, epothilone D reduced deficits in memory and learning in the tau mice. "EpoD improves cognition in mice affected by neurodegenerative tau pathology. These findings suggest that epothilone D and other microtubule-stabilizing agents hold considerable promise as potential treatments for neurodegenerative diseases in humans," says senior author Amos B. Smith III, PhD, the Rhodes Thompson Professor of Chemistry.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. Soy May Reduce Breast Cancer Recurrence: Study
2. Kids Medicaid-Covered Flu Shots Put Docs at a Loss: Study
3. Young Kids Easily Trust What Theyre Told: Study
4. Genomic Systems announces moratorium on studying and treating terminal cancer has ended
5. Study Suggests Osteoporosis Drug Might Treat Loss of Bone in Jaw
6. Study documents wrong-site, wrong-patient procedure errors
7. Study finds a high rate of restless legs syndrome in adults with fibromyalgia
8. Need a study break to refresh? Maybe not, say Stanford researchers
9. National Institutes of Health awards $1.2 million to GSU for collaborative study on discharge decisions at hospitals
10. OCTANE study influences revision of WHO guidelines for treating some HIV-infected women
11. National study shows 1 in 5 children meet criteria for a mental disorder across their lifetime
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Penn study gives hope for new class of Alzheimer's disease drugs
(Date:2/25/2017)... CA (PRWEB) , ... February 25, 2017 , ... FCPX ... ProSharpen Color tools from Pixel Film Studios. With ProSharpen Color users have total control ... to easily refine their color range. With color spectrum tools users can visually see ...
(Date:2/24/2017)... ... 24, 2017 , ... WHAT: , The New Jersey Tech ... well as advocacy for the state and region‘s technology businesses, hosted their 2017 ... Council's Innovation Forecast event highlights innovation throughout the region from small to large ...
(Date:2/24/2017)... ... , ... In the Health Care IT campaign, Robert Herjavec discusses health IT ... you will be attacked, but when.” However, he and many others involved highlight a ... Improvements in auditing and monitoring have taken security in health care a very long ...
(Date:2/24/2017)... ... February 24, 2017 , ... With ProGlass Prism users now have the ability ... total control over position, rotation, distortion, edge softness, edge blur, chromatic aberration, individual glass ... , With ProGlass Prism users are given the tools and effects to generate ...
(Date:2/24/2017)... , ... February 24, 2017 , ... Indiana Fiber Network ... the company later this year. Dyer started as the Chairman of the Management ... the establishment of the corporation including the recruitment of investor/owners and development of the ...
Breaking Medicine News(10 mins):
(Date:2/24/2017)... 24, 2017 Research and Markets has announced the ... Industry Forecast to 2025" report to their offering. ... The Global Empty Capsules Market is poised ... to reach approximately $2.9 billion by 2025. This industry ... on global as well as regional levels presented in the research scope. ...
(Date:2/24/2017)... HARRISBURG, Pa. , Feb. 24, 2017 ... Secretary of Drug and Alcohol Programs Jennifer Smith ... role in providing training for and using naloxone, a ... Mark McCullough , a recovery specialist and overdose ... naloxone by EMS providers. "A significant part ...
(Date:2/24/2017)... Juan Monteverde , founder and managing ... boutique securities firm headquartered at the Empire State Building ... that a class action lawsuit has been filed in the ... Inotek Pharmaceuticals Corporation (NASDAQ:  ITEK)("Inotek" or the "Company") on ... 2015 and December 30, 2016, inclusive (the "Class Period").  ...
Breaking Medicine Technology: