Navigation Links
Innovative screening method identifies possible new treatment for fatal childhood disease
Date:4/18/2011

(NEW YORK, NY, April 15, 2011) Many genes that cause human diseases have parallel genes in other organisms, including yeast. Now Columbia University researchers have used an innovative yeast-based screening method to identify a possible treatment for the fatal childhood disease Niemann-Pick C (NP-C). This "exacerbate-reverse" approach can potentially be used to study any disease. The findings were published online in the Journal of Chemical Biology on April 13, 2011.

NP-C is one of a group of genetic diseases called lipid storage disorders. Lipids are fat-like substances (which include fat and cholesterol) that are in all of the body's cells. With NP-C, an inability to metabolize lipids properly causes dangerous levels of lipids to accumulate in the liver, spleen, and brain. NP-C is an autosomal recessive disorder; that is, both parents must have the defective gene for their child to have the disease. Tragically, a couple may have several children before realizing that they are carriers. Some families have lost three out of four children to the disease.

NP-C is a rare but devastating disease. The symptoms, which usually appear between the ages of four and ten, begin with problems with balance and gait, slurred speech, and developmental delays and inevitably progress to severe cognitive decline, dementia, and, ultimately, death. Frustrated families may spend several years seeking a proper diagnosis, when symptoms are misattributed to learning disabilities or "clumsiness."

Stephen L. Sturley, PhD, associate professor of clinical pediatrics, and Andrew B. Munkacsi, PhD, associate research scientist, both at Columbia University Medical Center, and their colleagues have shown that the existing cancer drug SAHA (developed by Columbia researchers) has the potential to improve three diagnostic criteria of NP-C: accumulation of cholesterol, 2) accumulation of sphingolipids, and 3) defective esterification of LDL-derived cholesterol (esterification is the formation of esters, fatty compounds derived from acids). The discovery of a new use for a drug already on the market is always good news, as the drug has already been tested for safety.

Sturley and his team took advantage of the fact that the gene responsible for 95% of NP-C cases has been present throughout evolution, including in the evolutionarily distant yeast. They used what is called a "synthetic lethality screen" on a yeast model of NC-P. Synthetic lethality occurs when the combination of otherwise insignificant mutations in two or more genes leads to cell death. In other words, they determined which combination of mutations was lethal to the yeast.

The cell nucleus contains proteins called histones. During histone acetylation, a group of atoms called an acetyl group is substituted for a hydrogen atom, and during histone deacetylation, it is removed. When deletion of genes responsible for histone acetylation in the yeast model led to an accumulation of lipids, the researchers hypothesized that an imbalance in histone acetylation caused NP-C disease.

They found that the majority of the 11 histone deacetylase (HDAC) genes were impaired. They then discovered that the cancer drug, an HDAC inhibitor, repaired the genes. Sturley and his team concluded that the genetic pathways that exacerbate lethality in the yeast model could be reversed in human cells, providing a novel treatment for NP-C. In short, using their "exacerbate-reverse" approach, they identified the pathways that exacerbate lethality in their yeast model and then used drugs to manipulate those pathways in the opposite direction.

The next step is to test this new use of the cancer drug on mice and, eventually, hopes Sturley, in clinical trials. Although scientific curiosity originally led Sturley to study NP-C, he is now motivated by the search for a cure. "Once you get to know some of these kids and their families," he says, "it can't be otherwise."

In addition to offering hope to NP-C sufferers and their families, research on NP-C and other lipid storage diseases may help scientists to understand the mechanisms of Alzheimer's disease and other common dementias.


'/>"/>

Contact: Ann Rae Jonas
arj2116@columbia.edu
212-305-3900
Columbia University Medical Center
Source:Eurekalert

Related medicine news :

1. UNC Lineberger scientist receives Innovative Research Grant from Stand Up to Cancer
2. Research team honored for innovative science to advance cancer research
3. Innovative technique gives vision researchers insight into how people recognize faces
4. University Hospitals Case Medical Center testing innovative heat therapy for premature ejaculation
5. Innovative International Healthcare Partnership established at Arizona State University
6. Innovative virtual reality exposure therapy shows promise for returning troops
7. 3rd international conference on innovative approaches in head and neck oncology
8. Cancer prevention expert honored for innovative tobacco research
9. Elsevier launches innovative online radiology board review product
10. UC Davis surgeons test innovative device in patient with swallowing disorder
11. Experts say direct-to-consumer genetic tests need innovative oversight
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/11/2016)... ... February 11, 2016 , ... Student-doctors from Western ... (AOA) Match Program Tuesday, February 9, taking one of the final steps in ... medical education positions across the country. Of the 103 student-doctors who comprise the ...
(Date:2/11/2016)... ... 12, 2016 , ... The Journal of Pain Research has seen ... SJR uses data taken from the Scopus database (Elsevier B.V.) and is a measure ... by the journal over a three year period and also the importance of the ...
(Date:2/11/2016)... ... ... Hall Integrative Health and Chiropractic, PC which focuses on ... in March. All seven practices are set to start accepting patients in March ... According to this 2011 CNN article it is possible: http://www.cnn.com/2011/HEALTH/01/28/reverse.diabetes/ . Current ...
(Date:2/11/2016)... (PRWEB) , ... February 11, 2016 , ... ... upcoming Feb. 23 webinar, “Intel’s Direct-to-Employee Benefit Model: A Case Study for Plans ... Catholic health care system that’s partnering with Intel on value-based health benefits program ...
(Date:2/11/2016)... ... , ... PharmMD CEO Robert Yeager announced today ... contract negotiations, corporate strategy and healthcare data law. Additional responsibilities will include healthcare ... breaches for the Part D Star Rating improvement and Medication Therapy Management firm. ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)... , Feb. 11, 2016 Brain Cancer ... treatment method at West Cancer Center . ... fields to inhibit cancer cell replication causing death of ... than a decade to show a significant extension in ... (GBM) patients. Currently, West Cancer Center is the only ...
(Date:2/11/2016)... , Feb. 11, 2016  AbbVie, a ... AbbVie Rheumatology Scholarship, designed to provide financial support ... as they pursue higher education goals. Fifteen scholars ... the 2016-2017 school year. The AbbVie Rheumatology Scholarship ... Haas , vice president, corporate social responsibility, brand ...
(Date:2/11/2016)... 11, 2016 PLAD, Inc. (OTC Pink: PLAD) is ... sales exceeding company targets, are adding key personnel to ... from the United States Patent and Trademark Office for ... Executive Officer of PLAD, Inc.  In January, PLAD established ... with two new customers, Cumberland Goodwill EMS ...
Breaking Medicine Technology: