Featured Research

from universities, journals, and other organizations

New marker found for Sanfilippo disease

Date:
March 1, 2011
Source:
University of California - San Diego
Summary:
Researchers have described the build-up of a novel secondary metabolite in Sanfilippo disease, a discovery that could improve understanding of the pathology of Sanfillippo disease and refine diagnostic techniques.

Sanfilippo disease is a rare disorder caused by the failure of enzymes to break down specific kinds of complex carbohydrates, resulting in their accumulation in cells and often severe physical and neurological problems -- and sometimes early death.

In a paper published in the March 4 issue of the Journal of Biological Chemistry, researchers at the University of California, San Diego School of Medicine, led by Jeffrey D. Esko, PhD, professor in the Department of Cellular and Molecular Medicine, describe the build-up of a novel secondary metabolite in Sanfilippo disease, a discovery that could improve understanding of the disease's pathology and refine diagnostic techniques.

Sanfilippo is one of a group of genetically inherited metabolic disorders called mucopolysaccharidoses, all of which involve the inability of different lysosomal enzymes to catabolize or break down glycosaminoglycans -- complex sugar carbohydrates that help cells build skin, bone, cartilage, tendons and connective tissues.

"It's a very ordered sequence of degradation," said Esko, co-director of the Glycobiology Research and Training Center at UC San Diego. "Interference with any of the steps in the enzymatic process results in an accumulation of metabolites, which causes lyosomal dysfunction. Cells become constipated, leading to internal changes and dysfunction."

For patients with severe mucopolysaccharidosis, the consequences can be catastrophic. As incompletely degraded glycosaminoglycans accumulate in cells and tissues, they cause permanent, progressive damage that affects appearance, physical abilities, organ function and, most profoundly, mental development. Children with the disease can experience severe neuropathology and significant early mortality. It's estimated that 1 in 25,000 children in the United States have one of several forms of the disease. Some mucopolysaccharidoses can be temporarily treated with enzyme replacement therapies, but the body's blood-brain barrier blocks neurological benefit. There is no current cure.

"The three approved drugs on the market mask the genetic defect by supplementing the missing enzymes," said Esko. "They can help resolve storage in many organs, but not the brain because the enzymes do not cross the barrier. And they are very, very expensive."

In the new research, Esko and colleague William C. Lamanna, PhD, studied enzymatic activity in Sanfilippo patient fibroblasts, a type of cell most commonly found in connective tissues. They noted that defective enzymatic activity resulted in the accumulation of not just a glycosaminoglycan called heparan sulfate, but also a secondary metabolite called dermatan sulfate. Sanfilippo cells had levels of dermatan sulfate two- to five-fold higher than normal.

The combined accumulation of heparan sulfate with dermatan sulfate, researchers said, may explain some of the distinct pathological features of Sanfilippo disease. The emergence of dermatan sulfate as an additional biomarker for Sanfilippo disease could be useful in detection and diagnosis, though Esko said studies using patient tissue biopsies or blood or urine samples remain to be conducted.

"Right now, this discovery probably won't change the current therapy for Sanfilippo" said Lamanna, "but it does improve what we know about how the disease works and how to diagnose it."

The work follows related research published in 2010 in Molecular Therapy by Esko, Yitzhak Tor, PhD, UCSD Department of Chemistry and Biochemistry and Moores Cancer Center and colleagues that described a new type of targeting process for delivering modified enzymes to cells.

Co-authors of the JBC paper are Roger Lawrence and Stephane Sarrazin, both from the UCSD Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center.


Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.


Journal Reference:

  1. W. C. Lamanna, R. Lawrence, S. Sarrazin, J. D. Esko. Secondary Storage of Dermatan Sulfate in Sanfilippo Disease. Journal of Biological Chemistry, 2010; 286 (9): 6955 DOI: 10.1074/jbc.M110.192062

Cite This Page:

University of California - San Diego. "New marker found for Sanfilippo disease." ScienceDaily. ScienceDaily, 1 March 2011. <www.sciencedaily.com/releases/2011/02/110228151903.htm>.
University of California - San Diego. (2011, March 1). New marker found for Sanfilippo disease. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2011/02/110228151903.htm
University of California - San Diego. "New marker found for Sanfilippo disease." ScienceDaily. www.sciencedaily.com/releases/2011/02/110228151903.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Microneedle Patch Promises Painless Pricks

Microneedle Patch Promises Painless Pricks

Reuters - Innovations Video Online (Oct. 18, 2014) Researchers at The National University of Singapore have invented a new microneedle patch that could offer a faster and less painful delivery of drugs such as insulin and painkillers. Video provided by Reuters
Powered by NewsLook.com
Raw: Nurse Nina Pham Arrives in Maryland

Raw: Nurse Nina Pham Arrives in Maryland

AP (Oct. 17, 2014) The first nurse to be diagnosed with Ebola at a Dallas hospital walked down the stairs of an executive jet into an ambulance at an airport in Frederick, Maryland, on Thursday. Pham will be treated at the National Institutes of Health. (Oct. 16) Video provided by AP
Powered by NewsLook.com
Raw: Cruise Ship Returns to US Over Ebola Fears

Raw: Cruise Ship Returns to US Over Ebola Fears

AP (Oct. 17, 2014) A Caribbean cruise ship carrying a Dallas health care worker who is being monitored for signs of the Ebola virus is heading back to Texas, US, after being refused permission to dock in Cozumel, Mexico. (Oct. 17) Video provided by AP
Powered by NewsLook.com
Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

AFP (Oct. 17, 2014) All four suspected Ebola cases admitted to hospitals in Spain on Thursday have tested negative for the deadly virus in a first round of tests, the government said Friday. Duration: 00:55 Video provided by AFP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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