Featured Research

from universities, journals, and other organizations

Potential nutritional therapy for childhood neurodegenerative disease

Date:
August 1, 2013
Source:
University of California, San Diego Health Sciences
Summary:
Researchers have identified the gene mutation responsible for a particularly severe form of pontocerebellar hyplasia, a currently incurable neurodegenerative disease affecting children. Based on results in cultured cells, they are hopeful that a nutritional supplement may one day be able to prevent or reverse the condition.

Healthy brains require a balance of two energy sources -- ATP and GTP -- regulated by the gene AMPD2. A mutation in the gene can result in pontocerebellar hypoplasia, a neurodegenerative disease afflicting children.
Credit: Illustration courtesy of Evgeny Onutchin, Buryat Studio

Researchers at the University of California, San Diego School of Medicine have identified the gene mutation responsible for a particularly severe form of pontocerebellar hypoplasia, a currently incurable neurodegenerative disease affecting children. Based on results in cultured cells, they are hopeful that a nutritional supplement may one day be able to prevent or reverse the condition.

Related Articles


The study, from a team of international collaborators led by Joseph G. Gleeson, MD -- Howard Hughes Medical Institute investigator and professor in the UCSD Departments of Neurosciences and Pediatrics and at Rady Children's Hospital-San Diego, a research affiliate of UC San Diego -- will be published in the August 1 issue of the journal Cell.

Pontocerebellar hypoplasia is a group of rare, related genetic neurological disorders characterized by abnormal development of the brain, resulting in disabilities in movement and cognitive function. Most patients do not survive to adulthood.

Gleeson and colleagues identified a specific gene mutation that causes pontocerebellar hypoplasia and linked it to an inability of brain cells to generate a form of energy required to synthesize proteins. Without this ability, neurons die, but the researchers also found that bypassing this block with a nutritional supplement restored neuronal survival.

"The goal is to one day use this supplement to prevent or reverse the course of neurodegeneration in humans, and thus cure this disease," said Gleeson.

Nucleotides are the main energy source of cells. They exist in two forms: ATP and GTP. While ATP fuels most energy requirements, GTP is the source for protein synthesis. Mutations in the gene AMPD2 lead to the accumulation of ATP, and the subsequent depletion of GTP. The result, said Gleeson, is an imbalance in the cell's energy source, which prevents protein synthesis and causes neurodegeneration.

"These patients have what is described in medical textbooks as an untreatable disease, yet show mutations in a neuronal pathway that should be amenable to medication," said study co-author Naiara Akizu, PhD, a member of Gleeson's lab. "We chose to bypass this block using AICAR, a substance known to improve exercise endurance."

The researchers tested their AICAR-based treatment in genetic models of the disease and in human cells. The next step, said Gleeson, will be to test AICAR in a mouse model of pontocerebellar hypoplasia that his lab has created, followed by human trials.

"We don't know if AICAR will work in mice or humans yet, but our work in cells definitely points in that direction," said co-author Vincent Cantagrel, PhD. "This rare disorder might be one of the first treatable neurodegenerative diseases in humans."

Other co-authors include Jana Schroth, Na Cai, Keith Vaux, Ali G. Fenstermaker, Jennifer L. Silhavy, Emily Spencer, Rasim Ozgur Rosti, Eric Scott, Douglas McCloskey, Robert K. Naviaux, Jeremy Van Vleet, UCSD Departments of Neurosiences, Bioengineering, Medicine, Pediatrics, Pathology and Glycotechnology Core Resource; Edward W. Holmes, Sanford Consortium for Regenerative Medicine; Judith S. Scheliga Sanford-Burnham Medical Research Institute; Keiko Toyama, Hiroko Morisaki and Takayuki Morisaki, Osaka University; Fatma Mujgan Sonmez and Figen Celep, Turgut Ozal University and Karadeniz Technical University, Turkey; Azza Oraby and Maha S. Zaki, Cairo University Children's Hospital, and National Research Center, Egypt; Raidah Al-Baradie, Eissa Faqeih and Mohammed Saleh, King Fahd Specialist Hospital and Children's Hospital, Kingdom of Saudi Arabia; Elizabeth Nickerson and Stacey Gabriel, The Broad Institute of MIT and Harvard University.

Funding for this research came, in part, from the National Institutes of Health (grants HD070494, NS048453), the Howard Hughes Medical Institute, California Institute for Regenerative Medicine, UCSD Christini Fund, Jane Botsford Johnson Foundation, Broad Institute, Center for Inherited Disease Research and Simons Foundation Autism Research Initiative.


Story Source:

The above story is based on materials provided by University of California, San Diego Health Sciences. The original article was written by Scott LaFee. Note: Materials may be edited for content and length.


Journal Reference:

  1. Naiara Akizu, Vincent Cantagrel, Jana Schroth, Na Cai, Keith Vaux, Douglas McCloskey, RobertK. Naviaux, Jeremy VanVleet, AliG. Fenstermaker, JenniferL. Silhavy, JudithS. Scheliga, Keiko Toyama, Hiroko Morisaki, Fatma M. Sonmez, Figen Celep, Azza Oraby, MahaS. Zaki, Raidah Al-Baradie, Eissa A. Faqeih, Mohammed A.M. Saleh, Emily Spencer, RasimOzgur Rosti, Eric Scott, Elizabeth Nickerson, Stacey Gabriel, Takayuki Morisaki, EdwardW. Holmes, JosephG. Gleeson. AMPD2 Regulates GTP Synthesis and Is Mutated in a Potentially Treatable Neurodegenerative Brainstem Disorder. Cell, 2013; 154 (3): 505 DOI: 10.1016/j.cell.2013.07.005

Cite This Page:

University of California, San Diego Health Sciences. "Potential nutritional therapy for childhood neurodegenerative disease." ScienceDaily. ScienceDaily, 1 August 2013. <www.sciencedaily.com/releases/2013/08/130801125028.htm>.
University of California, San Diego Health Sciences. (2013, August 1). Potential nutritional therapy for childhood neurodegenerative disease. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2013/08/130801125028.htm
University of California, San Diego Health Sciences. "Potential nutritional therapy for childhood neurodegenerative disease." ScienceDaily. www.sciencedaily.com/releases/2013/08/130801125028.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Why Your Boss Should Let You Sleep In

Why Your Boss Should Let You Sleep In

Newsy (Dec. 17, 2014) According to research out of the University of Pennsylvania, waking up for work is the biggest factor that causes Americans to lose sleep. Video provided by Newsy
Powered by NewsLook.com
Flu Outbreak Closing Schools in Ohio

Flu Outbreak Closing Schools in Ohio

AP (Dec. 17, 2014) A wave of flu illnesses has forced some Ohio schools to shut down over the past week. State officials confirmed one pediatric flu-related death, a 15-year-old girl in southern Ohio. (Dec. 17) 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:

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