Featured Research

from universities, journals, and other organizations

Rare Genetic Disease Successfully Reversed Using Stem Cell Transplantation

Date:
September 18, 2009
Source:
Scripps Research Institute
Summary:
A recent study offers good news for families of children afflicted with the rare genetic disorder, cystinosis. In research that holds out hope for one day developing a potential therapy to treat the fatal disorder, the study shows that the genetic defect in mice can be corrected with stem cell transplantation.

A recent study by Scripps Research Institute scientists offers good news for families of children afflicted with the rare genetic disorder, cystinosis. In research that holds out hope for one day developing a potential therapy to treat the fatal disorder, the study shows that the genetic defect in mice can be corrected with stem cell transplantation.

Related Articles


"After meeting the children who suffer from this disease, like an 18-year-old who has already had three kidney transplants, and the families who are desperately searching for help, our team is committed to moving toward a cure for cystinosis, a lysosomal storage disorder," says principal investigator Stephanie Cherqui, assistant professor in the Department of Molecular and Experimental Medicine. "This study is an important step toward that goal."

In the study, which is published in the September 17, 2009 print edition of the journal Blood, the Scripps Research team used bone marrow stem cell transplantation to address symptoms of cystinosis in a mouse model. The procedure virtually halted the cystine accumulation responsible for the disease and the cascade of cell death that follows.

Cystine is a byproduct of the break down of cellular components the body no longer needs in the cell's "housekeeping" organelles, called lysosomes. Normally, cystine is shunted out of cells, but in cystinosis a gene defect of the lysosomal cystine transporter causes it to build up, forming crystals that are especially damaging to the kidneys and eyes.

A Rare But Devastating Disease

While cystinosis is rare—affecting an estimated 500 people in the United States and 2,000 worldwide—it is devastating. Three types of cystinosis have been described based on the age at diagnosis and the amount of cystine in cells: infantile onset, adolescent onset, and adult onset. Children as young as six months can begin to suffer renal dysfunction, which grows progressively worse with time. Other symptoms include diabetes, muscular disease, neurological dysfunction, and retinopathy. Infantile onset is the most common, as well as the most severe, form of the disease.

The only available drug to treat cystinosis, cysteamine, while slowing the progression of kidney degradation, does not prevent it, and end-stage kidney failure is inevitable.

"Cysteamine must be given every six hours, so children have to be woken up each night to take this drug, which has unpleasant side effects, and many others to treat various symptoms," Cherqui says. "So although there is treatment, it is difficult treatment that does not cure the disease."

"Surprised and Encouraged"

In the new study, the researchers found that transplanted bone marrow stem cells carrying the normal lysosomal cystine transporter gene abundantly engrafted into every tissue of the experimental mice. This led to an average drop in cystine levels of about 80 percent in every organ. In addition to preventing kidney dysfunction, there was less deposition of cystine crystals in the cornea, less bone demineralization, and an improvement in motor function.

"The results really surprised and encouraged us," says Cherqui, who as a doctoral student in France in 1998 helped discover the gene involved in cystinosis. "Because the defect is present in every cell of the body, we did not expect a bone marrow stem cell transplant to be so widespread and effective."

Cherqui, who generated the mouse model in 2000 that is currently used to study cystinosis, says that adult bone marrow stem cell therapy is particularly well suited as a potential treatment for cystinosis because these cells target all types of tissues. In addition, stem cells reside in the bone marrow for the duration of a patient's life, becoming active as needed, a particular benefit for a progressive disease like cystinosis.

The work of Cherqui and her colleagues may have wider applications for other genetic diseases, providing proof of principle that adult stem cell transplants may be successful in humans for genetic diseases with systemic defects, especially those of a progressive nature.

Cherqui expects to spend the next several years analyzing the safety of genetically modified autologous (obtained from the same individual) bone marrow transplants in the cystinosis mouse and other models before moving on to human clinical trials.

In addition to Cherqui, authors of the study "Successful treatment of the murine model of cystinosis using bone marrow cell transplantation" include first author Kimberly Syres of Scripps Research; Frank Harrison, Matthew Tadlock, and Daniel R. Salomon of Scripps Research; James V. Jester and Jennifer Simpson of the University of California, Irvine; and Subhojit Roy of the University of California, San Diego.

This work was funded by the Cystinosis Research Foundation.


Story Source:

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


Cite This Page:

Scripps Research Institute. "Rare Genetic Disease Successfully Reversed Using Stem Cell Transplantation." ScienceDaily. ScienceDaily, 18 September 2009. <www.sciencedaily.com/releases/2009/09/090917131656.htm>.
Scripps Research Institute. (2009, September 18). Rare Genetic Disease Successfully Reversed Using Stem Cell Transplantation. ScienceDaily. Retrieved November 21, 2014 from www.sciencedaily.com/releases/2009/09/090917131656.htm
Scripps Research Institute. "Rare Genetic Disease Successfully Reversed Using Stem Cell Transplantation." ScienceDaily. www.sciencedaily.com/releases/2009/09/090917131656.htm (accessed November 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

UN Says It Will Scale Up Its Ebola Response

UN Says It Will Scale Up Its Ebola Response

AFP (Nov. 20, 2014) UN Resident Coordinator David McLachlan-Karr and WHO representative in the country Daniel Kertesz updated the media on the UN Ebola response on Wednesday. Duration: 00:51 Video provided by AFP
Powered by NewsLook.com
Takata Offers "sincerest Condolences" To Victims of Malfunctioning Airbag

Takata Offers "sincerest Condolences" To Victims of Malfunctioning Airbag

Reuters - US Online Video (Nov. 20, 2014) U.S. Congress hears from a victim and company officials as it holds a hearing on the safety of Takata airbags after reports of injuries. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Obesity Costs Almost As Much As War And Terrorism

Obesity Costs Almost As Much As War And Terrorism

Newsy (Nov. 20, 2014) The newest estimate of the cost of obesity is pretty jarring — $2 trillion. But how did researchers get to that number? Video provided by Newsy
Powered by NewsLook.com
Calling All Men: Here's Your Chance to Experience Labor Pains

Calling All Men: Here's Your Chance to Experience Labor Pains

Reuters - Light News Video Online (Nov. 20, 2014) Chinese hospital offers men a chance to experience the pain of child birth via electric shocks. Sharon Reich reports. Video provided by Reuters
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