Navigation Links
Rare genetic disease successfully reversed using stem cell transplantation
Date:9/17/2009

LA JOLLA, CA September 17, 2009 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.

"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 rareaffecting an estimated 500 people in the United States and 2,000 worldwideit 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.


'/>"/>

Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

Related biology news :

1. Does the desire to consume alcohol and tobacco come from our genetic makeup?
2. Diverse genetic abnormalities lead to NF-κB activation in multiple myeloma
3. Many parents at-risk for cancer disclose genetic test results to children
4. Genetics determine optimal drug dose of common anticoagulant
5. Claims of sex-related differences in genetic association studies often not properly validated
6. American College of Medical Genetics responds to new FDA labeling decision for warfarin
7. UNC study questions FDA genetic-screening guidelines for cancer drug
8. Genome study shines light on genetic link to height
9. Selexis Announces Advanced Approach to Maximize Power of Genetic Elements for Rapid Development of High Performance Cell Lines
10. Genes, Environment and Health Initiative invests in genetic studies, environmental monitoring
11. Rutgers Genetics receives $7.8 million for autism research
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/25/2016)... Jan. 25, 2016  Glencoe Software, the world-leading supplier ... publication industries, will provide the data management solution OMERO ... Photo ... Phenotypic analysis measures the characteristics ... allowing comparisons between states such as health and disease, ...
(Date:1/20/2016)... --  MedNet Solutions , an innovative SaaS-based eClinical technology ... is pleased to announce the attainment of record-setting corporate ... of the company,s laser focus on (and growing international ... comprehensive, easy-to-use and highly affordable cloud-based technology platform. ... growth achievements in 2015 include: , Record ...
(Date:1/13/2016)... 13, 2016 ... of the  "India Biometrics Authentication & ... (2015-2020)"  report to their offering.  ... announced the addition of the  "India ... Estimation & Forecast (2015-2020)"  report ...
Breaking Biology News(10 mins):
(Date:2/6/2016)... ... February 06, 2016 , ... Contact:, Abby Mitchell, Communications ... in Education Sponsors Teacher Training Program , Bite of Science Dinner Event to ... for Excellence in Education (CEE) will sponsor a Bite of Science professional enrichment ...
(Date:2/5/2016)... DIEGO , Feb. 5, 2016 On ... region,s trusted information source for community, health and disaster ... Diego) will integrate to enhance care coordination and ... to the services they need and to better connect ... improve care.   San Diego ...
(Date:2/4/2016)... ... February 04, 2016 , ... ... training, today announced an interactive FDA compliance training course, Writing ... Affairs Professional Society) accredited interactive course on Morf Playbook—now conveniently available on smartphones ...
(Date:2/4/2016)... ... , ... Shimadzu Scientific Instruments will showcase several new products, ... sessions, and present on the analysis of mycotoxins and medical cannabis at the ... at the Georgia World Congress Center in Atlanta, Georgia. , Attendees should ...
Breaking Biology Technology: