Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Patient-Specific Stem Cells and Personalized Gene Therapy

Published: Saturday, July 12, 2014
Last Updated: Saturday, July 12, 2014
Bookmark and Share
Patients’ own cells transformed into model for studying disease and developing potential treatment.

Columbia University Medical Center (CUMC) researchers have created a way to develop personalized gene therapies for patients with retinitis pigmentosa (RP), a leading cause of vision loss.

The approach, the first of its kind, takes advantage of induced pluripotent stem (iPS) cell technology to transform skin cells into retinal cells, which are then used as a patient-specific model for disease study and preclinical testing.

Using this approach, researchers led by Stephen H. Tsang, MD, PhD, showed that a form of RP caused by mutations to the gene MFRP (membrane frizzled-related protein) disrupts the protein that gives retinal cells their structural integrity. They also showed that the effects of these mutations can be reversed with gene therapy. The approach could potentially be used to create personalized therapies for other forms of RP, as well as other genetic diseases. The paper was published recently in the online edition of Molecular Therapy, the official journal of the American Society for Gene & Cell Therapy.

“The use of patient-specific cell lines for testing the efficacy of gene therapy to precisely correct a patient’s genetic deficiency provides yet another tool for advancing the field of personalized medicine,” said Dr. Tsang, the Laszlo Z. Bito Associate Professor of Ophthalmology and associate professor of pathology and cell biology.

While RP can begin during infancy, the first symptoms typically emerge in early adulthood, starting with night blindness. As the disease progresses, affected individuals lose peripheral vision. In later stages, RP destroys photoreceptors in the macula, which is responsible for fine central vision. RP is estimated to affect at least 75,000 people in the United States and 1.5 million worldwide.

More than 60 different genes have been linked to RP, making it difficult to develop models to study the disease. Animal models, though useful, have significant limitations because of interspecies differences. Researchers also use human retinal cells from eye banks to study RP. As these cells reflect the end stage of the disease process, however, they reveal little about how the disease develops. There are no human tissue culture models of RP, as it would dangerous to harvest retinal cells from patients. Finally, human embryonic stem cells could be useful in RP research, but they are fraught with ethical, legal, and technical issues.

The use of iPS technology offers a way around these limitations and concerns. Researchers can induce the patient’s own skin cells to revert to a more basic, embryonic stem cell–like state. Such cells are “pluripotent,” meaning that they can be transformed into specialized cells of various types.

In the current study, the CUMC team used iPS technology to transform skin cells taken from two RP patients-each with a different MFRP mutation-into retinal cells, creating patient-specific models for studying the disease and testing potential therapies.

By analyzing these cells, the researchers found that the primary effect of MFRP mutations is to disrupt the regulation of actin, the protein that makes up the cytoskeleton, the scaffolding that gives the cell its structural integrity. “Normally, the cytoskeleton looks like a series of connected hexagons,” said Dr. Tsang. “If a cell loses this structure, it loses its ability to function.”

The researchers also found that MFRP works in tandem with another gene, CTRP5, and that a balance between the two genes is required for normal actin regulation.

In the next phase of the study, the CUMC team used adeno-associated viruses (AAVs) to introduce normal copies of MFRP into the iPS-derived retinal cells, successfully restoring the cells’ function. The researchers also used gene therapy to “rescue” mice with RP due to MFRP mutations. According to Dr. Tsang, the mice showed long-term improvement in visual function and restoration of photoreceptor numbers.

“This study provides both in vitro and in vivo evidence that vision loss caused by MFRP mutations could potentially be treated through AAV gene therapy,” said coauthor Dieter Egli, PhD, an assistant professor of developmental cell biology (in pediatrics) at CUMC, who is also affiliated with the New York Stem Cell Foundation.

Dr. Tsang thinks this approach could also be used to study other forms of RP. “Through genome-sequencing studies, hundreds of novel genetic spelling mistakes have been associated with RP,” he said. “But until now, we’ve had very few ways to find out whether these actually cause the disease. In principle, iPS cells can help us determine whether these genes do, in fact, cause RP, understand their function, and, ultimately, develop personalized treatments.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,300+ scientific posters on ePosters
  • More Than 4,900+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Can We Break the Link Between Obesity and Diabetes?
Columbia University researchers identify a key molecule involved in the development of type 2 diabetes.
Tuesday, May 31, 2016
GI Problems in Autism May Originate in Genes
Gene linked to autism lowers serotonin activity in mice, slows movement in gut.
Tuesday, April 26, 2016
Virus Causing Tilapia Die-Offs Identified
Discovery of the virus causing Tilapia die-offs in Israel and Ecuador points the way to protecting a fish that feeds multitudes.
Wednesday, April 06, 2016
Celiac Disease Risk Linked to Non-coding RNA
Suggests factors outside of protein-coding genes play a role in celiac disease.
Friday, April 01, 2016
New Haploid Embryonic Stem Cell Line
The haploid stem cells may yield new genetic screening tools and therapies.
Thursday, March 17, 2016
Core Symptom of Schizophrenia Eliminated
Team uses chemical compound to restore affected brain regions; findings could lead to new treatment strategies.
Friday, February 19, 2016
New Way to Identify Brain Tumor Aggressiveness
Looking at a brain tumor’s epigenetic signature may help guide therapy.
Friday, January 29, 2016
Useful Colon Cancer Biomarker Discovered
Biomarker is detectable with simple, inexpensive test.
Monday, January 25, 2016
Link Between Congenital Heart, Brain Disorders
Tools of precision medicine may lead to earlier identification and treatment of children with neurodevelopmental disorders.
Thursday, December 10, 2015
Engineers Build Biologically Powered Chip
System combines biological ion channels with solid-state transistors to create a new kind of electronics.
Wednesday, December 09, 2015
World’s First Therapeutic Venom Database
Open-source library describes nearly 43,000 effects on the human body.
Thursday, November 26, 2015
What Do Animal Viruses Have to Do with Human Health?
Simon Anthony studies animal infections to prevent outbreaks in people.
Monday, September 28, 2015
Dentists Tapped for New Role: Drug Screenings
A visit to the dentist has the potential to be more than a checkup of our teeth as patients are increasingly screened for medical conditions like heart disease and diabetes.
Tuesday, August 18, 2015
Computer Model Forecasts Flu Outbreaks in Subtropical Climate
Study in Hong Kong predicts outbreaks by flu strains and is first to forecast flu in a subtropical climate.
Friday, August 07, 2015
Long-term Memories Are Maintained by Prion-like Proteins
Research from Eric Kandel’s lab at Columbia University Medical Center has uncovered evidence of a system in the brain that persistently maintains memories for long periods of time.
Friday, July 03, 2015
Scientific News
Breakthrough Flu Vaccine Inhibited by Pre-existing Antibodies
Universal truths – how existing antibodies are sabotaging the most promising new human flu vaccines.
Researchers Develop Software That Could Facilitate Drug Development
AptaTRACE can identify aptamers, potentially speed drug advancement.
Gene Therapy for Metabolic Liver Diseases
Researchers have tested gene therapy in pigs from hereditary tyrosinemia type 1, with corrected liver cells being transplanted into the diseased liver.
Zika Vaccine Candidates Show Promise
Two experimental vaccines have shown promise against a major viral strain responsible for the Brazilian Zika outbreak.
New Medication Shows Promise Against Liver Fibrosis in Animal Studies
Liver fibrosis is a gradual scarring of the liver that puts people at risk for progressive liver disease and liver failure.
Raw Eggs Deemed Safe to Eat
A report published today by the Advisory Committee on the Microbiological Safety of Food (ACMSF) into egg safety has shown a major reduction in the risk from salmonella in UK eggs.
Monitoring TTX Toxin in Shellfish
In a number of small studies, mussels and oysters from the eastern and northern part of the Oosterschelde in Holland were found to contain tetrodotoxin (TTX).
Gene Terapy for Muscle Wasting Developed
New gene therapy could save millions of people suffering from muscle wasting disease.
NIH Begins Yellow Fever Vaccine Trial
NIH has initiated an early-stage clinical trial of a vaccine to protect against yellow fever.
Gene-Editing 'Toolbox' Targets Multiple Genes Simultaneously
Researchers have designed a system that modifies, or edits, multiple genes in a genome at once while minimising unintentional effects.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!