Navigation Links
Patient-specific stem cells and personalized gene therapy
Date:7/10/2014

NEW YORK, NY (July 10, 2014) 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 celllike 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 patientseach with a different MFRP mutationinto 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."


'/>"/>

Contact: Lucky Tran
lt2549@cumc.columbia.edu
212-305-3689
Columbia University Medical Center
Source:Eurekalert  

Related biology news :

1. Tortoise and the hare: New drug stops rushing cancer cells, slow and steady healthy cells unharmed
2. Stem cells can repair a damaged cornea
3. Scientists produce eye structures from human blood-derived stem cells
4. Study demonstrates cells can acquire new functions through transcriptional regulatory network
5. Epigenetic signatures direct the repair potential of reprogrammed cells
6. Researchers print live cells with a standard inkjet printer
7. Nanopills release drugs directly from the inside of cells
8. Protein jailbreak helps breast cancer cells live
9. Newly found protein helps cells build tissues
10. BU researchers derive purified lung and thyroid progenitors from embryonic stem cells
11. Housekeeping mechanism for brain stem cells discovered
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Patient-specific stem cells and personalized gene therapy
(Date:2/4/2016)... -- The field of Human Microbiome research and ... hubs of the biotechnology industry. While the Human ... human microbiota, have garnered a lot of attention ... has literally exploded in terms of both basic ... on biomedical aspects of research, development, and commercial ...
(Date:2/3/2016)... 3, 2016 ... the "Emotion Detection and Recognition Market ... Others), Software Tools (Facial Expression, Voice Recognition ... Regions - Global forecast to 2020" ... http://www.researchandmarkets.com/research/d8zjcd/emotion_detection ) has announced the addition ...
(Date:2/2/2016)... 2016 Technology Enhancements Accelerate Growth of X-ray Imaging ... digital and computed radiography markets in Thailand ... Indonesia (TIM). It provides an in-depth ... well as regional market drivers and restraints. The study ... and market attractiveness, both for digital and computed radiography. ...
Breaking Biology News(10 mins):
(Date:2/8/2016)... ... 2016 , ... Franz Inc. , an early innovator ... announced the availability of AllegroGraph 6, the leading Semantic Graph Database with certification ... Program (CCPT). AllegroGraph is the first Semantic Graph Database to be certified ...
(Date:2/8/2016)... England , February 8, 2016 ... Ltd ("Atlas Genetics" or the "Company"), the ultra-rapid Point-Of-Care (POC) ... to CE Mark its Chlamydia trachomatis (CT) test to be ... of the IVD Directive (98/79/EC), the CT test is now ... --> --> The launch of the io® ...
(Date:2/5/2016)... Feb. 5, 2016  In the pharmaceutical industry the ... host of launch activities including the identification and engagement ... activity is especially high in the oncology therapeutic area ... Practices and the Role of Medical Affairs in Oncology ... on oncology therapies find better ways to utilize medical ...
(Date:2/4/2016)... ... February 04, 2016 , ... Morf ... today announced an interactive FDA compliance training course, Writing Effective ... Professional Society) accredited interactive course on Morf Playbook—now conveniently available on smartphones and ...
Breaking Biology Technology: