Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Two Treatments for Retinitis Pigmentosa Move Closer to Clinical Trials

Published: Friday, December 21, 2012
Last Updated: Friday, December 21, 2012
Bookmark and Share
One treatment involves skin-derived induced pluripotent stem (iPS) cell grafts, the other gene therapy.

The treatments have been shown to produce long-term improvement in visual function in mouse models of retinitis pigmentosa (RP), according to the Columbia University Medical Center (CUMC) scientists who led the studies. At present, there is no cure for RP, the most common form of inherited blindness.

“While these therapies still need to be refined, the results are highly encouraging,” said Stephen H. Tsang, MD, PhD, associate professor of pathology & cell biology and of ophthalmology at Columbia University Medical Center and an ophthalmologist at NewYork-Presbyterian Hospital/CUMC, the leader of both studies. “We’ve never seen this type of improvement in retinal function in mouse models of RP. We hope we may finally have something to offer patients with this form of vision loss.”

The stem cell study was published in the journal Molecular Medicine. The gene therapy study was published in Human Molecular Genetics.

RP encompasses a group of inherited eye diseases that cause progressive loss of photoreceptor cells, specialized neurons found in the retina. While RP can appear during infancy, the first symptoms typically appear in early adulthood, beginning 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. Mutations in at least 50 genes have been found to cause the disease, which affects about 1.5 million people worldwide.

In the Molecular Medicine study, the CUMC researchers tested the long-term safety and efficacy of using iPS cell grafts to restore visual function in a mouse model of RP. Like embryonic stem cells, iPS cells are “pluripotent” — that is, they are capable of developing into any cell type. However, iPS cells are not derived from embryos but from adult cells, in this case from human skin cells. The cells were administered, via injection directly underneath the retina, when the mice were five days old.

The iPS cells assimilated into the host retina without disruption, and none of the mice receiving transplants developed tumors over their lifetimes, the researchers reported. The iPS cells were found to express markers specific to retinal pigmented epithelium (the cell layer adjacent to the photoreceptor layer), showing that they had the potential to develop into functional retinal cells. Using electroretinography, a standard method for measuring retinal function, the researchers found that the visual function of the mice improved after treatment and the effect was long lasting. “This is the first evidence of lifelong neuronal recovery in an animal model using stem cell transplants, with vision improvement persisting throughout the lifespan,” said Dr. Tsang.

In 2011, the FDA approved clinical trials of embryonic stem cell transplants for the treatment of macular degenerations, but such therapy requires immunosuppression. “Our study focused on patient-specific iPS cells, which offer a compelling alternative,” said Dr. Tsang. “The iPS cells can provide a potentially unlimited supply of cells for functional rescue and optimization. Also, since they would come from the patient’s own body, immunosuppression would not be necessary to prevent rejection after transplantation.”

In theory, iPS cell transplants could also be used to treat age-related macular degeneration, the leading cause of vision loss among older adults, said Dr. Tsang.

In the Human Molecular Genetics study, the CUMC researchers tested whether gene therapy could be used to improve photoreceptor survival and neuronal function in mice with RP caused by a mutation to a gene called phosphodiesterase-alpha (Pde6α) — a common form of the disease in humans. To treat the mice, the researchers used adeno-associated viruses (AAV) to ferry correct copies of the gene into the retina. The AAV were administered by a single injection in one eye, with the other eye serving as a control.

When the mice were examined at six months of age (over one-third of the mouse lifespan), photoreceptor cells were found in the treated eyes but not in the untreated eyes, the researchers reported. More important, the treated eyes showed functional visual responses, while the untreated eyes had lost all vision.

“These results provide support that RP due to PDE6α deficiency in humans is also likely to be treatable by gene therapy,” said Dr. Tsang.

CUMC and its teaching-hospital affiliate, NewYork-Presbyterian Hospital, are part of an international consortium that was recently formed to bring this PDE6A gene therapy to patients. Pending FDA approval, Phase I/II clinical trials could begin within a year.

The Molecular Medicine paper is titled, “Stem Cell (iPS) Grafts in a Preclinical Model of Retinitis Pigmentosa.” The other contributors are Yao Li (CUMC), Yi-Ting Tsai (CUMC), Chun-Wei Hsu (CUMC), Deniz Erol (CUMC), Jin Yang (CUMC), Wen-Hsuan Wu (CUMC), Richard J Davis (CUMC), and Dieter Egli (New York Stem Cell Foundation Laboratory). This study was supported by the NYSTEM co26448, National Institutes of Health (grants 5P30CA013696 and P30EY019007), Research to Prevent Blindness, the Joan and Michael Schneeweiss Stem Cell Fund, and the Foundation Fighting Blindness.

The Human Molecular Genetics paper is titled, “Gene therapy provides long-term visual function in a pre-clinical model of retinitis pigmentosa.” The other contributors are Katherine J. Wert (CUMC), Richard J. Davis (CUMC), Javier Sancho-Pelluz (CUMC), and Patsy M. Nishina (Jackson Laboratory, Bar Harbor, Maine). The research was supported by the National Institute of Health (grants 5P30EY019007 and R01EY018213), the National Cancer Institute (grant 5P30CA013696), Research to Prevent Blindness, the Department of Defense (grant TS080017-W81XWH-09-1-0575), the Foundation Fighting Blindness, the Joan and Michael Schneeweiss Stem Cell Fund, the Barbara and Donald Jonas Family Fund, and the Tistou and Charlotte Kerstan Foundation.


Further Information
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 2,500+ scientific posters on ePosters
  • More than 3,700+ 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

Patient-Specific Stem Cells and Personalized Gene Therapy
Patients’ own cells transformed into model for studying disease and developing potential treatment.
Saturday, July 12, 2014
Researchers use Adult Stem Cells to Create Soft Tissue
Columbia researchers receive $2.5M NIH grant to support stem cell research to develop tissue for facial reconstruction.
Monday, July 02, 2007
Definition of Embryo Death Criteria may Open Doors for Stem Cell Research
By confirmation of embryo death, embryos could be harvested, just as organs are for transplantation, in order to generate stem cells for research and, ultimately, therapeutic purposes.
Tuesday, June 06, 2006
Scientific News
The Mending Tissue - Cellular Instructions for Tissue Repair
NUS-led collaborative study identifies universal mechanism that explains how tissue shape regulates physiological processes such as wound healing and embryo development.
Tissue Bank Pays Dividends for Brain Cancer Research
Checking what’s in the bank – the Brisbane Breast Bank, that is – has paid dividends for UQ cancer researchers.
iPS Cells Discover Drug Target for Muscle Disease
Researchers have designed a model that reprograms fibroblasts to the early stages of their differentiation into intact muscle cells in a step towards a therapeutic for Duchenne muscular dystrophy.
Engineered Hot Fat Implants Reduce Weight Gain
Scientists at UC Berkeley have developed a novel way to engineer the growth and expansion of energy-burning “good” fat, and then found that this fat helped reduce weight gain and lower blood glucose levels in mice.
Transplanted Stem Cells Can Benefit Retinal Disease Sufferers
Tests on animal models show that MSCs secrete growth factors that suppress causes of diabetic retinopathy and macular degeneration.
MRI Scanners Can Steer Therapeutics to Specific Target Sites
Scientists from the University of Sheffield have discovered MRI scanners, normally used to produce images, can steer cell-based, tumour busting therapies to specific target sites in the body.
Team Finds Early Inflammatory Response Paralyzes T Cells
Findings could have enormous implications for immunotherapy, autoimmune disorders, transplants and other aspects of immunity.
Early Detection of Lung Cancer
The University of Manchester has signed a collaboration agreement with Abcodia to perform proteomics studies on a cohort of non-small cell lung cancer cases from the UKCTOCS biobank, with the aim of discovering new blood-based biomarkers for earlier detection of the disease.
Researchers Identify Drug Candidate for Skin, Hair Regeneration
Formerly undiscovered role of protein may lead to the development of new medications that stimulate hair and skin regeneration in trauma or burn victims.
Basis for New Treatment Options for a Fatal Leukemia in Children Revealed
Detailed molecular analyses allow new insights into the function of tumour cells and options for new treatments.
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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!