Navigation Links
Gene therapy safety trial for childhood blindness under way
Date:11/19/2007

GAINESVILLE, Fla. Three decades have passed since gene therapy pioneer William W. Hauswirth, Ph.D., and his colleagues at the University of Florida began work on a virus that could safely deliver corrective genes into living animals.

Its been six years since a multi-university team used gene therapy to give sight to puppies born with a defect that causes blindness.

Now the gene-transfer technique is being tested for safety in people in a phase 1 clinical research study conducted by the University of Pennsylvania and the University of Florida with support from the National Eye Institute of the National Institutes of Health.

A young adult with a form of hereditary blindness called Leber congenital amaurosis type 2, or LCA2, received an injection of trillions of replacement genes into the retina of one eye this month, making the volunteer one of the first people in the world to undergo the procedure. Shalesh Kaushal, M.D., Ph.D., an assistant professor of ophthalmology at UF, performed the gene transfer.

The volunteer was discharged last week from the General Clinical Research Center at UF.

In all, six adults and then three children between the ages of 8 and 17 will undergo the gene-transfer procedure at UF over the next year or more before safety data are fully evaluated. Names are not being disclosed for privacy reasons. Potential risks are discussed with prospective participants as part of an extensive screening and informed consent process.

This is the first study of its kind to investigate inherited blindness, said Barry J. Byrne, M.D., Ph.D., a professor of molecular genetics and microbiology and director of UFs Powell Gene Therapy Center. The accomplishment reflects a great deal of work and dedication on the part of Dr. Hauswirth, as well as many other scientists and physicians, including Samuel G. Jacobson, M.D. Ph.D., professor of ophthalmology of the University of Pennsylvania, and literally dozens of people who were involved in manufacturing and safety testing the gene transfer agent here at UF.

Hauswirth and Jacobson the trials principal investigator were among a multicenter team of NEI-supported clinicians and scientists that first established proof-of-concept for gene transfer for LCA in rodent models of the disease and in a breed of vision-impaired dogs called Briards. Restoration of visual function in dogs occurred in 2001 and has been described as remarkable and long-lasting.

Six years have gone by since the Briard puppies Lancelot was the breakout star, going on to shake paws with lawmakers on Capitol Hill acquired sight.

The idea of the therapy is simple, said Hauswirth, UFs Rybaczki-Bullard professor of ophthalmic molecular genetics. If cells are missing a gene for a vital function, such as vision, the therapy is to replace that gene.

After rigorous preclinical safety studies in animals, including demonstrating the safety of the procedure in non-human primates, the investigators began a human clinical trial.

The effort involved intense collaboration with several investigators playing major roles, according to Jacobson. A short list of the key clinicians and scientists from Penn includes Artur V. Cideciyan, Ph.D., a research associate professor, and Tomas S. Aleman, M.D., a research assistant professor, both from the department of ophthalmology.

In LCA-type diseases, photoreceptor cells are unable to respond to light. NEI and NEI-supported researchers have found that LCA2 is caused by mutations in the RPE65 gene, which produces a protein with the same name that is vital for vision. This trial will evaluate the use of a modified adeno-associated virus an apparently harmless virus that already exists in most people to deliver RPE65 to the retina.

Viruses have evolved a way to get into cells very efficiently, more efficiently than anything else we know to deliver a piece of genetic material to a cell, Hauswirth said. So all were doing is using evolution to our advantage in this case, to deliver our therapeutic gene.

Instrumental in developing the first gene-carrying adeno-associated vectors were eminent scholar Nicholas Muzyczka, Ph.D., a professor of molecular genetics and microbiology at UF, and Kenneth Berns, M.D., Ph.D., director of the UF Genetics Institute. In 1992 Muzyczka and Berns patented a form of the adeno-associated virus capable of introducing foreign DNA into mammalian cells. Terence Flotte, M.D., former chairman of UFs department of pediatrics and the current dean of the School of Medicine at the University of Massachusetts Medical School, was instrumental in the early organization of the trial. Byrne is the principal investigator at UF.

The actual medical technique used to transfer the gene is not unusual, said Kaushal, who directs the vitreoretinal service in the UF College of Medicine.

The procedure involves two incisions that give the surgeon access to the surface of the retina, Kaushal said. Then, fluid containing the virus is injected with a syringe and it creates a bubble. The virus will then be taken up by the photoreceptor cells and the retinal pigment epithelial cells and will theoretically produce the protein that these patients are missing.

LCA2 affects about 2,000 people in the United States and is one of several incurable forms of blindness collectively known as retinitis pigmentosa, which in turn affects about 200,000 Americans.

Children with LCA2 experience major visual disability that can lead to total vision loss in adulthood. Although vision loss is severe, the structure of the retina including its connection to the brain can remain relatively intact for decades before the photoreceptor cells degenerate.


'/>"/>

Contact: John Pastor
jdpastor@ufl.edu
352-273-5815
University of Florida
Source:Eurekalert

Related medicine news :

1. Vision restoration therapy shown to improve brain activity in brain injured patients
2. HIV therapy in pregnancy-data support WHO recommendations
3. Family-based treatment more effective than supportive psychotherapy in treating bulimia
4. Trial to Test Gene Therapy for Angina in Women
5. One of the Largest Post-WHI Physician Surveys Shows More Education is Needed: Patient Misinformation About Hormone Therapy Remains High
6. Aromatherapy Gift Line Sheds Humorous Light on Modern Therapy
7. Chemotherapy may be culprit for fatigue in breast cancer survivors
8. Atlanta Falcons Physical Therapy Centers Set to Launch This Fall
9. New Drug No Substitute for Standard Blood-Clot Therapy
10. Stem Cell Therapy Disappoints Against Rare Kidney Ailment
11. Nucletron Announces Management Buy-Out to More Effectively Meet the Demands of Its Customers and the Radiation Therapy Community
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... ... First Choice Emergency Room , the largest network of independent freestanding ... of its new Mesquite-Samuell Farm facility. , “We are pleased to announce Dr. ... James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. , Dr. ...
(Date:6/25/2016)... ... June 25, 2016 , ... Dr. Calvin Johnson ... Recently, he has implemented orthobiologic procedures as a method for treating his patients. ... the first doctors to perform the treatment. Orthobiologics are substances that orthopaedic surgeons ...
(Date:6/25/2016)... Canada (PRWEB) , ... June 25, 2016 , ... Conventional ... pursuit of success. In terms of the latter, setting the bar too high can ... risk more than just slow progress toward their goal. , Research from ...
(Date:6/24/2016)... , ... June 24, 2016 , ... Those who have ... these feelings, many turn to unhealthy avenues, such as drug or alcohol abuse, as ... Michigan, has released tools for healthy coping following a traumatic event. , Trauma sufferers ...
(Date:6/24/2016)... ... 24, 2016 , ... Marcy was in a crisis. Her son James, eight, was out of ... verbally and physically. , “When something upset him, he couldn’t control his emotions,” remembers Marcy. ... throw rocks at my other children and say he was going to kill them. ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... Research and Markets has announced the ... to 2022" report to their offering. ... patients with kidney failure, it replaces the function of kidneys ... blood and thus the treatment helps to keep the patient ... Increasing number of ESRD patients & substantial ...
(Date:6/23/2016)... June 23, 2016  In a startling report released today, ... residents by lacking a comprehensive, proven plan to eliminate prescription opioid ... ranking of how states are tackling the worst drug crisis in ... states – Kentucky , New Mexico ... . Of the 28 failing states, three – ...
(Date:6/23/2016)... Capricor Therapeutics, Inc. ... company focused on the discovery, development and commercialization ... in its ongoing randomized HOPE-Duchenne clinical trial (Halt ... its 24-patient target. Capricor expects the trial to ... 2016, and to report top line data from ...
Breaking Medicine Technology: