New Breakthroughs IN GENE THERAPY


Creed Pettit, Mathew Pray and Julio Adorno Nieves are among a select group of Bascom Palmer Eye Institute patients benefiting from a remarkable advance in treating incurable blinding conditions.

After receiving leading-edge gene therapy for inherited eye disorders, each patient’s vision improved dramatically.

“I could see a rainbow for the first time,” said Creed, a 9-year-old from Mount Dora, Florida, who was legally blind from Lebercongenital amaurosis (LCA) before receiving treatment last spring. “I can read now without a super-bright light and even read things written in pencil.”

LCA is an inherited retinal disease that causes severe visual impairment in infancy or early childhood. For more than a decade, Bascom Palmer’s clinicians and scientists have been in the forefront of gene therapy, contributing to research studies and leading clinical trials to stabilize or restore vision in adult and pediatric patients.

Today, the Institute has one of the largest gene therapy programs in the nation with additional clinical trials and studies coming soon.

“Gene therapy is a viable option to restore sight for people with inherited eye diseases,” said Byron Lam, M.D., professor of ophthalmology and holder of the Robert Z. and Nancy J. Greene Chair in Ophthalmology. “It is important that patients are seen by a clinician who can diagnose inherited eye disorders.

Genetic testing and careful evaluation are necessary to determine if these new therapies are appropriate for them. ”


Scientific researchers have identified more than 250 genes that play a role in inherited retinal diseases. Drawing on that knowledge, biomedical companies have focused on developing clinical treatments for a handful of those genes linked to rare blinding conditions, including achromatopsia, choroideremia, Lebercongenital amaurosis, Leber hereditary optic neuropathy, X-linked retinoschisis, Stargardt macular dystrophy and X-linked retinitispigmentosa.

In gene therapy, a tiny dose of adeno-associated virus (AAV) is used as a transmission vector to carry functional new genes into the retina. Once delivered, the new genes use the body’s own cellular mechanisms to produce functional proteins with a therapeutic impact on the retinal cells.

Every step of the process has to be carefully managed for patient safety and maximum efficacy of the treatment, according to John Guy, M.D., professor of ophthalmology and the Rodgers Research Chair in Ophthalmology.

“We work as a team in these complex cases,” he said.

The multidisciplinary support for gene therapy includes the research pharmacy of the Sylvester Comprehensive Cancer Center of the University of Miami Miller School of Medicine, which stores the therapeutic vectors at -80 degrees Fahrenheit and delivers them to the operating room just in time for the procedures.

“We spend a lot of time planning cases, beginning with a comprehensive study of the patient’s retinas,” said Janet L. Davis, M.D., professor of ophthalmology and holder of the Leach Chair in Ophthalmology.

Advanced imaging technology, including optical coherence tomography (OCT) and fund us auto fluorescence is used to determine if a patient is a suitable candidate. Next, the surgical team carefully maps the patient’s retina to determine precisely whereto apply the gene-changing vector. For patient safety, only one eye is treated at a time.

“We have only one opportunity to get it right, because there may be an inflammatory reaction afterwards,” said Davis, adding that it takes courage for patients to participate in these clinical trials. “We are inspired by our patients, who often come from long distances for treatment, and strive to provide them with support throughout the process.”

During the gene therapy procedure for inherited retinal diseases, a space under the retina in the peripheral region of the macula (the central vision area of the retina) is created.

The fluid with the gene therapy vector is injected and spread to the targeted area of the retina while watching the macula with an imaging device to avoid potential complications. Initially, Lam and Davis took part in a Johnson & Johnson sponsored study using human umbilical stem cells to treat Stargardt macular dystrophy, a rare genetic disease.

“We were trained in the special surgical procedures for administering sub retinal injections,” said Davis. “Since then, we have continued to refine our techniques to benefit our patients.”

“Subsequently, a philanthropic donation to Bascom Palmer funded our first gene therapy trial,” said Lam. “That was for a phase II trial for choroideremia, and it opened the door for further studies.”

Since 2007, Davis and Gregori have performed approximately 40 gene therapy injections under the macula in patient eyes. Furthermore, the Institute’s physicians have contributed to multiple research studies involving gene therapy.

For instance, Guy has been involved in several clinical trials to treat Leber hereditary optic neuropathy (LHON), which is typically caused by a mutation area of the retina while watching the macula with an imaging device to avoid potential complications.

Ninel Gregori, M.D., associate professor of clinical ophthalmology, typically works with Davison gene therapy surgeries on adult patients, while Audrina M. Berrocal, M.D., a pediatric retinal surgeon and professor of clinical ophthalmology, usually operates on children.”

In 2016, during the first gene therapy trial at Bascom Palmer, we integrated OCT imaging into the surgery so the surgeons could watch the injection in real time and ensure the medication was going to the proper place while avoiding complications,” said Gregori.

“We published this new technique for injecting the gene therapy in order to share our method with other surgeons.”

In the past decade, Bascom Palmer has built an extensive gene therapy program that includes ophthalmologists, genetic counselors and research scientists studying various forms of inherited eye diseases. Bascom Palmer is changing the future of ophthalmology and changing lives.

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