Blind boy, 14, has his vision restored by eyedrops that use inactivated HERPES VIRUS in potential breakthrough that could help millions

A 14-year-old who was blind for most of his life can now see after an enterprising Miami doctor reformulated the world’s first topical gene therapy as eye drops.

The drug was recently approved as a topical gel to be rubbed on skin lesions caused by a sporadic disease that leaves severe wounds and scar tissue, sometimes resulting in fingers and toes fusing together.

The disease, which can also cause scar tissue on the eyeballs, is part of a larger group of rare conditions called epidermolysis bullosa (EB), which affects about one in 50,000 children.

The patient is Antonio Vento Carvajal, born with dystrophic epidermolysis bullosa, which causes defects in the gene responsible for the production of collagen 7, a protein that holds the layers of the skin together. Scars on his corneas had built up over time, deteriorating his eyesight to the point that he didn’t feel safe walking around.

Mr. Carvajal successfully participated in a clinical trial testing the topical gel on EB-related skin lesions. His doctor Alfonso Sabater, encouraged by Antonio’s progress, suggested that the gel that used a deactivated herpes virus to deliver working copies of a collagen-producing gene could be reconfigured as eye drops – and he was right.

Mr Carvajal’s doctor, Alfonso Sabater, saw how successful a topical gene therapy was for his patient’s condition and approached the drug manufacturer to create a version that could be applied to the eyes

The patient’s eyes recovered from the last operation, and with the help of the drops, his sight has been restored almost perfectly.

Dystrophic epidermolysis bullosa (DEB) is one of the major forms of epidermolysis bullosa that impairs the production of collagen encoded in the COL7A1 gene. About 3,000 people in the world have it.

Collagen forms the skin’s anchoring fibrils, or special structures in the skin and other tissues that act like strong glue to hold the outermost layer of the skin — the epidermis — together with the layer below it called the dermis.

Without a fully functioning COL7A1 gene, the connection between both layers of skin weakens, making them extremely fragile to the point where the slightest friction can lead to blisters and open wounds that are susceptible to infection.

Those same anchoring fibrils in the skin are also located in the cornea, the transparent part of the eyeball. People with DEB who have a defective collagen-producing gene also lack that crucial connective tissue between the layers of the cornea, making painful abrasions and a buildup of scar tissue more likely.

Mr Carvajal, who arrived from Cuba with his family in 2012 on a special visa to undergo treatment for the rare condition, took part in a clinical trial for the therapy known as Vyjuvek, which uses an inactivated version of a herpes simplex virus to deliver working copies of that gene to the patient’s body.

They used an inactive herpes simplex virus type 1 (HSV-1) as the viral vector – a genetically modified virus used to deliver therapeutic genes to the patient’s cells – because it has more space on its genome compared to other vectors to carry large DNA sequences.

HSV is also very efficient at entering cells and delivering its genetic material.

Surgeries that attempted to remove the buildup of scar tissue on the teen’s eyes and at least partially restore his vision had proved unsuccessful, with the tissue growing back each time.

But Mr. Carvajal’s physician, Alfonso Sabater of the University of Miami Health System’s Bascom Palmer Eye Institute, was impressed with the therapy’s ability to heal his patient’s skin and approached the drug’s manufacturer, Krystal Biotech, to reconfigure it so that it can be administered safely into the patient’s eyes.

Dr. Sabater told Ophthalmology Times in May, “We presented this case and they were very interested in our patient and helped us develop the formulation for ocular treatment. So we approached the FDA and within a few months we were able to get approval for compassionate use of this drug on our patient.”

For his part, Suma Krishnan, president of R&D at Krystal said, “It didn’t hurt to try.”

After being blind for most of his 14 years, Antonio can now play video games with his friends and feel safer walking around

Dr. Sabater’s dogged efforts to find a cure for his patient’s eyes culminated in the drops that have proved so successful in recent times.

Mr Carvajal underwent surgery on his right eye last summer, after which Dr Sabater began treating him with the drops, which use the same liquid as the skin version, but without the added gel. The scar tissue has not grown back. Today, his vision in his right eye is near perfect at 20/25.

Dr. Sabater recently started treating Mr. Carvajal’s left eye, which had even more scar tissue than the right eye. The health of that eye is steadily improving, with vision close to 20/50.

The patient goes to Dr. Sabater for his monthly eye drops, all the while wearing long sleeves and pants to cover his vulnerable skin from abuse. The slightest touch can injure him.

He still uses the topical gel for his skin sores, which was approved by the Food and Drug Administration in May.

Having been blind for much of his young life, Antonio can now enjoy typical teenage pastimes such as playing videos with his friends. He also walks around the world more confidently than before.

But just because people technically have access to the medication to treat their EB doesn’t mean they necessarily will be able to. Like most gene therapies, Vyjuvek is prohibitively expensive if you’re not lucky enough to participate in a clinical trial with an annual cost of about $631,000 per patient. Insurance may not cover all or even part of those costs.

Price tag aside, developing a gene therapy that addresses the root cause of a disease rather than just addressing the symptoms by delivering a functional copy of the faulty gene or modifying the patient’s own genes is exciting, doctors say.

And because gene therapies can be tailored to a particular patient’s physiology, the overall chances of success are higher, while those of serious side effects are significantly lower.