A 14-year-old boy who spent most of his life blind can now see after an enterprising Miami doctor reformulated the world’s first topical gene therapy into eye drops.
The drug was recently approved as a topical gel to rub on skin lesions caused by a sporadic disease that leaves severe wounds and scar tissue, sometimes resulting in fused fingers and toes.
The disease, which can also cause scar tissue buildup on the eyeballs, belongs to a larger group of rare disorders called epidermolysis bullosa (EB) that affects one in 50,000 children.
The patient is Antonio Vento Carvajal, who was born with dystrophic epidermolysis bullosa that causes faults in the gene responsible for producing collagen 7, a protein that holds the layers of skin together. The scars on his corneas had accumulated over time, causing his vision to deteriorate so much that he didn’t feel safe walking.
Mr. Carvajal was a very successful participant in a clinical trial testing the topical gel for EB-related skin lesions. His doctor Alfonso Sabater, encouraged by Antonio’s progress, postulated 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.
Antonio Vento Carvajal came to the US with his family in 2012 from Cuba to seek special care for his genetic disorder. Several surgeries to remove scar tissue from his eyes were unsuccessful, as the tissue always grew back.
Carvajal’s doctor, Alfonso Sabater, saw the success of a topical gene therapy for his patient’s condition and approached the drug maker about making a version to apply to the eyes.
The patient’s eyes recovered from the latest round of surgery, and with the help of the drops, his vision was restored to near perfection.
Dystrophic epidermolysis bullosa (DEB) is one of the main forms of epidermolysis bullosa that impedes the production of collagen encoded in the COL7A1 gene. Approximately 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 a strong glue to hold the outer layer of skin, the epidermis, together with the layer below called the dermis.
Without a fully functioning COL7A1 gene, the connection between the two layers of skin becomes weaker, making them extremely fragile to the point where even the slightest friction can lead to blisters and open sores vulnerable to infection.
Those same skin-anchoring fibrils also reside in the cornea, the transparent part of the eyeball. People with DEB who have a faulty gene that makes collagen also lack that crucial connective tissue between the layers of the cornea, making painful abrasions and scar tissue buildup more likely.
Carvajal, who came with his family from Cuba in 2012 on a special visa to receive treatment for the rare disorder, has enrolled 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 a patient’s body.
They used an inactivated herpes simplex virus type 1 (HSV-1) as a viral vector, a genetically modified virus used to deliver therapeutic genes to patient cells, because it has more space in 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 in the teen’s eyes and restore his vision, at least partially, were unsuccessful, with the tissue growing back each time.
But Carvajal’s doctor, Alfonso Sabater, of the University of Miami Health System’s Bascom Palmer Eye Institute, impressed with the therapy’s ability to heal his patient’s skin, approached the drug’s maker, Krystal Biotech, to reconfigure it in such a way that it would be delivered safely into the patient’s eyes.
Dr Sabater told the Ophthalmology Times in May: ‘We presented this case and they were very interested in our patient and helped us develop the formulation for eye treatment. So we approached the FDA, and within a few months, we were able to get compassionate use approval for this drug in our patient.’
Suma Krishnan, president of R&D at Krystal, for his part, said: “It didn’t hurt to try it.”
Having spent most of his 14 years legally blind, Antonio is now able to play video games with his friends and feels safer walking around.
Dr. Sabater’s dogged attempts to find a treatment for his patient’s eyes culminated in the drops that have been so successful of late.
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, just 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 began treating Mr. Carvajal’s left eye, which had even more scar tissue than his right. The health of that eye is steadily improving, with the power of vision measuring close to 20/50.
The patient goes to see Dr. Sabater for his monthly eye drops, while wearing long sleeves and pants to cover his vulnerable skin from assault. The slightest contact could hurt him.
He still uses the topical gel for skin sores, which was approved by the Food and Drug Administration in May.
After spending much of his young life legally blind, Antonio is now able to enjoy typical teenage hobbies like playing videos with his friends. He is also more confident to walk the world than before.
But just because people can technically access the drug to treat their EB, doesn’t mean they will necessarily be able to. Like most gene therapies, Vyjuvek is cost-prohibitive if you’re not lucky enough to participate in a clinical trial costing about $631,000 per patient per year. Insurance may not cover all or even part of that cost.
Price aside, developing a gene therapy that addresses the root cause of a disease rather than just the symptoms by delivering a working copy of the faulty gene or modifying the patient’s own genes is exciting, according to the doctors.
And because gene therapies can be tailored to suit a particular patient’s physiology, the overall chances of success are higher, while the chances of serious adverse effects are markedly lower.