PENNSYLVANIA, May 4 — A gene therapy that helped restore sight in patients with a rare form of childhood blindness appears to wane with time, a sign the cutting-edge field may not be able to cure some ailments with a single course of treatment.
The findings from a University of Pennsylvania study were published yesterday in the New England Journal of Medicine. They sound a note of caution for one of biotechnology’s hottest subsectors, where companies like Spark Therapeutics Inc. are developing treatments to repair genetic defects that cause disease. The researchers and companies crafting gene therapies need to work together to ensure the best methods are used, especially given the small number of patients who may benefit, investigators said.
During the Penn procedures, a corrected copy of the gene that makes a protein crucial for vision is injected into one eye. An in-depth examination of three early patients found that their eyesight improved in the treated eye for as much as three years. After that, the benefit started to trail off, and the patients lost critical photoreceptor cells in the retina at the same pace as in their untreated eyes.
While researchers are disappointed they don’t have a one- time treatment, the study results are an “opportunity to improve the therapy so that the restored vision can be sustained for longer durations in patients,” said Samuel Jacobson, the lead researcher of the trial and a professor at Penn’s Scheie Eye Institute in Philadelphia.
The university researchers didn’t use the same treatment as Philadelphia-based Spark to treat the condition, which is known as Leber congenital amaurosis.
Spark went public in January and is valued at about US$1.4 billion (RM5.03 billion). Its product is now in the third and final stage of clinical trials before regulatory approval. The company has been following patients in earlier trials for two to four years and their vision improvements have lasted, said Chief Executive Officer Jeffrey Marrazzo.
“All these products are very different,” Marrazzo said in a telephone interview. “On the surface, they may look similar because they are all called gene therapy, but there’s a tremendous amount of devil in the details.” The various gene therapy approaches all use slightly different doses, components in the therapy and delivery methods.
Not Perfect Yet
In the Penn trial, the patients seemed to have better vision after treatment than before, even though the sensitivity had declined from peak levels.
“It would be foolish to think we could get the treatment perfectly right in the first studies,” said Eric Pierce, director of the retinal degenerations service at Massachusetts Eye and Ear in Boston. Pierce worked on an early Spark trial and hasn’t been involved with any of the studies since.
“Maybe the people got treated too late in the disease course and the cells were already destined to die,” Pierce said. “Or maybe we didn’t have the dose of the gene therapy quite right yet. My expectation is with the right dose in the right setting, we would prevent further retinal cell loss. To me the most important message is we need to continue to improve these therapies.”
Between 90,000 and 180,000 people worldwide have Leber congenital amaurosis, a degenerative disease of the retina, the light-sensitive tissue at the back of the eye where images focus and are converted into electrical signals that are read by the brain. A mutation that leads to loss of function in the RPE65 gene is responsible for the disease in about 400 Americans and 9,000 people worldwide, Pierce said. That subset could benefit from the gene therapy. — Bloomberg