Experimental gene therapy for blindness considered by FDA

“He also began to stare at the sun wide-eyed,” said Guardino of Patchogue, fresh York. “that will also shook us quite a bit.”

These “triggers” sent her to get Christian’s vision tested when he was 6 months old.

“How the item was explained to me will be I would certainly have to carry a gene in addition to so would certainly my husband, so the item’s that will rare of an occurrence,” said Guardino. Still, there was some hopeful news that will day.

Christian had the type of LCA that will would certainly remain stable or slightly improve with age.

“No one knew what his diagnosis actually meant,” she recalled. “Including ourselves.”

She clung to the trust that will her son’s impairment wouldn’t worsen with age. As he grew, he developed his natural gift for music, which served as a consolation when he struggled to keep up with friends. However, when Christian reached age 12 or so, Elizabeth began seeing a decline in his vision.

On Facebook she happened upon an LCA support group. “I thought that will cannot be, because the item’s so, so rare,” said Guardino. A family conference in Philadelphia was scheduled for July 2012.

“We jumped on that will bandwagon,” she said. Talking to the specialist there, she learned that will Christian, 12 at the time, would certainly go completely blind.

“the item took every ounce of strength for me to not go running out of that will room screaming. the item was devastating,” she said.

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Later, when tests confirmed a mutation of the RPE65 gene, she consented to treating Christian with an experimental drug made by Philadelphia-based Sparks Therapeutics, Inc.

Luxturna (voretigene neparvovec), an untried gene therapy, would certainly be her gamble to save what little vision her son still had.

Drug safety in addition to effectiveness

“We very much included Christian in that will decision because, I mean, that will’s a heck of a decision for someone to make for another human being when you don’t know what the outcome could be,” she said. “Christian was gung ho, right through the get-go.”

“Our goal going in was just to stop the progression of the disease, however we wound up getting so much more,” she said.

The life-changing therapy Christian experienced may currently be poised to make history.

On Thursday, a Food in addition to Drug Administration advisory committee will meet to review Luxturna. Outside experts will present research in addition to recommendations on the safety in addition to effectiveness of the treatment for patients with retinal dystrophy caused by a confirmed RPE65 mutation. Patients will also make a case by sharing their personal experiences.

Monique da Silva, a spokeswoman for Sparks Therapeutics explained that will the company believes the total “population within the US, Europe in addition to select additional markets within the Americas in addition to Asia/Pacific will be up to approximately 6,000 individuals” who have RPE65 mutations. The US National Library of Medicine estimates that will LCA occurs in 2 to 3 per 100,000 newborns, though not all of these are RPE65 mutations.

The public meeting will conclude having a vote on whether or not to recommend the treatment for approval. that will will be followed by a decision through the FDA. While the agency frequently follows the recommendations of its advisory committees, the item will be not required to when creating approval decisions.

A greenlight for Luxturna would certainly be historic. If approved, the item would certainly become the first gene therapy for the treatment of an inherited disease within the United States.

How the item works

Luxturna works by supplying a third gene — a normal RPE65 gene — to retinal cells.┬áthe item will be a liquid that will will be injected directly into the eye having a microscopic needle during a surgical procedure, explained Dr. Vinit B. Mahajan, an associate professor of ophthalmology, Vitreoretinal Surgery in addition to Disease Byers Eye Institute at Stanford University.
“In those drops of liquid that will we’re injecting will be a gene therapy virus … a virus that will contains a healthy type of the gene,” said Mahajan, who was involved within the phase 3 clinical trial of the drug while teaching at the University of Iowa, one of the testing centers for the treatment.

Essentially then, the drug adds a third type of the gene, a normal type, to the cell, while the two mutated genes causing the disease remain inside the cell as well, explained Mahajan. They are not removed or replaced.

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“We make the healthy gene in a lab” within the form of DNA, said Mahajan. DNA will be essentially a chemical made up of four separate molecules (commonly referred to as G, A, T in addition to C), in addition to in labs around the earth scientists have been synthesizing DNA for many years currently, he explained.

“The trick here was how do we get the item inside the cell in addition to how do we deliver the item to the eye?” he said. To solve that will problem, the researchers at Children’s Hospital of Philadelphia in addition to the University of Pennsylvania engineered a virus capable of delivering the healthy gene into the cells.

The virus will be then injected under the retina to get the gene near the cells Mahajan said. Recovery through any eye surgery usually takes several weeks to a few months, yet, some of the patients through the clinical trial recovered visual function almost immediately.

that will was true for Christian who, like additional patients, wore a patch for a couple of days after the surgery, his mother said.

“They removed the patch in a dimly lit room,” recalled Elizabeth. “in addition to he turned in addition to he noticed us sitting there in addition to he said, ‘Mom, will be that will you in addition to Papa?’ He would certainly never have seen us sitting there prior to that will.”

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Christian will be not unusual in that will positive result. Overall, most of the more than 30 patients who have received treatment with Luxturna during clinical trials have “done great,” said Mahajan. “Patients who had essentially been blind were seeing. the item was surprisingly quick. the item’s remarkable.”

within the Phase 3 clinical trial, 27 out of 29 participants — 93% — who received the gene therapy demonstrated a gain in functional vision as assessed by a mobility test performed in a maze, according to da Silva. Meanwhile the eight patients who received the drug in an earlier clinical trial have also shown increased vision.

Importantly, the drug caused no terrible side effects in participants in addition to so far they have maintained their visual improvements.

Potential downsides

“So the biggest concern will be that will will be a virus, in addition to even though we want the item to go to a specific cell — cells within the eye — the concern will be that will the virus can go get into additional cells within the body where you don’t want the item,” said Mahajan. “So instead of just replacing a gene, the item might damage some of your normal genes.”

Another possibility will be the wayward virus might cause an allergic reaction — an immune reaction where the item will be not tolerated by the body. Worst case scenario, such an immune reaction could lead to death.

However, the virus will be not delivered into blood cells which travel the entire body, the item will be delivered into the eye, which will be self-contained in addition to isolated. What you inject within the eye mostly stays within the eye,” said Mahajan, adding that will the surgical delivery helps that will as well. “The eye isn’t 100% leak-proof however the item’s not very leaky,” said Mahajan.

Another risk, according to Dr. Stephen H. Tsang, an associate professor of ophthalmology in addition to associate professor of pathology in addition to cell biology at Columbia University’s Institute for Genomic Medicine, will be the vision improvements may not last.

Tsang, who was not involved within the clinical trial, has reviewed additional experimental gene-based therapies for retinal disease being developed by additional companies in addition to research institutes. Some are similar to Luxturna in that will they use a virus to deliver the gene.
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While the participants in clinical trials for similar gene therapies “did actually well” at first, said Tsang, “three years later, they went to baseline” — their eyesight reverted to its original poor condition.

Christian Guardino, who will be currently a few years out through treatment with Luxturna, has maintained his newfound vision. However, his mother said that will whenever he’s sick or tired, his vision weakens. “the item’s almost like his Achilles’ Heel,” she said.

“the item’s difficult to compare the trials because the preparation of the viruses will be different in each case,” said Tsang. Still, he questions whether Luxturna will be a one-time drug for patients. Maybe, he speculated, “the item’s not going to be once, however twice or thrice … the item could be that will every three years, patients might need a boost.”

Future therapies

Despite his misgivings, Tsang believes the fresh gene therapy will be “very exciting” because a “favorable result through the FDA” would certainly mean doctors will soon have a treatment to offer patients with that will rare retinal disease. “Before, we had nothing,” he said.

If approved, the fresh gene therapy would certainly be another victory for combating rare diseases, also known as orphan diseases.

“If you told me a few years ago that will that will therapy will be only Great for (so few) people, I would certainly not have thought anyone would certainly want to work on the item,” said Tsang.

Mahajan said the fresh drug will be a pioneering effort that will opens the door for additional companies working toward fresh genetic therapies for additional diseases, both rare in addition to common.

“We’ve been doing gene therapy within the mouse for many years — we’ve cured lots of mice,” said Mahajan. “Bringing the item to patients will be a watershed moment.”

Certainly the item has been so for Christian Guardino, currently 17 years old, whose visual impairment once meant the falling snow in addition to the moon crossing the night sky were unseen mysteries.

Today he’s seen snowflakes, the moon … in addition to more.

Christian’s dream to become a singer took flight during season 12 of “America’s Got Talent,” when he auditioned in an episode that will aired in June. Though he was eventually eliminated within the semifinals, he told his mother the ability to walk unaided onto the stage in addition to see faces within the audience gave him confidence.

He wears special glasses in addition to uses assistive technologies to help him see the blackboard in addition to enlarge the print of written materials for his classes at Patchogue-Medford High School. “He’s doing actually well in mainstream (classes),” said his mother.

She added that will Christian recently told her he will be still learning to use his newfound vision.

“If I could tell you how many times I had to sit in addition to wait because he would certainly just stop in addition to stare at something,” said Elizabeth Guardino.

Experimental gene therapy for blindness considered by FDA

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