.-') _ .-') _ | |
( OO ) ) ( OO ) ) | |
.-----. ,--./ ,--,' ,--./ ,--,' | |
' .--./ | \ | |\ | \ | |\ | |
| |('-. | \| | )| \| | ) | |
/_) |OO )| . |/ | . |/ | |
|| |`-'| | |\ | | |\ | | |
(_' '--'\ | | \ | | | \ | | |
`-----' `--' `--' `--' `--' | |
lite.cnn.com - on gopher - inofficial | |
ARTICLE VIEW: | |
Experimental gene therapy restores some vision in patients with | |
inherited blindness | |
By Jacqueline Howard, CNN | |
Updated: | |
10:32 AM EDT, Mon May 6, 2024 | |
Source: CNN | |
For her entire life, college student Olivia Cook had only a small | |
degree of central vision. It was as if she was watching the world | |
through a straw hole, and in dimly lit places, she could not make out | |
people’s faces, only their silhouettes. | |
But after receiving an experimental gene-editing treatment to one of | |
her eyes, she now can see things she never saw before. | |
Cook was born with an inherited retinal disorder that causes blindness, | |
a rare type of eye disorder historically called Leber congenital | |
amaurosis or LCA. A few years ago, she decided to participate in a | |
clinical trial that involved using the gene-editing tool CRISPR to | |
correct the form of inherited blindness that she has. | |
“My life has mostly changed in terms of being hopeful that there is | |
going to be more science and findings in the future,” said Cook, 22, | |
who is currently studying marketing and product development at Missouri | |
State University in Springfield. She received the experimental | |
gene-editing treatment through a surgery performed on her left eye. | |
“Now, post-surgery and post recovery, I am able to see in dimmer | |
lighting with my left eye,” Cook said. | |
A treatment that used CRISPR was found to be safe and efficacious in | |
improving vision among a small sample of patients with inherited | |
blindness in the Phase 1/2 clinical trial that Cook participated in. | |
Inherited retinal degenerations are a leading cause of blindness around | |
the world. | |
Among a total of 14 volunteers, including Cook, the gene-editing tool | |
was found to be associated with a “meaningful improvement” in | |
vision for most patients around three months later and it was not | |
directly tied to any serious side effects, according to the trial | |
results, published Monday in the New England Journal of Medicine. The | |
therapy remains experimental and the results need to be replicated in a | |
larger group of people. | |
Months following the treatment, Cook was sitting with friends on a | |
balcony that had Christmas lights wrapped around the railing. It was | |
dusk, she recalled, yet she could see her friends’ faces glow under | |
the twinkling Christmas lights. She was shocked. | |
“With my right eye, I was not able to see their facial features. I | |
was only able to see their silhouette. With my left eye, I could see | |
everything on their face – so, significant difference, especially in | |
the dim lighting,” Cook said about that evening. | |
“One of the biggest ‘aha moments’ that I had was I had been | |
talking to my mom one day after the surgery – it was about six to | |
nine months after the surgery when I noticed most of my improvement,” | |
Cook said. | |
“I could see a candle flickering behind me, which I’ve never seen | |
that before,” she said. “I’d never picked up anything from over | |
there before with the peripheral.” | |
Before the treatment, Cook said that she sometimes could conceal the | |
vision challenges she has had. Her limited vision often was an | |
internal struggle. | |
“You wouldn’t really know that my eyesight is terrible until you | |
spend a significant amount of time with me,” Cook said. “If we saw | |
each other in the street, if I introduced myself to you, you’d never | |
know.” | |
But now, she is no longer hiding. | |
A groundbreaking ‘proof of concept’ | |
This study is the first time that CRISPR has been used in the eyes of | |
living people. | |
“The results of this study provide proof of concept that CRISPR-Cas9 | |
gene editing can be used safely and effectively to treat inherited | |
retinal disorders,” said the study’s first author Dr. Eric Pierce, | |
director of the Ocular Genomics Institute at Mass Eye and Ear and | |
Harvard Medical School. | |
The trial was funded by the biotechnology company Editas Medicine and | |
conducted in the United States by researchers at Mass Eye and Ear of | |
the Mass General Brigham health care system and other US-based | |
institutions, including the Perelman School of Medicine at the | |
University of Pennsylvania, the University of Michigan, the University | |
of Miami, and Oregon Health & Science University. | |
“We’re really hopeful that CRISPR-Cas9 gene editing technologies | |
will now be applied to other genetic forms of inherited blindness, and | |
indeed other genetic diseases in general,” Pierce said. “We’re | |
hoping this will help open the era of therapeutic use of CRISPR-Cas9 | |
technologies.” | |
The trial, which started in 2019, enrolled 12 adults, ages 17 to 63, | |
and two children, ages 9 and 14, with inherited retinal degeneration | |
caused by mutations in the . That gene provides instructions for making | |
a protein involved in many types of cells, including light receptor | |
cells in the eyes. Mutations in CEP290 are the most common cause of | |
severe early-onset retinal degeneration, which causes vision loss in | |
children. | |
Currently, there is no treatment approved by the US Food and Drug | |
Administration for CEP290-associated inherited retinal degeneration. | |
These patients would not be able to read any lines of letters or | |
numbers on a vision chart that most people receive at the eye doctor, | |
and visual impairment may worsen over time. | |
For the trial, the 14 participants underwent a surgical procedure in | |
which a drug called EDIT-101 that encodes the CRISPR gene-editing | |
components was injected under the retina of one of their eyes. Since | |
the trial was conducted to primarily evaluate safety and efficacy, only | |
one eye in each patient was studied. | |
“The subjects get an injection of the gene-editing drug, which is | |
called EDIT-101, under their retina,” Pierce said. “That drug | |
encodes the CRISPR-Cas9 gene-editing machinery, and once that starts | |
working inside the retinal cells of those patients, it cuts out the | |
mutation in CEP290 from the genome of their retinal cells, allowing the | |
function of the CEP290 gene to be restored.” | |
When the first patients in the study were treated in 2020, it was the | |
directly into the living human body. | |
Among the adult volunteers, two were given a low dose of the | |
medication, five were given an intermediate dose and five were given a | |
high dose. Both of the children in the study were given the | |
intermediate dose. The outpatient procedure took around an hour and a | |
half. | |
The patients were then monitored every three months for a year and then | |
less frequent monitoring continued for two years. In these follow-up | |
visits, they underwent a series of vision tests among other | |
evaluations. | |
The researchers found that 11 patients in the study had some type of | |
improvement in their vision following the CRISPR therapy, and these | |
improvements occurred about three months after the procedure and were | |
sustained during subsequent visits. | |
Also, no serious side effects occurred in response to the treatment at | |
any of the dose sizes, according to the researchers, and the adverse | |
events that did occur were mild or moderate. There were also no signs | |
that the CRISPR gene-editing caused ripple-effect harm to the genomes | |
of the patients. | |
“The primary goal of this first in-human study was to test the safety | |
of using CRISPR-Cas9 gene editing in vivo. When we started the trials, | |
the subjects who were treated were the first patients ever to have | |
received CRISPR-Cas9 gene-editing treatments in vivo,” Pierce said. | |
“There were no serious adverse events related to the treatment, or | |
the surgery required to deliver the treatment and no dose-limiting | |
toxicities.” | |
Following the surgery, one patient experienced some bleeding in the | |
eye, impairing their vision, but that has since resolved, according to | |
the researchers. | |
“Once that hemorrhage cleared, the subject’s vision returned to | |
baseline,” Pierce said. | |
Another patient experienced vision impairment associated with small | |
mounds observed under their retina six months after the procedure. | |
These types of hyperreflective mounds have been seen in other studies | |
involving subretinal gene therapies, the researchers noted, and the | |
cause of them is not clear. | |
“It’s thought to be inflammation,” Pierce said about the mounds. | |
The patient was treated with a course of steroid medicines, according | |
to the study, and their recovery is ongoing. | |
“As the mounds resolved their vision also improved,” Pierce said. | |
“I think this drug was as safe as possible in terms of design.” | |
‘It’s not a panacea’ | |
Complete vision has not been restored among the patients. Most in the | |
trial could not read any line of an eye chart prior to the study, and | |
only four of them experienced some improvements in this ability. But | |
some patients reported, after receiving treatment, being able to see | |
their cell phones light up, differentiate various foods on their dinner | |
plates, identify the spinning Apple icon on a computer screen or even | |
noticing vibrant sunsets. | |
“I started to see what are described as bursts of color,” said | |
Michael Kalberer, 46, who and first noticed improvements in his vision | |
about two to six months later. He started the study in 2020. | |
“It was a pretty cool moment to see strobe lights on the dance floor | |
of my cousin’s wedding change color,” said Kalberer, who added that | |
if he had not received the treatment, all he would have seen on the | |
dance floor would have been shadows and flickering lights, and he would | |
not have been able to identify the colors. | |
Kalberer described the CRISPR treatment as “groundbreaking,” but | |
warned it’s not a cure. | |
“It’s not a panacea,” said Kalberer, who still can’t see | |
standard text or photos on a screen. “My disease is still here. | |
It’s not gone. I’m not cured. … But it definitely slowed the | |
progression of it.” | |
Pierce said that he hopes this approach to using CRISPR as a therapy | |
for inherited blindness can be studied again in a larger and more | |
diverse group of patients. All of the Phase 1/2 trial participants were | |
non-Hispanic and White. | |
In 2022, further studying CRISPR gene editing as a therapeutic approach | |
for CEP290-associated inherited blindness and instead of conducting | |
further trials, has continued to follow-up with the patients who have | |
been treated to date. | |
The latest results from the Phase 1/2 trial support moving forward with | |
a Phase 3 trial and then ultimately registering the therapy for | |
possible FDA approval, Pierce said. | |
“We are working with Editas to identify an additional commercial | |
partner for Phase 3 studies. We’re actually hoping this publication | |
will stimulate interest in the biotech and pharma communities about | |
that,” Pierce said. | |
More research over time could shed light on the long-term effects of | |
the CRISPR-Cas9 gene editing tools, which, now that they have been | |
injected into patients, will be present in patients for the rest of | |
their lives, Pierce said. | |
“I think the real risk that we’re all concerned about with | |
CRISPR-Cas9 gene editing is: Could the gene editing machinery that | |
we’ve introduced into the retinal cells of these patients do | |
something else, somewhere else in the genome, in addition to the | |
therapeutic activities that it was designed for?” Pierce said. | |
“Could a cut in the genome be made 10 years from now, that could have | |
an adverse effect over time? I think the answer to that is yes, it | |
could. But we’re hopeful that risk is very low,” Pierce said. | |
“That’s what we need additional follow-up for.” | |
‘Quality of life matters’ | |
The results from the Phase 1/2 trial — and how patients experienced | |
some improvements in vision — are a valuable reminder of how | |
important quality of life can be for patients, said Art Caplan, a � | |
and founding head of the Division of Medical Ethics at NYU Grossman | |
School of Medicine’s Department of Population Health. | |
“Usually when we’re doing gene therapies or other innovative | |
interventions, we associate them with saving lives. This experiment is | |
a huge reminder that quality of life matters. This is about vision,” | |
Caplan said. “No one’s dying. No one’s saved. But restoration of | |
vision is an important achievement, and it’s a reminder that quality | |
of life has to be factored into what we decide to cover in terms of | |
insurance, reimbursement and what we try to study.” | |
He agreed with the researchers that more safety data over time would be | |
helpful. | |
“They haven’t really had these subjects that long with the | |
intervention to guarantee long-term safety,” Caplan said. “For | |
these kinds of genetic interventions, you have to follow them over long | |
periods of time — years — to make sure that other genes weren’t | |
impacted.” | |
These new Phase 1/2 trial results provide a “building block” for | |
scientists to work off of in the future when developing gene therapies | |
to treat eye disorders, said Dr. Vlad Diaconita, a retinal surgeon and | |
assistant professor of ophthalmology at Columbia University Vagelos | |
College of Physicians and Surgeons. He was not involved in the trial. | |
“Does this apply to the American population at large? Not right | |
now,” Diaconita said about the experimental treatment. | |
“It does, however, apply to the thousands of kids born in future | |
years that have this particular genetic subtype. So yes, an approval of | |
this particular gene delivery could benefit people over time,” he | |
said. “It’s a proof of concept that seems to be moving us in the | |
right direction.” | |
Diaconita’s colleague Dr. Aliaa Abdelhakim called this | |
proof-of-concept study “groundbreaking” in the sense that it shows | |
the treatment approach can be safe and result in some improvement for | |
patients, but more research is needed on a larger scale to determine� | |
what kind of patients will benefit in the long term, and how long those | |
improvements may last. | |
“We still have to wait a little longer to see if this pans out in the | |
long-term,” said Abdelhakim, an ophthalmologist-geneticist, retina | |
specialist and assistant professor of ophthalmology at Columbia | |
University Vagelos College of Physicians and Surgeons. She also was not | |
involved in the trial. | |
“We don’t know if improvements from this treatment are going to | |
be sustained. Is their vision going to stay improved throughout their | |
lives?” she asked. “The reason this is important is because this is | |
the first time CRISPR has been used in this way, in the eye.” | |
<- back to index |