Updated: Mar 7, 2020
Scientists enabled the gene-editing technique called CRISPR to customize a gene regardless whether the DNA is still inside individual’s system.
A new procedure necessitates injecting the microscopic gene-editing tool into the eye of a patient impaired by any kind of genetic disorder to make the patient see again. It is expected that in a matter of weeks the success of procedure will come clear and in 2 or 3 moths – they hope to know within weeks whether the approach is working and whether the full vision capability can be restored.
Dr. Eric Pierce, a professor of ophthalmology at Harvard Medical School and director of the Inherited Retinal Disorders Service at Massachusetts Eye and Ear is leading the project launched: "We're helping open, potentially, an era of gene-editing for therapeutic use that could have impact in many aspects of medicine".
The CRISPR technique’s key differential factor is easing the customization of the genetic code, simultaneously promising to cure multiple types of diseases.
Previously, doctors used CRISPR to treat patients diagnosed with cancer and certain blood disorders such as sickle cell anemia or beta-thalassemia. Here, doctors removed cells from patients' bodies, edited genes in the cells with CRISPR in the lab and then infused the modified cells back into the volunteers' bodies to either attack their cancer or produce a protein their bodies are missing. However, despite the results, it is complicated to claim that future strategies connected with further implementation of the method would be equally successful.
Nevertheless, as part of the new experiment, doctors at the Casey Eye Institute in Portland injected (into the eye of a patient who is nearly blind from a condition called Leber congenital amaurosis) microscopic droplets carrying a harmless, previously engineered virus to deliver the instructions based on the CRISPR gene-editing machinery.
Whilst in infancy, the rare genetic condition destroys light-sensing cells in the retina that are necessary for vision. Vision impairment with LCA varies, but most patients are able to distinguish between light and dark and detect some movement. "The majority of people affected by this disease have the most severe end of the spectrum, in terms of how poor their vision is. They’re functionally blind." – as noted by Dr. Pierce.
Once the virus carrying the CRISPR instructions was injected into the eye, the gene-editing tool will extirpate the genetic defect that caused the blindness. The researchers believe it would restore production of a crucial protein and prevent the death of retina cells and revive other cells — enabling patients to regain at least some vision. "It's the first time the CRISPR gene-editing is used directly in a patient," Dr. Pierce says. "We're really optimistic that this has a good chance of being effective."
The study is being sponsored by Editas Medicine, of Cambridge, Mass., and Allergan, based in Dublin. They plant to include 18 patients, some as young as ages 3 to 17, who will receive three different doses.
"We're very excited about this. This is the first time we're doing editing inside the body," says Charles Albright, the chief scientific officer at Editas.
"We believe that the ability to edit inside the body is going to open entire new areas of medicine and lead to a whole new class of therapies for diseases that are not treatable any other way," Albright says.
Francis Collins, director of the National Institutes of Health, calls the advance "a significant moment”: "All of us dream that a time might be coming where we could apply this approach for thousands of diseases. This is the first time that's being tried in a human being. And it gives us hope that we could extend that to lots of other diseases — if it works and if it's safe."
It is important to note that both Pierce and Albright stressed that only one patient has been treated so far. At this stage, this study is designed primarily to determine whether injecting the gene-editing tool directly into the eye is safe.
The researchers are starting with lowest dose and the oldest patients, whose vision was severely damaged and doctors are only treating one eye in each patient. All of those steps are being taken in case the treatment is unsuccessful, perhaps even causing more damage instead of being helpful.
"CRISPR has never been used directly inside a patient before," Dr. Pierce says. "We want to make sure we're doing it right.". Nevertheless, Pierce acknowledged that if the underlying defect can be repaired in this patient and others with advanced damage, they “have the potential to restore vision to people who never had normal vision before”.
The study also involves a form of Leber congenital amaurosis known as Type 10, which is caused by a defect in the CEP290 gene.
If the approach appears to be safe and effective, the researchers will start treating younger patients.
"We believe children have the potential to have the most benefit from their therapy, because we know their visual pathways are still intact," Albright explains.
Additionally, an hour-long procedure involves making tiny incisions that enable access to the back of the eye. That allows a surgeon to inject three droplets of fluid containing billions of copies of the virus that has been engineered to carry the CRISPR gene-editing instructions under the retina.
To tackle this issue, the CRISPR editing elements would snip out the mutation that causes a defect in CEP290. The hope is that this would be a one-time treatment that would correct vision for the rest of a patient’s life. If it works, the volunteers in the study might be able to have the procedure repeated on the other eye later.
"If we can do this safely, that opens the possibility to treat many other diseases where it's not possible to remove the cells from the body and do the treatment outside," Dr. Pierce says. The list of such conditions includes some brain disorders, e.g. Huntington's disease and inherited forms of dementia, as well as muscle diseases, e.g. muscular dystrophy and myotonic dystrophy.
"Inherited retinal diseases are a good choice in terms of gene-based therapies," says Artur Cideciyan, a professor of ophthalmology at the University of Pennsylvania, given that the retina is easily accessible.
But Cideciyan cautions that other approaches for these conditions are also showing promise, and it remains unclear which will turn out to be the best.
"The gene-editing approach is hypothesized to be a 'forever fix,' " he says. "However, that's not known. And the data will have to be evaluated to see the durability of that. We'll have to see what happens."