CRISPR Cured her Sickle Cell Disease. What Else Does It Have in Store?

Medscape reported that when Victoria Gray was three months old, her family was told to keep her close: her prognosis wasn’t looking good. She had been rushed to the ER after her grandmother had noticed her writhing in pain during bath time one evening.
There, the Gray family learned their infant would spend a lifetime with the painful genetic condition, sickle cell disease (SCD). The condition’s characteristic unshapely red blood cells can cause strokes and heart attacks even in the youngest of patients. Her doctor’s expected their daughter wouldn’t make it past her 6th birthday.
 
For Gray, her 34 years since had been defined by the pain and limitations that come with SCD. But after living in a constant shuffle between managing pain crises, doctor’s appointments, blood transfusions, and trips to the ER, Gray decided to change her story.
In 2019, she bit the bullet of uncertainty, and became the first patient to be treated with SCD using CRISPR, the groundbreaking gene-editing technology that precisely edits a person’s genes to correct for mutations and malfunctions.
 
Today, she lives a very different life.

Sickle Cell Disease

Sickle cell disease is a umbrella term for a group of disorders that cause red blood cells to be unwieldy, in a sickle or crescent-like shape. These crescent-shaped red blood cells have sharp and sticky edges which jam into the walls of the blood vessels, tearing the lining and disrupting blood flow as they get blocked up in the passages. This damage can provoke potentially life threatening symptoms. It also causes patients to experience excruciating pain called a ‘pain crisis’, as well as fatigue, jaundice, and stunted growth. During childhood, patients only experience symptoms during pain crises. However, with age, symptoms are felt round the clock.
 
The disorder can be diagnosed with blood tests. It is a genetic disease most common in people of African descent. In order to inherit the disease, both parents must carry the gene. The recessive trait is believed to be protective against severe malaria. There are symptomatic treatments including pain relief, antibiotics, and blood transfusions, as well as blood and bone transfusions for more severe cases. There is no cure.

The Novel CRISPR

CRISPR though first conceptualized in the 90’s, needed a couple decades of work before the novel technology was ready to work its magic. The technology is able to get to the roots of many conditions which are genetic in nature.
Using CRISPR, researchers create a genetically modified virus that is coded with the enzyme ‘Cas9’, that is coded to target the harmful genetic coding. The new cells enter a person’s body, and can then edit a person’s genes by deleting and rewriting sections of DNA to correct for mutations and malfunctions.
 In 2020, Doudna and Emmanuelle Charpentier’s work on the transformational gene-editing technology CRISPR won them the Nobel Prize for Chemistry in 2020 for their progress towards “rewriting the code of life.”
The technology is opening up the world of genetic tinkering. With the keys to our characteristics and growth in the hands of scientists, the community expects CRISPR will eventually end a wide range of rare diseases.

 The Ethics

However, the technology comes with great potential and a slew of ethical questions. They expect it could be harnessed to eliminate cystic fibrosis, Down syndrome, blindness, dyslexia, and a range of other genetic conditions. Theoretically it could even edit the genes of an embryo, tinkering with a fetus’s core characteristics.
“It allows you to alter the blueprint of life for any organism you want,” said Dr. Eric Olson, a molecular biologist who’s developing CRISPR treatments for muscular dystrophy at the University of Texas. “You can’t really overstate the potential long-term impact of this technology on life as we know it.”
Theoretically, it could be used to customize physical and mental traits too, including selecting a child’s eye color or turning up their IQ.
Already the technology is being tested on animals and cells, creating goats that are fluffier and curvier to make for more wool and thicker meat. It’s been used to create bacteria that protects yogurt and cheese from viruses, and in 2018 a pair of twins in China that had their embryos altered to prevent them from a life with HIV. This use was seen as an overstep, with outrage from the science community. That doctor was sentenced to three years in prison, and sparked a wave of prohibitions and limitations on the technology before more ethical questions are worked through.
Insoo Hyun, PhD and director of research ethics at the Center for Bioethics at Harvard Medical School explained,
“One ethical question to ask in research is, who bears the risks and benefits of a new technology? In the case of germline editing, the benefit may be for the couple, but the risks befall the unborn, and possibly their descendants.”

A Rare Disease CRISPR Success

Morning Edition reported on the first patient that have been treated with CRISPR in groundbreaking studies to restore vision. 54-year-old Carlene Knight and Michael Kalberer, 43, are the first two patients to receive a novel CRISPR solution that can remedy inherited blindness caused by their chronic genetic condition, Leber congenital amaurosis, allowing the patients to see for the first time in their lives.
 
Knight and Kalberer are the first to receive this novel gene-editing technique, which unlike SCD, edits the genes from inside the body, rather than first tinkering with the cells in the lab before they’re infused back into the body. Since retinal cells are excessively fragile, the doctor’s instead applied this therapy in tiny incisions of a billions of copies tiny genetically modified virus into the eyes. These CPISPR cells act like a tiny surgeon, combing through the cells and removing the mutation. This enables the production of a protein which restores the vision.
 
 
“No one had ever done direct treatment of gene-editing inside the human body,” explained Dr. Lisa Michaels, the chief medical officer at Edits Medicine, the sponsor of the vision study. “And as a consequence, there [were] a lot of concerns whether by taking these patients who have limited vision we might have had risks such as disturbing the vision and even loss of the little bit they had.”

Gray’s Pain Relents

Gray had been on an unsuccessful quest for a bone marrow transplant, which, though risky, was her only option. A life with SCD meant unrelenting pain and medical necessities. When Gray was given the option to dramatically change her life-chances, as one of the first people in the world to be treated with the novel gene editing technique: she took it without hesitation.
“I said, ‘We don’t know for sure if it will work,’ “ said Dr. Haydar Frangoul, Gray’s doctor and medical director of pediatric hematology at Sarah Cannon Research Institute. “She said, ‘Sign me up.’”
 
In 2019, Gray began treatment, when a team of doctors took billions of her stem cells to be modified in a lab in Europe. The injection sent a new set of cells into her veins, that now could produce the healthy form of hemoglobin that she’s been needing.
Two years down the road, Gray is adjusting from a routine when blood transfusions were unremarkable. Now, a life without constant medical needs is grounds for joy. For Gray, the new mundanity brings her great pleasure.
Gray said,
“I can do things for myself and for my family that I couldn’t before, like see my daughter cheerleading, go to my son’s football games, and just live and enjoy life. I now have hope.”

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