via Ash Image Bank
This blood smear shows sickle cell disease.
University of Illinois Chicago is one of the U.S. sites participating in clinical trials to cure severe red blood congenital diseases such as sickle cell anemia or Thalassemia by safely modifying the DNA of patients’ blood cells.
The first cases treated with this approach were recently published in an article co-authored by Dr. Damiano Rondelli, the Michael Reese Professor of Hematology at the UIC College of Medicine. The article reports two patients have been cured of beta thalassemia and sickle cell disease after their own genes were edited with CRISPR-Cas9 technology. The two researchers who invented this technology received the Nobel Prize in Chemistry in 2020.
In the paper published in the New England Journal of Medicine, CRISPR-Cas9 Gene Editing for Sickle Cell Disease and ?-Thalassemia, researchers reported gene editing modified the DNA of stem cells by deleting the gene BCL11A, the gene responsible for suppressing fetal hemoglobin production. By doing so, stem cells start producing fetal hemoglobin so that patients with congenital hemoglobin defects (beta thalassemia or sickle cell disease) make enough fetal hemoglobin to overcome the effect of the defective hemoglobin that causes their disease.
The advantage of this approach is that it uses the patient’s cells with no need for a donor. Also, the gene manipulation does not use a viral vector as with other gene therapy studies but is done with electroporation (quick production of pores into the cells with high voltage) which is known to have low risk of off-target gene activation, according to Rondelli.
Sickle cell disease is an inherited defect of the hemoglobin that causes the red blood cells to become crescent-shaped. These cells can lyse and obstruct small blood vessels, depriving the body’s tissues of oxygen. The disease can cause extreme pain and damage the lungs, heart, kidneys and liver. Beta thalassemia is a blood disorder that reduces the production of hemoglobin — the iron-containing protein in red blood cells that carries oxygen to cells throughout the body. In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body.
The first two patients to receive the treatment have had successful results and continue to be monitored. Rondelli is on the steering committee for an international clinical trial, with UIC being the only site in Chicago. Although the trial is at an early stage and the first patients will be followed for some time before expanding the numbers worldwide, UIC will be among the few sites ready for this treatment.
“It is a great privilege for UIC to be part of this international study and I hope that in the future we will have our own patients undergo this procedure,” Rondelli said.
“UIC and UI Health is an ideal place for any cellular therapy in sickle cell disease because of our experience and success in stem cell transplantation in these patients. In fact, over 75% of sickle cell patients can be cured with a transplant, and we have already done over 50 cases,” he said.
While a full-match donor is still the first line of treatment, finding a compatible stem cell donor is challenging. For this reason, many centers including UI health have developed strategies to successfully utilize donors who are only 50% compatible, called haploidentical donors. However, according to Rondelli, in about 30% to 50% of the patients, there are still multiple barriers that can limit the possibility of a donor-derived transplant, such as a family donor availability, or the presence of antibodies in the patient caused by many prior red cell transfusions, that would reject the donor stem cells.
“This gene-editing procedure has the potential to overcome all of these. Cells of the same patient can be manipulated and can be transplanted without the risk of rejection or to cause immune reactions from the donor (graft-versus-host disease),” said Rondelli. “For the almost 900 patients with SC coming to our hospital, this should be great news.”
Patients who in the future will participate in the trial will have cells sent to the CRISPR manufacturing site where the cells undergo genetic editing. Patients then receive chemotherapy prior to the edited stem cells being re-inserted into their bloodstream.
Researchers hope this treatment can be a game-changer for world health. Sickle cell disease and beta thalassemia and other congenital blood disorders are major diseases in the world. Rondelli said 5 million people only in Nigeria suffer from sickle cell disease, and many others in Africa. Also, currently, 30% of transplants being performed in India, which has 1.3 billion people, are to treat severe beta thalassemia, he added.
“The hope is that this treatment will be accessible and affordable in many low-middle-income countries the Middle East, Africa, and India, and have an important impact in the lives of many people in these areas,” said Rondelli.
The Latest Updates from Bing News & Google News
Go deeper with Bing News on:
Sickle cell disease
- Exa-Cel Eliminates Vaso-Occlusive Crises in Most Sickle Cell Patients
For almost all patients with sickle cell disease, treatment with exagamglogene autotemcel (exa-cel) eliminates vaso-occlusive crises, according to a study published in the April 24 issue of the New ...
- Walgreens expands specialty pharmacy with unit dedicated to cell and gene therapies
Walgreens Boots Alliance (WBA) expands specialty pharmacy services with dedicated unit for gene and cell therapy. Read more here.
- Researchers publish final results of key clinical trial for gene therapy for sickle cell disease
In a landmark study, an international consortium led by researchers at Children's Hospital of Philadelphia (CHOP) published the final results of a key clinical trial of the gene therapy CASGEVY ...
- CT Up Close: Students with sickle cell disease share key takeaways from visit to NASA space center
Last month, about 20 local students with sickle cell disease traveled to NASA’s Goddard Space Center in Maryland to learn more about STEM careers and what they can ...
- CASGEVY gene therapy eliminates vaso-occlusive crises in sickle cell patients
In a landmark study, an international consortium led by researchers at (CHOP) published the final results of a key clinical trial of the gene therapy CASGEVY (exagamglogene autotemcel) for the ...
Go deeper with Google Headlines on:
Sickle cell disease
[google_news title=”” keyword=”sickle cell disease” num_posts=”5″ blurb_length=”0″ show_thumb=”left”]
Go deeper with Bing News on:
CRISPR-Cas9
- CRISPR is promising to tackle antimicrobial resistance, but bacteria can fight back
In his presentation "How to use CRISPR-Cas to combat AMR" at the ESCMID Global Congress, Assistant Prof. Ibrahim Bitar, Department of Microbiology, Faculty of Medicine and University Hospital in Plzen ...
- Buy Rating on Crispr Therapeutics AG Backed by Exa-cel’s Precision and Favorable Safety Profile
Salim Syed, an analyst from Mizuho Securities, maintained the Buy rating on Crispr Therapeutics AG (CRSP – Research Report). The ...
- This AI Just Designed a More Precise CRISPR Gene Editor for Human Cells From Scratch
Based on large language models—the tech behind the popular ChatGPT—Profluent's AI designed a new gene editor and put it to work in human cells.
- Peninsula biotech co-founded by Jennifer Doudna lands CRISPR gene-editing pact with Regeneron
The big deal between Regeneron and a Peninsula biotech co-founded by Jennifer Doudna is also a small deal. And that’s a huge deal.
- Regeneron and Mammoth strike $100M deal to pair tiny CRISPR editors with new delivery idea
Regeneron is expanding its genetic medicine efforts and will work with California startup Mammoth Biosciences on gene-editing programs reaching parts of the human body beyond the liver, the companies ...
Go deeper with Google Headlines on:
CRISPR-Cas9
[google_news title=”” keyword=”CRISPR-Cas9″ num_posts=”5″ blurb_length=”0″ show_thumb=”left”]