Three people with inherited diseases successfully treated with CRISPR

By Michael Le Page

Sickle cell disease can distort red blood cells

Stocktrek Images, Inc/Alamy

Two people with beta thalassaemia and one with sickle cell disease no longer require blood transfusions, which are normally used to treat severe forms of these inherited diseases, after their bone marrow stem cells were gene-edited with CRISPR.

Result of this ongoing trial, which is the first to use CRISPR to treat inherited genetic disorders, were announced today at a virtual meeting of the European Hematology Association.

“The preliminary results… demonstrate, in essence, a functional cure for patients with beta thalassaemia and sickle cell disease,” team member Haydar Frangoul at Sarah Cannon Research Institute in Nashville, Tennessee, said in a statement.

Beta thalassaemia and sickle cell disease are conditions caused by mutations that affect haemoglobin, the protein that carries oxygen in red blood cells. Those with severe forms require regular blood transfusions.

However, a few people with the disease-causing mutations never show any symptoms, because they keep producing fetal haemoglobin in adulthood. Normally, fetal haemoglobin stops being produced soon after birth.

This discovery has inspired the development of treatments based on boosting fetal haemoglobin. In this trial, run by collaborating companies CRISPR Therapeutics and Vertex, bone marrow stem cells are removed from people and the gene that turns off fetal haemoglobin production is disabled with CRISPR.

The remaining bone marrow cells are killed by chemotherapy, then replaced by edited cells. This is done to ensure that new blood cells are produced by the edited stem cells, but the chemotherapy can have serious side effects including infertility.

The first two patients with beta thalassaemia no longer need blood transfusions since being treated 15 and five months ago. Nor does the patient with sickle cell disease, nine months after treatment.

The results are excellent, says Marina Cavazzana at the Necker-Enfants Malades Hospital in Paris, France, whose team has treated a 13-year-old boy with sickle cell disease using a different approach.

Although the three patients did experience some adverse effects due to the chemotherapy, the CRISPR gene editing appears safe. However, the patients may need to be monitored for the rest of their lives to be sure it has no adverse effects, says Cavazzana.

Altogether five people have now been treated. The trial was put on hold because of the coronavirus pandemic, but has now resumed.

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How Vitamin A can Reduce Scarring in Blood Vessels

While scarring is a natural part of any healing process, scar formation within our blood vessels can be deadly. A team of US researchers has developed a new biodegradable material with built-in vitamin A which has been shown to reduce scarring in blood vessels.

"When injury occurs, cells proliferate and migrate into the blood vessel, creating scar-like tissue. It can create blockages that impair blood flow," said lead researcher Guillermo Ameer from the Northwestern University.

The soft elastic material can be used to treat injured vessels or be used to make medical devices such as stents and prosthetic vascular grafts. Early tests have shown that the material can reduce cell migration - a major contributor to the scarring process - by 57%.

"In his new work, vitamin A is integrated into the material, harnessing the beneficial properties of vitamin A and allowing for its broader application in medical devices," the authors noted in a paper published in the ACS Biomaterials Science and Engineering.

This new advanced material brings together two major advantages. Its antioxidant component can reduce the oxidative stress that leads to chronic inflammation.

Vitamin A, which is released as the material degrades, can prevent or reduce scarring.

It can potentially also be used outside the body such as for wound-healing bandages for diabetic patients.

Because the new material releases vitamin A as it degrades, the potential for toxic build up is much lower.

Ameer's team can also control how quickly the material degrades - and thus releases the vitamin A - depending on how the material is produced in the laboratory.

The team now plans to explore the material's potential for additional applications. Vitamin A is already widely known for its anti-aging properties and topical antioxidants can be used to combat cell damage or improve wound healing.

Source: IANS

Encapsulated Human Islet Cells can Normalize Blood Sugar Read more: Encapsulated Human Islet Cells can Normalize Blood Sugar

Scientists studying a mouse model of diabetes have implanted encapsulated insulin-producing cells derived from human stem cells and maintained long-term control of blood sugar -- without administering immunosuppressant drugs.

 The results of the multi-institutional effort are published in Nature Medicine. People with type 1 diabetes have an overactive immune system that destroys the insulin-producing islet cells in the pancreas. Lacking that hormone, the body fails to convert sugars to usable energy, and glucose rises to harmful levels in the blood without daily insulin injections.

Islet cells have been successfully transplanted to treat type 1 diabetes, but those patients must take immunosuppressant drugs to keep their immune system from destroying the transplanted cells. Previous research had shown that rodent islet cells could normalize blood sugar levels in animal models without immunosuppression if the cells were encased in hydrogel capsules.

The semi-porous capsules allow insulin to escape into the blood, while preventing the host's immune system from attacking the foreign cells. Larger capsules, about 1.5 millimeters across, even seemed able to avoid the buildup of scar tissue, which can choke off the cells' supply of oxygen and nutrients. The new study, a collaboration led by scientists at the Massachusetts Institute of Technology and Boston Children's Hospital, used islet cells derived from human stem cells and capsules made of chemically-tweaked gel that are even more resistant to the build-up of scar tissue.

Dr. Jose Oberholzer, chief of transplantation surgery and director of cell and pancreas transplantation at the University of Illinois Hospital & Health Sciences System, professor of bioengineering at the University of Illinois at Chicago, and an author on the paper, tested several varieties of chemically-modified alginate hydrogel spheres -- in various sizes -- to see if any excelled at resisting scar-tissue formation.

Oberholzer and his coworkersat the University of Illinois at Chicago first tested the spheres to ensure they would allow the islet cells to function inside a host. Using a special microfluidic device developed at UIC under a grant from the National Institute of Diabetes and Digestive and Kidney Diseases, they delivered minute amounts of glucose into tiny wells containing encapsulated islet cells and measured the amount of insulin that seeped out.

They implanted spheres that showed promise into rodents and non-human primates to look for the development of scar tissue. They found (and reported in the journal Nature Biotechnology) that 1.5-millimeter spheres of triazole-thiomorphine dioxide (TMTD) alginate were best at allowing allowing insulin to escape while resisting immune response and the buildup of scar tissue. When implanted into a mouse model of diabetes, TMTD-alginate spheres containing human islet cells were able to maintain proper blood glucose control for 174 days -- decades, in terms relative to the human lifespan.

"When we stopped the experiment and took the spheres out, they were virtually free of scar tissue," Oberholzer said. "While this is a very promising step towards an eventual cure for diabetes, a lot more testing is needed to ensure that the islet cells don't de-differentiate back toward their stem-cell states or become cancerous," said Oberholzer. If the cells did become cancerous, he said, they could easily break through the spheres.

Oberholzer also cautioned that a cure for human diabetes would require scientists to develop techniques to grow large numbers of human islet cells from stem cells -- a worthy goal. "In the United States, there are 30 million cases of type 2 diabetes and about 2 million patients with type 1 diabetes who could potentially benefit from such a procedure," he said. "But we need to grow billions of islet cells."

Source: Eurekalert

Acetate supplements speed up red blood cell production, anemia research shows

Researchers seeking novel treatments for anemia found that giving acetate, the major component of household vinegar, to anemic mice stimulated the formation of new red blood cells.

 UT Southwestern Medical Center researchers seeking novel treatments for anemia found that giving acetate, the major component of household vinegar, to anemic mice stimulated the formation of new red blood cells.

Currently, the hormone erythropoietin is administered to treat anemia, but this treatment carries with it side effects such as hypertension and thrombosis (blood clotting). The new research, which was performed in mice, suggests that acetate supplements could eventually be a suitable supplement or possibly even an alternative to administration of erythropoietin.

"Using rational interventions based on the mechanistic insights gleaned from our current studies, we may be able to treat acutely or chronically anemic patients with acetate supplements and thereby reduce the need for blood transfusions or erythropoietin therapy," said Dr. Joseph Garcia, Associate Professor of Internal Medicine at UT Southwestern, staff physician-scientist at the VA North Texas Health Care System, and senior author of the study, published in Nature Medicine.

Anemia is the most common blood disorder, affecting some 3.5 million people, including children and women of child-bearing age, as well as many elderly persons. It can have a significant impact on quality of life, leading to fatigue, weakness, and decreased immune function. People who are anemic produce insufficient red blood cells, which deliver oxygen to tissues throughout the body.

UT Southwestern researchers began their studies by identifying a critical pathway that controls the production of red blood cells in conditions of stress, such as low oxygen. Using genetically modified mice, researchers observed that low oxygen, a state known as hypoxia, stimulates the production of acetate.
Acetate, in turn, activates a molecular pathway that ultimately results in the production of red blood cells, or erythropoiesis, by triggering the production of the protein that stimulates this process, called erythropoietin.
"Our study shows that acetate functions as a biochemical 'flare,' linking changes in cell metabolism that occur during hypoxia with the activation of a selective stress signaling pathway," Dr. Garcia said.

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The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.