Pediatric sickle cell study stopped early due to positive results

Hydroxyurea shown as viable option for some children with sickle cell anemia

Source:

Medical University of South Carolina

Summary:

For some children with sickle cell disease, the drug hydroxyurea is as effective as blood transfusions to reduce blood flow speeds in the brain, a national sickle cell disease study has found. Increased blood flows are a major risk factor for stroke in these children, report investigators. 

 

 

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Pediatric/hematologist Dr. Sherron Jackson of the Medical University of South Carolina examines a patient with sickle cell disease.

Credit: Photograph by Sarah Pack, Medical University of South Carolina

Pediatric/hematologist Dr. Sherron Jackson of the Medical University of South Carolina examines a patient with sickle cell disease.

Credit: Photograph by Sarah Pack, Medical University of South Carolina

"It was a privilege to be a part of this well-designed and executed study. Russell Ware presented the results at the ASH meeting, and 18 years ago, almost to the day, I presented the STOP study results to the same meeting," said Robert J. Adams, M.D., study principal investigator, MUSC professor of neurosciences and director of the South Carolina Stroke Center of Economic Excellence. "That study showed how effective transcranial Doppler risk stratification, followed by regular red cell transfusions in those with high risk blood flow, can be in the prevention of stroke in these children. This became known as the STOP protocol and its wide adoption has been associated with a sharp drop in ischemic strokes in children with sickle cell disease. The drawback of indefinite transfusions however, was a limitation to wider use of the STOP protocol. This study shows that some children can be moved from transfusion to medication after at least a year. The combined understanding and evidence from these two studies brings us closer to achieving the National Institutes' goal of a 'stroke free generation' in sickle cell disease."

Standard treatment for children with sickle cell disease who are at high risk of stroke consists of regular blood transfusions. Children who receive regular blood transfusions are then at risk for iron overload. Chelation, or iron-reduction, therapy is needed for those receiving transfusions. The National Institutes of Health (NIH)-supported study sought to answer whether hydroxyurea would provide the same benefit as blood transfusions, given these additional treatment impacts. Hydroxyurea is the only drug approved by the Food and Drug Administration to treat sickle cell disease. The Transcranial Doppler with Transfusions Changing to Hydroxyurea (TWiTCH) study was stopped early due to positive preliminary results in November 2014.
Researchers from 26 clinical sites supported by the NIH's National Heart, Lung, and Blood Institute (NHLBI) recruited and studied 121 children ages 4 to 16 years old and divided them into two groups: one that received transfusions and one that was transitioned from transfusions to daily doses of hydroxyurea.
"No child should ever have to face the prospect of suffering through a stroke," said Gary H. Gibbons, M.D., director of the NHLBI. "Our institute is striving to achieve a stroke-free generation of children living with sickle cell disease. Studies like this are vital for moving us toward this worthwhile goal."
Study authors indicated that the findings suggest that hydroxyurea could be effective at reducing risk of stroke for other patient populations, though this was not a primary goal of the study.

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Story Source:
The above post is reprinted from materials provided by Medical University of South Carolina. Note: Materials may be edited for content and length.

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

Three Simple Suggestions for a Healthy Diet

In the article below, Ellen Fung, PhD, RD of UCSF Benioff Children’s Hospital Oakland and Farah Sultan, RD of McMaster University, share some nutritional information for people with thalassemia.

One of the most common questions we are asked as nutritionists is, “What should I be eating?” In many ways, the diet for individuals with thalassemia is no different than for anyone else: the key is balance. However, the needs for certain nutrients are much higher in thalassemia. Therefore, nutrient density is very important! This means every calorie must count. Rather than worrying about which specific foods are “good” for you or which foods are “bad,” it’s better to focus on choosing a variety of foods that are packed with vitamins, minerals, fiber and other nutrients. Making smart, balanced food choices every day can help you stay healthy.
Here are some strategies you can use:

• Eating Around the Rainbow: Healthy foods we eat come in a variety of colors: kale (green), carrots (orange), beets (red), red cabbage (purple). Fruit loops don’t count here! Each food derives its color from the rich concentration of antioxidants in its skin and flesh. The variety of colors comes from a diverse range of anthocyanins (plant pigments) and antioxidants (for example, carrots and sweet potatoes are orange because of the antioxidant, beta-carotene). By eating a variety of foods of different colors throughout the day (eating around the rainbow), you will be consuming more antioxidants, substances which are important for reducing the damage that can be caused by the free iron in your body.

• My Plate: Smaller Portions, More Vegetables and Fruit. If you are not familiar with the “My Plate” campaign from the USDA, you should take a look at it (see below and at www.choosemyplate.gov). This newest guideline for eating healthy is a simple set-up of a small plate which is divided into portions, roughly ¼ for protein, ¼ for grain/carbohydrates and ½ of the plate set aside for fruits & vegetables. If we ate all our meals this way, we would be consuming many more vitamins and minerals in our diet. Think about this the next time you sit down for lunch and dinner.

• Eat Food, not Supplements. The best way to get all of our nutrients is through our food. Most nutrients are best absorbed when they come from our food (e.g. calcium – milk, zinc – chicken) rather than in the form of supplements. Nutrients found within foods are created in such a way to avoid competition for absorption in your body whereas the form of nutrients in some supplements may result in poor absorption. Food also contains much needed fiber as well as other substances (phytochemicals, flavonoids) that are important for your health. When healthy foods are replaced by foods with poor nutrient density (e.g. empty calories) + dietary supplements, you miss out on all of the benefits of food. Not to mention the simple joys of consuming delicious, nutritious foods! However, we must be clear…Individuals with thalassemia may require certain supplements (e.g. vitamin D) in addition to their diet; but supplementation should NOT REPLACE a healthy diet.

Making healthy choices doesn’t have to be complicated — simply begin by making one change in your daily routine, such as making sure to have one colorful vegetable every day. You may just be surprised how simple it can be, and how great you can feel.
Ellen Fung, PhD RD
Associate Research Scientist
UCSF Benioff Children’s Hospital Oakland
Oakland, CA USA
Farah Sultan, RD
Master’s Degree Student, Nutritional Science
McMaster University
Toronto, ON Canada