Technology Takes on Thalassemia

Thalassemia is a family of inherited blood disorders characterized by too few healthy red blood cells with adequate hemoglobin, the protein necessary to transport oxygen. “Developing red blood cells don’t make it out of the bone marrow, and patients become horribly anemic,” says John Wood, MD, PhD, principal investigator at The Saban Research Institute of Children’s Hospital Los Angeles.

Treatment typically requires a blood transfusion every three weeks or so, but each transfusion also introduces a year’s worth of iron. “Iron is hard to come by, so the body hangs on to every molecule and recycles it,” says Wood. “Thalassemia patients are getting as much as 17 years of iron each year in transfusions. It’s too much. The liver stores it until the excess eventually spills into the endocrine glands and then into the heart.”

The heart is the breaking point. Until relatively recently, medical monitoring of patients with thalassemia involved conducting occasional, painful liver biopsies to assess levels of iron in the organ. But liver biopsies tell doctors nothing about the heart, and heart biopsies are ineffective because iron deposits found there are too heterogeneous.

“You could miss them and think everything was perfectly normal,” says Wood. “By the time a patient saw a cardiologist, it was usually too late. They were likely dead in six months, no matter what we did.”

Wood, who has a doctorate in bioengineering, believed magnetic resonance imaging (MRI) of the heart was a diagnostic solution and came to Children’s Hospital Los Angeles in 2000 intent on proving it. By 2005, he had demonstrated the efficacy of noninvasive cardiac MRIs for patients with thalassemia.

Cardiac MRIs are now the standard of care for thalassemia in the United States, where the disease is relatively rare. Patients are typically scanned annually, with treatments to remove excess iron adjusted accordingly.
“Patients get a scan of their heart, liver and pancreas, which tells us a lot about where they are on the disease spectrum,” says Wood. “We’re able to stratify risk and decide how aggressively to treat.”

The bigger challenge is fighting thalassemia where the disease is endemic: in tropical regions and among people of Mediterranean, Asian and African descent. One such place is Thailand, where an estimated 37 percent of the indigenous population carries at least one defective gene for the disease, and approximately 300,000 babies are born with the disorder each year. It is a major public health dilemma, with significant adverse economic consequences.

Read more about how a novel software tool is helping remote doctors manage this deadly disease 

Case Study Changes the Way We Look at Brown Fat

image

Brown adipose tissue (BAT) is a specialized fat that produces energy in the form of heat in order to tolerate exposure to cold.  That’s why bears have ample supplies of brown fat, and why researchers at Children’s Hospital Los Angeles and elsewhere are studying the possible connection between BAT and weight loss.

In the cover story of September’s Journal of Clinical Endocrinology and Metabolism, first author Mimi S. Kim, MD, and colleagues from the Department of Radiology and the Division of Endocrinology, show the MRI of a young patient with severe hypothyroidism in a case that may upend the way that scientists look at the role of the thyroid in creating heat. 

Read more

Engineering “Replacement Parts”

As a pediatric surgeon, Tracy Grikscheit, MD, often operates on children with an insufficient length of intestine—a condition common in premature infants. Behind the bench, Grikscheit is creating tissue-engineered small intestine (TESI) to make it possible for these patients to grow their own “replacement parts”. 

Grikscheit recently found that TESI grown from human cells contains the 4 basic cell types found in human intestine, bringing her one step closer to creating a viable treatment option for her patients.

This image shows tissue-engineered small intestine with a normal inner surface. Epithelial cells are shown in green, specialized secretory cells are in red, and blue indicates the nuclei with DNA.

It’s important to remember, especially in young children, that disease doesn’t happen in a vacuum. We always knew that history and context affected disease development and outcome, but we’re just starting to get a handle on how much.

Barbara Driscoll, PhD, investigator in the Developmental Biology and Regenerative Medicine program at The Saban Research Institute

Delving into what she calls “survivor biology,” Dr. Driscoll explores how early childhood ailments can affect future health in this ResearCHLA Magazine article.

Contact Children’s Hospital Los Angeles Research Communications
rescomm@chla.usc.edu or (323) 361-1812