January 16, 2013
Riya V. Anandwala

SLU Researchers Receive $2.5 Million NIH Grant to Improve Detection of Rare Genetic Disorders

ST. LOUIS - Researchers at Saint Louis University have received a five-year, $2.5 million National Institutes of Health grant to test a new method of screening newborns for a group of rare, but serious genetic disorders that affect approximately 200 babies born in the U.S., each year.

Adriana Montano, Ph.D. is an associate research professor
of pediatrics at Saint Louis University.

The proposed screening method, developed by SLU researchers, will use dried blood samples routinely taken at birth to test for Mucopolysaccharidoses (MPS) disorders. This group of chronic and progressive disorders occurs in approximately 1 in 25,000 births and include Morquio, Hunter and Sly Syndromes. Bone deformities, enlarged abdominal organs, hearing loss, vision impairment, valvular heart disease and mental retardation are common in people with MPS disorders. In nearly all cases, the disease is fatal with an average life expectancy of 10 to 20 years if untreated.

According to Adriana M. Montaño, Ph.D., associate research professor of pediatrics at SLU and principal investigator of the study, one challenge in treating patients with MPS disorders is diagnosing the disease before it has progressed too far. Most MPS patients are asymptomatic at birth, and do not receive a diagnosis until they are 4- to 5-years old.

"If our proposed screening method is successful, it would revolutionize the way we diagnose and treat patients with MPS disorders," said Montaño. "By the time most patients are diagnosed, the disease has already caused irreversible damage. If we were able to identify newborns with MPS disorders and begin treatment immediately, though, we could slow or even stop the progression of the disease, greatly improving their quality of life and possibly prolonging it."

Newborn screenings for a number of genetic diseases are standard practice worldwide. In this study, researchers hope to perfect a simple, cost-effective method that could be included in the standard screening series. Researchers will test the effectiveness of the new screening method, which measures three biomarkers to detect MPS disorders, and will conduct a pilot study using 200,000 newborn blood samples.

Conventional methods for detecting MPS disorders, which rely on urine samples, are not suitable for mass screening because they are laborious and expensive. The proposed method uses a two-tier strategy. Researchers will first screen all newborns for elevated levels of three biomarkers that are associated with MPS disorders. Samples that are flagged as "increased risk" in the first screening will then undergo a more rigorous test that will provide a definitive diagnosis and determine the individual's MPS subtype.

"Our proposed method has another advantage in that it can be used for monitoring the patient's response to treatments and predicting the severity of the disease," Montaño said.

About MPS Disorders

People with MPS disorders have an enzyme deficiency that prevents their bodies from properly degrading glycosaminoglycans (GAGs). GAGs are sugar chains that are important to cell function. Found throughout the body, GAGs serve a variety of functions, such as providing cushion around the knee and enabling light to pass through the cornea, which is necessary for vision. There are 11 known enzyme deficiencies, resulting in seven distinct forms of MPS.

The most common therapies used to treat patients with MPS disorders are enzyme replacement therapy, hematopoietic stem cell transplantation and gene therapy, all of which aim to restore enzyme activity. Another therapy is substrate reduction therapy, which works by reducing the amount of waste that a cell makes due to the enzyme deficiency. While there is no cure for MPS disorders, Montaño says in recent years researchers have made great strides in treating patients who have the disorders.

"The FDA has already approved therapies for some MPS types and other therapies are currently being tested in clinical trials. By the time we finish this study, hopefully we will have approved therapies for all forms of MPS," Montaño said. "We know how devastating the diagnosis of an MPS disorder is on families. But with early detection and improved therapies, we hope to offer a brighter outlook for these patients and their families."

Shunji Tomatsu, M.D., Ph.D., from the departments of biomedical research and orthopedics at Nemours/Alfred I. duPont Hospital for Children is also principal investigator on the study. Professors Tadao Orii, M.D., and Yazuyuki Suzuki, M.D., Ph.D., from Gifu University, and Seiji Yamaguchi, M.D., from Shimane University in Japan, will provide the pilot study blood samples.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, infectious disease, liver disease, aging and brain disease and heart/lung disease.

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