New Therapeutic Avenue for Rare Pediatric Diseases

Scientists have devised a new approach for detecting and potentially heading off the effects of two rare pediatric diseases named Beckwith-Wiedemann syndrome and Silver-Russell syndrome before birth, as per the study performed in mouse models of the diseases and published in Cell Reports.

Both diseases result in growth-related symptoms in children and often lead to additional problems later in life, such as increased cancer risk from Beckwith-Wiedemann syndrome and increased metabolic disease risk from Silver-Russell syndrome.

‘Treatment before birth with an FDA-approved cancer medication that targets IGF2 signaling normalized fetal growth in the Beckwith-Wiedemann.’

"Both of these diseases have lifelong consequences," said Piroska Szab�, Ph.D., an associate professor at Van Andel Institute and the study's corresponding author. "Our findings provide a critical foundation for additional studies that we hope will translate into new, life-changing prenatal detection and treatment methods. Our goal is for children to be born healthy."

Fetuses with Beckwith-Wiedemann syndrome experience too much growth during development while fetuses with Silver-Russell experience too little growth. Likewise, about one-third of Beckwith-Wiedemann cases and two-thirds of Silver-Russell cases may arise from having either too much or too little of a protein called IGF2, which plays a critical role in fetal growth and development.

Using models of the diseases, Szab� and colleagues were able to detect and measure IGF2 in amniotic fluid and correlate variations in IGF2 levels with Beckwith-Wiedemann and Silver-Russell syndromes, opening up new opportunities for early detection.

The researchers also were able to correct IGF2 levels in a genetic experiment, essentially reversing the fetal growth problems associated with both disease models. They found that treatment before birth with an FDA-approved cancer medication that targets IGF2 signaling normalized fetal growth in the Beckwith-Wiedemann model.

More research and clinical studies are needed before it is known whether the findings hold true in humans, Szab� cautioned. She hopes to find a clinical collaborator with whom to partner for future studies.

"There's a big gap between an experiment in the lab and implementation in the clinic," Szab� said. "However, our results are a vital step toward finding ways to identify and treat these syndromes before birth."



Source: Eurekalert