Scientists Grow Diseased Organs to Better Understand Rare Disorder

In Clinical Development by Cameron

Researchers from Harvard University have for the first time grown functioning human heart tissue carrying a genetic rare disease from rare disease patient stem cells.

The tissue was grown using the organ-on-a-chip method using stem cells from patients with Barth syndrome (BTHS), a rare metabolic heart disease caused by the mutation of the tafazzin gene (TAZ) that only affects men.

BTHS is characterised by a low white blood cell count, weak heart muscles, and frequent bacterial infections. Currently the only treatment options available tackle the potentially life threatening symptoms and complications: serious bacterial infection, heart failure and arrhythmia.

Using microfluidic cell culture chips to simulate a cellular system, and stem cells derived from skin cells of two BTHS patients, the  researchers were able to study the development of the heart tissue in order to better understand how the TAZ mutation affects the hearts development.

The researchers were able to manipulate the TAZ gene and showed that the TAZ mutation is sufficient to cause the weak contraction of heart tissue found in Barth patients.

From their observations, researchers were able to create the first tissue-based model for treating the disease and correcting the genetic defects caused by the TAZ mutation that had been seen. The scientists had found that delivering the TAZ gene product to diseased tissue effectively corrected the contractile defect.

You don’t really understand the meaning of a single cell’s genetic mutation until you build a huge chunk of organ and see how it functions or doesn’t functionKevin Kit Parker, PhD

“The TAZ mutation makes Barth syndrome cells produce an excess amount of reactive oxygen species or ROS — a normal byproduct of cellular metabolism released by mitochondria — which had not been recognized as an important part of this disease,” said William Pu, from the Harvard Medical School. “We showed that, at least in the laboratory, if you quench the excessive ROS production, then you can restore contractile function.”

This project represents an opportunity for rare disease research to move up to another level. An ability to develop organs for observation and experimentation from just a few skin derived stem cells could greatly increase the opportunities for effective research into rare and orphan diseases without the need for patients to be constantly and deeply involved.

Find the paper in Nature here.