Prader-Willi Syndrome

UConn Hosts Prader-Willi Stem Cell Biobank

Stem cells provided through a new biobank hosted at UConn will allow researchers around the world to better understand Prader-Willi syndrome and look for potential therapies for the rare genetic disease.

Stem cells provided through a new biobank hosted at UConn will allow researchers around the world to better understand Prader-Willi syndrome and look for potential therapies for the rare genetic disease.


A new collaboration between UConn Health and the Foundation for Prader-Willi Research will create a centralized, high-quality biobank of stem cells to help researchers better understand Prader-Willi syndrome, a rare genetic disease that may hold insights into obesity, developmental delays, autism spectrum disorders, and many other conditions.

The foundation (FPWR) and the UConn–Wesleyan University Stem Cell Core will jointly support the biobank of induced-pluripotent stem cells for Prader-Willi syndrome. These special stem cells are made from adult cells, and they have the potential to grow into any bodily tissue, including skin, stomach, brain, blood, and more. The biobank will be able to supply induced-pluripotent stem cells for Prader-Willi syndrome to researchers throughout the world.

Prader-Willi syndrome occurs in approximately 1 in 15,000 to 30,000 births. It’s caused when certain genes that are normally found on chromosome 15 are missing or not working. In most individuals with Prader-Willi syndrome, certain genes on chromosome 15 that should be specifically expressed from the father’s chromosome are missing. Geneticists don’t understand why, but the mother’s version of these genes is always turned off.

It’s these genes, and how their absence affects the rest of the genome’s and cells’ functions, that researchers will be able to investigate thanks to the biobank. Researchers will be able to use the induced-pluripotent stem cells to look for potential therapies for Prader-Willi syndrome. They may also be able to use the cells to explore the genetic and biomolecular basis of some of the syndrome’s symptoms, such as sleep disorders, developmental delays, and disordered eating.

UConn will host the centralized repository in the Stem Cell Core on the UConn Health medical school campus. Each Prader-Willi syndrome induced-pluripotent stem cell sample provided through the biobank will have undergone a select set of validation assays. The biobank will help facilitate research on cellular phenotypic abnormalities in Prader-Willi syndrome and ensure that precious research dollars are not spent re-creating stem cell resources that may already exist.

“The objective of FPWR’s translational research program is to reduce the amount of time and resources needed to move therapeutic studies forward,” says Nathalie Kayadjanian, director of translational research at FPWR. “Stem cells stored at the UConn Core will provide Prader-Willi syndrome researchers and pharmaceutical companies pursuing Prader-Willi syndrome therapeutics high-quality cellular resources to perform robust experiments in a timely manner.”

Currently the Prader-Willi syndrome biobank has two cell lines, one with a deletion of certain genes on the father’s copy of chromosome 15, the other with two copies of chromosome 15 from the mother and none from the father. Both cell lines were contributed by Stormy Chamberlain, Ph.D., and Marc Lalande, Ph.D., UConn Health researchers who study Prader-Willi syndrome and its sibling genetic disorder Angelman’s syndrome. More cell lines will be banked at the facility in the coming years.

Lab Discovery Could Lead to Prader-Willi Treatment

DNA strand


Stem cell researchers at UConn Health have reversed Prader-Willi syndrome in brain cells growing in the lab, findings they recently published in Human Molecular Genetics.

The discovery provides clues that could lead to a treatment for Prader-Willi, a genetic disorder that occurs in about one out of every 15,000 births, and is the most common genetic cause of life-threatening childhood obesity.

Unlike many genetic syndromes that are caused by a mutation in a gene, people with Prader-Willi often have the right gene available — it’s simply that it’s been silenced.

The gene is silenced because it is on the part of their chromosome they inherited from their mother, and for mysterious reasons our cells use the father’s copy of this gene. But if the father’s copy is missing, the cells can’t express that gene at all.

UConn Health’s Maeva Langouet, a post-doctoral fellow; Marc Lalande, professor emeritus of genetics and genome sciences; and their colleagues wondered if it was possible to reverse the silencing of the mother’s copy.

Unlike many genetic syndromes that are caused by a mutation in a gene, people with Prader-Willi often have the right gene available — it’s simply that it’s been silenced.

The researchers noticed that a certain protein, called ZNF274, was involved in the process. It silences many other genes as well, but in those cases it usually acts with another protein. On the Prader-Willi region of our DNA, the protein seems to act alone, they said.

So Langouet and Lalande took stem cells donated by Prader-Willi patients and carefully deleted ZNF274. They then encouraged the stem cells to grow into neurons, a type of brain cell. And the cells seemed normal. They grew and developed, as expected.

Critically, the new cells also expressed the maternal copy of the Prader-Willi region.

“We still need to figure out if knocking out ZNF274 is doing anything else” that might be undesirable, says Langouet.

And many other questions still need to be answered: Does this work directly in human brain cells? Will it only work in embryos, or can it help the brain develop normally even after birth?

Currently, there is no cure for Prader-Willi syndrome, and most research has been targeted towards treating specific symptoms. For many individuals affected by the disorder, the elimination of some of the most difficult aspects of the syndrome, such as the insatiable appetite and obesity, would represent a significant improvement in quality of life and the ability to live independently.

But in the future, this new line of research may offer a therapeutic approach for kids with Prader-Willi, Langouet says.

The research was funded by the Foundation for Prader-Willi Research, the Cascade Fellowship, and the CT Regenerative Medicine Fund.