Cellular response linked with Down syndrome chromosome found to impair heart development in infants


PTI, Jun 22, 2023, 2:06 PM IST

ANI photo

Scientists have observed trisomy 21, the extra copy of chromosome 21 known to cause the genetic condition Down syndrome, to impair heart formation during embryonic development, a malfunction found to cause a hyperactive cellular response when attacked by viruses.

Using stem cells obtained from research participants with Down syndrome and a mouse model of the syndrome, the scientists at the University of Colorado Anschutz Medical Campus, US, modelled cardiogenesis, or heart formation, in the lab.

The scientists demonstrated that blocking the antiviral cellular response, or the interferon response, improved cardiogenesis.

”We were surprised to see strong activity of the interferon response during differentiation of pluripotent stem cells into heart muscle cells with trisomy 21. We now appreciate that an abnormally high interferon response could be detrimental to early heart development,” explained Kunhua Song, associate professor of medicine and lead researcher.

Further, they found, interferon hyperactivity impaired cardiogenesis by inhibiting a series of key molecular events required for heart development, such as the Wnt signalling pathway.

According to Congwu Li, lead author of the paper published in the journal iScience, ”Too much interferon activity leads to too little Wnt signalling, which in turn impairs heart muscle cell function. Discovering this cascade of events illuminates potential strategies to ameliorate improper heart formation in Down syndrome by toning down interferon signalling and/or bumping up Wnt signalling.” Testing this therapeutic strategy in a mouse model of Down syndrome, the investigators treated pregnant female mice with JAK inhibitors, known to reduce interferon response. They then monitored the effects on heart development in the embryos carrying a genetic alteration equivalent to trisomy 21.

The researchers noticed a remarkable improvement in cardiogenesis in mice.

”These are very important results, because they suggest a potential pharmacological strategy for pre-natal treatment of one of the most harmful impacts of trisomy 21.

”Babies born with Down syndrome and congenital heart defects face a number of challenges, from the need of heart surgery soon after birth to long lasting impacts on their physiology later in life.

”However, a lot of additional research will be needed to define the safety and efficacy of using JAK inhibitors during pregnancy,” said Joaquin Espinosa, executive director of the Linda Crnic Institute for Down syndrome at the University of Colorado and co-author of the paper.

Espinosa and his team are currently leading clinical trials studying the benefits of JAK inhibitors in older children and adults with Down syndrome.

These findings expand, they said, on a growing body of evidence demonstrating the harmful effects of interferon hyperactivity in Down syndrome, even during early stages of embryonic development.

The results also support the idea, they said, that many of the hallmarks of Down syndrome are driven by lifelong dysregulation of the immune system and that restoring immune balance could provide therapeutic benefits.

Udayavani is now on Telegram. Click here to join our channel and stay updated with the latest news.

Top News

Actress Kasthuri released from jail, says ‘I thank those who made me raging storm’

Kidnapped for ransom in 1998, 26/11 survivor Gautam Adani faces biggest trial

100 engineering colleges in Karnataka to be ‘adopted’ by corporates by next year: IT Minister Kharge

Siddaramaiah defends BPL ration card cancellation, says only ineligible beneficiaries affected

China announces new policy measures to protect its exports from Trump’s new tariff threat

Renovated Medical Oncology OPD and Chemotherapy Day Care Centre inaugurated at Kasturba Hospital, Manipal

Karnataka Health Minister justifies revision of user fees in state-run hospitals

Related Articles More

World COPD Day: Know your lung function

As Delhi chokes with dangerous pollution levels, doctors warn of health risks for all

World Diabetes Day 2024: Kasturba Hospital Manipal Hosts Zumba Session at Malpe Beach to Raise Diabetes Awareness

World Diabetes Day: An overview of types of diabetes

World Diabetes Day: One-fourth of people living with diabetes in 2022 are in India, Lancet study estimates

MUST WATCH

Christmas Cake Fruit Mixing

DK Shivakumar

Rose Cultivation

Geethotsava

Naxal Operation


Latest Additions

Siddaramaiah says confident of winning all three bypolls in Karnataka

Hop on! IT Minister Priyank Kharge checks out Uber Shuttle at Bengaluru Tech Summit

Actress Kasthuri released from jail, says ‘I thank those who made me raging storm’

Kidnapped for ransom in 1998, 26/11 survivor Gautam Adani faces biggest trial

AIMPLB to hold its annual general sessions in Bengaluru from November 23

Thanks for visiting Udayavani

You seem to have an Ad Blocker on.
To continue reading, please turn it off or whitelist Udayavani.