Texas A&M University researchers have been awarded a $1.8 million grant from the National Institutes of Health (NIH) to study bone regeneration throughout the lifespan to ultimately benefit individuals with Down syndrome.

The new INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project grant will help scientists understand whether bone regeneration holds the key to helping people with Down syndrome recover from fractures.

“Individuals with Down syndrome typically have poor bone health and are more prone to fractures,” said Dr. Lindsay Dawson, an assistant professor in the Department of Veterinary Physiology & Pharmacology (VTPP) and a specialist in regeneration biology at the School of Veterinary Medicine & Biomedical Sciences (VMBS), who is leading the collaboration.

“With this project, we hope to better understand the regenerative capabilities of the human body, and how we might use that information to improve bone health and fracture treatments for people with Down syndrome,” she said.

In addition to helping people with Down syndrome, findings from the new project will also aid treatment development for people with limb loss.

“Around 2.1 million people in the United States are living with limb loss, and that number is expected to double by the year 2050 because of the increase in vascular diseases like diabetes,” Dawson said. “Understanding how bone regeneration works is key to developing new treatments, including the possibility of regrowing entire limbs.”

The Dangers Of A Broken Bone

The grant is especially important given that VMBS researchers recently discovered that bone fractures in people with Down syndrome are unlikely to heal.

“Down syndrome causes a problem called non-union, where inflammation and other factors prevent correct bone repair,” said doctoral candidate Kirby Sherman, who led that research project. “Unfortunately, fractures that fail to heal can be fatal. This makes fractures a major health concern for the Down syndrome community.”

Non-union is becoming an even bigger issue for the Down syndrome population now that people with this genetic condition are living longer. The Centers for Disease Control and Prevention reports that life expectancy for people with Down syndrome has grown from 10 years in 1960 to 47 years in 2007 thanks to medical advancements, giving more time and opportunities for fractures to happen. 

“We’ve known that bone mass is lower in this population, and the increased life expectancy of this population has allowed researchers to better understand the long-term implications of their lower bone mass,” said Dr. Larry Suva, VTPP department head and Sherman’s lab supervisor. “Today, there are people with Down syndrome in their 20s and 30s who have bone mass and bone architecture consistent with someone in their 60s. They’re active members of the community and they’re playing sports. Obviously, that’s great, but if they’re at increased risk of bone fractures that won’t heal, it’s also a concern.”

Tipping The Scales

The new project was made possible by discoveries that both humans and mice can regrow the ends of their fingertips.

“We don’t normally think of body part regeneration being common in mammals,” Dawson said. “It was actually discovered in humans completely by accident in the 1970s. A child lost the tip of her finger and was mistakenly sent home from the hospital without sutures to close the wound. Eleven weeks later, the child’s fingertip had grown back completely.”

Scientists have recently discovered that mice have the same regenerative capacity, making the idea of limb regeneration in mammals more promising.

“The more we understand about bone health and regeneration, the closer we get to replicating the process in humans,” Dawson said. “Because the fingertips are the one part of the human body that we know can regenerate after amputation, studying them may help researchers learn how to induce regeneration in the rest of the limb.”

The Bone Health Dream Team

By combining bone regeneration and Down syndrome-focused research, Dawson and her collaborators are hoping to find answers that will benefit many different groups of people.

“It’s been wonderful to work with so many people who have research interests that overlap with mine,” she said. 

In addition to Dawson, Suva and Sherman, other members of the research project include Dr. Dana Gaddy, a professor in the Department of Veterinary Integrative Biosciences (VIBS); Dr. James Cai, a VIBS professor; Dr. Weston Porter, a VTPP professor; Dr. Ling Yu, a VTPP research associate professor; and Mingquan Yan, a senior research associate in Dawson’s lab.

It’s hard to say how long it will be before scientists figure out how to regrow human limbs, but researchers at the VMBS are working hard to make it happen. In the meantime, the findings from this project will go toward developing treatments, such as injectable bone regeneration agents, to help people with Down syndrome recover more easily from fractures.