University of Iowa researchers developed a gene therapy that could prevent craniosynostosis, a condition where babies’ skull bones fuse too early, potentially eliminating the need for invasive skull surgery. 

The research team now faces steps like obtaining FDA approval for human trials, producing medical grade DNA, and proving safety in additional animal studies. 

According to the National Center for Biotechnology Information, approximately 1 out of every 2,000 babies is born with craniosynostosis, a condition where the sutural gaps, or soft spots on a baby’s skull that allow for brain growth, are closed prematurely. 

If untreated, the condition can cause a baby to have an abnormal head shape and potentially impair brain growth. 

In a study published on Aug. 22, UI researchers from Carver College of Medicine, College of Dentistry, College of Pharmacy, and the Interdisciplinary Graduate Program in Biomedical Engineering discovered a key gene.

Researchers used mice as their test subjects and found that a lone gene, miR-200a, caused the rodents to develop craniosynostosis when it was blocked, leading them to believe that miR-200a had a key role in preventing the condition.

From there, the team created a tiny, 95-nanometer gene delivery packet that released miR-200a, when injected, halted the development of craniosynostosis for infant mice that were genetically programmed to develop it. 

Brad Amendt, a professor of anatomy and cell biology in the Carver College of Medicine and the study’s corresponding author, has taken the study to the U.S. Food and Drug Administration, or FDA, hoping to test the gene therapy on human infants in the next one to two years.

The current lengthy surgery process is cranial vault remodeling, where surgeons use endoscopic tools, a medical instrument used to look inside the body, to cut or reshape the prematurely fused skull bones to free the brain and maneuver the head to correct deformities.

Amendt said a future in which gene therapy is compatible with babies would allow the surgical process of treating the condition to consist of a simple injection below the scalp. 

“This would be simple. It’s cost effective. For the patients, it’s noninvasive, which is the biggest thing,” he said. “It’s pretty traumatic for a baby to undergo these types of surgeries where they have to have a piece of their skull removed, opened, and sutured up.”

In order to get FDA approval, Amendt and the team have to raise funds to obtain Good Manufacturing Practice, or GMP, manufactured plasmid. 

A GMP plasmid is a safe, high quality copy of DNA that scientists can use to create even more DNA for medicine. The team needs a pure supply of DNA carrying miR-200a to create ongoing treatment for babies. 

Amendt has noticed the FDA prefers to test on larger animal models before moving on to human trials, which has proven to be tricky as craniosynostosis is nearly unheard of in large animals. The team plans to perform more trials with different types of mice to demonstrate its safety. 

But these hurdles are hardly enough to stop Amendt’s excitement.

“I’ve been doing research for a long time, and we really want to see our research get into the clinic,” he said. “We really want to help patient care. If we can improve patient health, patient care, that’s really what I want to see and am most excited about.”

CAPPSKids is a nonprofit organization supporting families of children with craniosynostosis and related craniofacial issues by connecting them with expert surgeons, resources, and support. Amy Galm, director of operations at CAPPSKids, has experience with cranial vault remodeling. 

Galm has seen some babies require blood transfusion or a visit to the intensive care unit or ICU. 

 “Unfortunately, we’ve had a few children pass away during that surgery due to things like heart failure and bleeding,” she said. “It’s very horrible.”

Besides research projects like Amendt’s, Galm said an important step in fighting craniosynostosis is outreach and education.

“I’ve had actual physicians contact me that said, ‘I went to med school and I never heard of this.’ [Craniosynostosis] is not that common,” she said. “Doctors and pediatricians often think it’s just flat head syndrome because they see that so often.”

Amendt said even if the gene therapy works on babies, early detection of the condition, especially before birth, is extremely limited.

Deborah Kacmarynski, a UI Department of Otolaryngology associate professor and codirector of the Cleft and Craniofacial Team, believes early detection and new potential options like gene therapy could leapfrog over each other, meaning one advancement leads to the other.

“The treatment options advancing basically gives motivation for diagnostic training to advance,” she said. “If you take one area of technology forward, then the other areas are going to come forward because now there’s a need and a value.”

Though the researchers now have to wait for a go-ahead from the FDA, Kacmarynski said their progress has already changed the craniofacial scene for the better.

“For those families who have other kiddos who’ve had [craniosynostosis] and are expecting a child, the idea that they could have kids who have much smaller surgical treatments available, or a single surgical treatment available, that’s really meaningful for those people,” she said.