Duke researchers have discovered a new way to model progeria syndrome—a rare genetic disease that accelerates aging in children—which could help lead the way for future treatments.
Leigh Atchison, a doctoral candidate in biomedical engineering and contributor to the study, explained that progeria affects fewer than 200 children worldwide. This apparent rarity makes it difficult to test and develop possible therapies, she said.
“Because kids with progeria die on average between the ages of 10 and 15, passing on the genetic defect is unlikely," Atchison said. "It’s been really hard to get patient samples to test treatments."
The syndrome is caused by an accumulation of the mutant protein progerin outside of the cell nucleus, which creates an abnormal nucleus shape and prevents normal cell division.
Using a grant from the National Institutes of Health, Atchison and her team developed human blood vessels in their lab that could mimic several conditions associated with progeria, paving the way for more realistic drug testing.
In particular, the team's engineered blood vessels mimicked the symptoms of individuals affected by progeria by recreating the smooth, deteriorated muscle cells which are responsible for the forms of cardiovascular disease that are dangerous to progeria patients.
The team found that smooth muscle cells derived from stem cells isolated from patients with progeria—along with healthy cells from their parents—could be used to create functional tissue-engineered blood vessels that mimic the characteristics of progeria cells, explained George Truskey, R. Eugene and Susie E. Goodson professor of biomedical engineering, in an email.
Truskey said he was surprised that the progeria patients' cells they used ultimately gave rise to the engineered blood vessels, since cells from progeria patients have been described to divide inefficiently and are prone to early death.
Prior to the development of new technology for modeling progeria cells, Atchison said there were three primary ways to study the disease and its treatment—mouse models, two-dimensional cell cultures taken from autopsy samples and the relatively small number of cells sampled directly from patients.
Since very few patients have historically enrolled in trials that test treatments—usually about three patients—demonstrating the efficacy of any regiment has always been difficult. The group's new model could help increase the efficiency of new endeavors, Atchison noted
“Our model is supposed to supplement those [models] currently used in clinical studies," she said. "In addition to there not being many patients to take cell samples from, both mouse models and two-dimensional cell cultures have not been able to show the exact phenotype that occurs in humans."
The researchers are now gearing up to use their blood vessel model to identify which of the existing 16 approaches for progeria treatment are the most promising and could be best improved.
So far, the greatest progeria drug success has been increasing lifespans by an average of three months, leaving researchers and patients eager for more advances.
The team piloted the drug Everolimus, which is currently under clinical trials for progeria treatment, using the blood vessels. Atchison explained that while the drug was able to improve vascular function, it ultimately did not remedy all of the Progeria symptoms.
Still, since the underlying technology of their engineered vessels is adaptable to other models, Atchison said she remains hopeful of advancing their research.
“Since the cells used in this technology are stem cells, they can be used to model any genetic disease, no matter how rare," she said. "We are working towards validating the model as an effective screening method for progeria treatments and will be trying to model other diseases."
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