‘Superhero’ DNA May Be Key to Treating Disease

(CN) — The DNA of 13 healthy adults who inherited mutated genes that should have caused debilitating or fatal diseases in infancy or childhood may hold the key to treating others, according to a recent study.

Debilitating diseases that begin during infancy or childhood are significant health issues that disrupt people's lives and cause significant stress for countless families.

While being born with mutated genes typically leads to such disorders, 13 people have proven to be unique exceptions — and potential sources for determining how to prevent several severe diseases in the future.

Researchers published a report Monday in the journal Nature Biotechnology which documents the results of searching databases containing genetic sequences for nearly 600,000 healthy adults. Of them, 13 individuals had mutated genes that generally lead to one of eight severe disorders that typically manifest by adolescence.

"The identification of resilient individuals may provide a first step toward uncovering protective genetic variants that could help elucidate the mechanisms of Mendelian diseases and new therapeutic strategies," the report stated.

The findings are the result of a three-year process that involved more than two dozens researchers exploring genetic data from 12 large-scale studies for mutations involving any of 874 genes that have been linked to 584 severe diseases.

Of the 589,306 genomes — full sets of DNA — reviewed, 15,597 people were found to have a genetic mutation that results in a severe Mendelian childhood condition — an inherited disorder that occurs by adolescence.

After careful examination, the researchers discarded nearly all of them after either discovering errors in data, or determining that the mutations likely did not lead to a severe childhood disease.

Thirteen people remained who had verifiable genetic mutations that should have led to one of eight childhood diseases: cystic fibrosis, familial dysautonomia, epidermolysis bullosa simplex, Pfeiffer syndrome, autoimmune polyendocrinopathy syndrome, atelosteogenesis, Smith-Lemli-Optiz syndrome and acampomelic campomelic dysplasia.

They are all healthy adults, free of the diseases that should have plagued them from childhood.

"Genetic superheroes, these are the success stories. There are a lot of these kinds of success stories around," Dr. Rong Chen, director of clinical genome informatics at Icahn Institute of Genetics and Multiscale Biology and a co-author of the study, said. The institute is part of the Icahn School of Medicine at Mount Sinai in New York.

Identifying why these individuals were able to survive despite their severe disorders could lead to significant progress toward establishing cures or treatments. But a significant amount of research will have to focus on other gene mutations, and whether they potentially influence the onset of a given disorder.

"As a first step, we want to focus on these extremely severe mutations and try to identify these people, and then figure out why they are successful," Chen said. "This will teach us how to potentially treat these kinds of diseases."

Chen credits the data and tools from Mount Sinai for the study's ability to move beyond traditional barriers for similar research. Mount Sinai has the full medical records of about 4 million people, he said.

Databases like Precision Medicine Initiative, the United Kingdom Biobank in Britain and the Million Veterans Program in the United States will store the reliable data on millions of people, enabling deeper research into why gene mutations do not always lead to their corresponding disorders.

"This is a new approach, using the big data for discovery. Previously, we've always tried to learn from failure by looking at people with diseases, and then trying to figure out a way to try to solve this problem," Chen said.

The 13 individuals in the study participated under the condition of anonymity, which will force the researchers to find new participants. They are hoping to find over 100,000 individuals for the next phase of their research.

"Because of the press release, we are being approached by foundations that have identified such resilient people," Chen said. "We need more people to move this field ahead."

Follow @SeanDuffyCNS

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