Engineers Crack DNA Code of Autoimmune Disorders - Drug Discovery and Development

Autoimmune diseases such as lupus and psoriasis are baffling – when the body attacks itself, there appears to be no cure or therapy that can fully stop it.

But scientists say they’ve figured out an “unexpectedly general” set of rules that determine how molecules become prone to patterns of self-destructive behavior, according to a study published this week by a UCLA team in the journal Nature Materials.

In healthy patients, viral DNA triggers an immune response by tripping a receptor called TLR9. But in patients with lupus or psoriasis, their very own “self-DNA” sets off the response.

The scientists at UCLA’s Henry Samueli School of Engineering and Applied Science and California NanoSystems Institute used several techniques to probe what was happening at the molecular level in those patients.

They found that a mix of organic and inorganic molecules were forming the patients’ DNA into a kind of liquid crystal zipper structure that bound to the TLR9 receptors – amplifying the immune response.

Typically, the two autoimmune disorders can only be treated using drugs to suppress or modulate the immune response – and by treating the effects of the immune system’s attack on the body.

The “breakthrough” research at UCLA means hope for treating autoimmune disorders at their root cause – and not just the symptoms, said the scientists.

“Our research has identified a set of rules that tell us what types of molecules or materials can set off this aspect of the immune system,” said Gerard C.L. Wong, a professor bioengineering and chemistry at the school, and the lead author. “This new knowledge will make it easier to design new therapeutic strategies to control immune responses.”

Other studies had laid the groundwork for understanding the complex cause-and-effect of the autoimmune response, including a 2012 study which showed how DNA was binding in peptides in lupus, in the journal Science Translational Medicine. A 2008 study began to show how the TLR9 receptor could be activated by the “DNA sugar backbone.”

Other independent studies, including those by the National Psoriasis Foundation, have been investigating the genetic causes of autoimmune disorders.