Brain–in–a–dish approach also showed two existing HIV drugs may be effective in rescuing mutated cells.
?An international team of scientists, led by University of California San Diego School of Medicine researchers, has created a human stem cell–based model of a rare, but devastating, inherited neurological autoimmune condition called Aicardi–Goutieres Syndrome (AGS). In doing so, the team was able to identify unusual and surprising underlying genetic mechanisms that drive AGS and test strategies to inhibit the condition using existing drugs.

Two repurposed FDA–approved drugs showed measurable effect, rescuing cells from the effects of AGS. The findings point to the promise of future clinical trials and to the utility of creating novel stem cell–based models of human diseases when no other models are available.

The findings were published in the August 10 online issue of the journal Cell Stem Cell.

“Our approach can now be used to investigate other neurological conditions, like autism and schizophrenia and overlapping autoimmune disorders that dysfunction in similar ways,” said Alysson Muotri, PhD, professor in the UC San Diego School of Medicine departments of Pediatrics and Cellular and Molecular Medicine, director of the UC San Diego Stem Cell Program and a member of the Sanford Consortium for Regenerative Medicine.

The researchers observed that AGS pathogenesis was similar to a retroviral infection and wondered whether existing HIV antiretroviral drugs might be effective in interfering in L1 replication. Two drugs were tested in the cell models: stavudine and lamivudine. Both drugs resulted in reduced L1 and cell toxicity. Cell model growth returned in all cell types and in the complex, differentiated colonies of nerve cells that comprise organoids.