Stoke’s RNA-focused Therapy Generates Protein Lacking in Dravet Syndrome, Mouse Study Shows

José Lopes, PhD avatar

by José Lopes, PhD |

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An RNA splicing technique that Stoke Therapeutics is developing led to the production of a protein that’s lacking in Dravet syndrome, a study in mice showed.

Stoke discussed the approach at the Oligonucleotide & Peptide Therapeutics Conference in Boston, March 26-28. Dr. Charles R. Allerson, Stoke’s vice president of chemistry, delivered the presentation, which was titled “Targeted Augmentation of Nuclear Gene Output.”

The company is developing compounds called antisense oligonucleotides that are intended to increase genes’ production of proteins that are faulty or whose levels are insufficient in a number of genetic diseases.

These compounds target a process known as RNA splicing. It involves removing small bits of RNA called introns from the pre-messenger RNA that a gene produces as a first step toward  generating the set of instructions that messenger RNA needs to produce proteins.

One of the disorders that Stoke hopes to treat with this approach is Dravet syndrome. In about 85 percent of cases, this form of severe epilepsy is caused by a mutation of the SCN1A gene.

The normal gene generates part of a sodium channel called Nav1.1 that regulates sodium’s entry into cells. The right amount of sodium is crucial to cell communication in the brain.

Stoke scientists used antisense oligonucleotides to increase production of Scn1a messenger RNA and the Nav1.1 protein it helps generate without affecting non-sodium ion channels. This approach could lead to the first disease-modifying therapy for Dravet syndrome, Stoke researchers said.

“We’re excited to share our early data as we work to develop a pipeline of innovative” antisense oligonucleotides, Allerson said in a press release. “Many human genetic diseases are due to loss or reduction of function of a single gene, yet there are no drugs on the market to address the underlying genetic causes of most of these conditions.”

Stokes uses what it calls a bioinformatics engine to look for genes whose mutations could result in faulty or insufficient production of proteins and thus the development of a disease.

In addition to disorders like epilepsy that affect the central nervous system, Stoke wants to develop treatments for eye and liver conditions.