ALS research into miR-155 blockers advances to animal testing stage

miR-155, a microRNA, is thought to contribute to inflammation, nerve damage

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Mice are shown standing and sitting by bottles of medicine in a laboratory.

Work into developing molecules that block microRNA-155 (miR-155) as potential treatments for amyotrophic lateral sclerosis (ALS) has advanced to the stage of testing candidate molecules in animal models of the disease.

Initiated last year, the miR-155 project is a collaboration between scientists at Regulus Therapeutics and Brigham and Women’s Hospital (BWH). The work is being led by the laboratories of Oleg Butovsky, PhD, and Howard L. Weiner, MD, both with Harvard Medical School.

“We are very excited about the latest progress in our productive partnership with Drs. Butovsky and Weiner at BWH, which brings us one step closer to translating our preclinical research into a potentially meaningful treatment for patients with ALS,” Jay Hagan, president and CEO of Regulus, said in a company press release.

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MicroRNAs, also called miRNAs, are small molecules that work to regulate the activity of other genes in the cell. Unlike the better known messenger RNA (mRNA), which carries instructions for making a protein, microRNAs are not used to make proteins. Instead, these small molecules bind to the messenger RNA of specific protein-coding genes and target them for degradation.

By regulating levels of many different microRNAs and messenger RNAs, cells are able to fine-tune how much of various proteins are produced. Abnormalities in these processes can substantially alter cellular activity, which may play a role in driving diseases like ALS.

miR-155 is a microRNA active in microglia, a major type of immune cell in the brain and spinal cord. Prior research in ALS models suggests that miR-155 is overactive in microglia of ALS patients, contributing to increased inflammation and helping to drive nerve damage in people with the disease.

In early mouse studies, reducing miR-155’s activity delayed disease onset and extended the animals’ lifespan.

Inspired by these findings, scientists at Regulus and BWH teamed up to identify molecules that can block miR-155 and that might be used as medication. In the initial part of the project, the scientists identified potential candidates in microglia cellular models.

Now, the team will evaluate the pharmacological properties of promising candidates in animal models of ALS. Preliminary results from the animal studies are expected later this year.

“We look forward to reviewing preliminary data later this year, and to further explore the impact of our anti-miR-155 inhibitors in this devastating neurologic disease,” Hagan said.