Regulus, BWH Looking Into miR-155 Blockers as Potential ALS Treatment

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

Share this article:

Share article via email
ALS progression | ALS News Today | TDP-43 and STMN2 protein study | image of scientist in lab

Regulus Therapeutics, in partnership with researchers at Brigham and Women’s Hospital, has initiated studies to evaluate a library of molecules designed to suppress microRNA-155 (miR-155) — a small molecule that regulates the activity of other genes — as a potential treatment for amyotrophic lateral sclerosis (ALS).

The agreement, effective since September, involves the hospital laboratories of Oleg Butovsky, PhD, and Howard L. Weiner, MD, both professors of neurology at Harvard Medical School. Weiner is also the director and founder of the Partners Multiple Sclerosis Center and co-director of the Center for Neurologic Diseases, both at Brigham and Women’s Hospital (BWH).

“ALS is a devastating, progressive neurodegenerative disease with a major unmet medical need,” Denis Drygin, PhD, Regulus’ chief scientific officer, said in a press release.

“We are excited by the initiation of this research collaboration with Drs. Butovsky and Weiner, who are leading ALS researchers at Brigham and Women’s Hospital, affiliated with Harvard Medical School,” added Drygin. “We look forward to the preliminary data, which are expected in the second half of 2022.”

Recommended Reading
An illustration for clinical trials includes charts and medicines.

FDA, Amylyx Meeting to Review AMX0035 for Possible Approval

MicroRNAs, or miRNAs, are small molecules of RNA that target a particular gene’s messenger RNA (mRNA) — the intermediate molecule derived from DNA that is used as template for protein production — to prevent the generation of that protein.

miRNAs are known to play important roles in many cellular processes, including maintaining nerve cell survival and function, and a single miRNA can regulate multiple mRNAs.

Previous research by Butovsky, Weiner, and colleagues showed that a pro-inflammatory miRNA, called miR-155, was overly produced in spinal cord microglia of a mouse model of ALS and in spinal cord samples of ALS patients, compared with their healthy counterparts.

Microglia are the immune cells of the brain and spinal cord. Overly active, pro-inflammatory microglia have been associated with ALS’ hallmark loss of motor neurons, the specialized nerve cells that control voluntary movement.

The researchers also found that blocking miR-155 delayed the onset and lessened the severity of ALS in a mouse model of the disease, while extending the animals’ lifespan. These beneficial effects were associated with a correction of microglia’s ALS-associated abnormal molecular signature, and restoration of their healthy functions.

These findings highlighted miR-155’s role in the development and progression of ALS, and they suggested that targeting this miRNA could be a potential way of treating the disease.

Under this partnership, researchers will evaluate the effects of miR-155-suppressing compounds designed by Regulus — a company focused on miRNA-targeting therapies — in lab-grown microglia and animal models of ALS.

Findings will be used to select compounds showing the best potential to advance into further preclinical studies, and subsequently to identify those with the most robust and favorable pharmacologic profiles to be tested in ALS patients.

“This collaboration with Regulus will build upon our body of research in ALS,” said Tracy Batchelor, MD, chairman of neurology at BWH. “We are pleased to work with a company that shares our mission to understand the [mechanisms] of ALS with the objective of developing novel therapies to treat this devastating disease.”