Immune regulation treatment for MS found safe in 1st human study

Therapy seen to promote beneficial immune cell changes in RRMS

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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OCH, a molecule designed to have beneficial effects on immune regulation in multiple sclerosis (MS), led to increases in regulatory immune cell subsets and immunomodulatory gene activity in healthy volunteers and MS patients.

That’s according to data from a first-in-human study of the compound, which also found the immune regulation treatment to be generally safe.

An ongoing Phase 2 trial (NCT04211740) is now assessing OCH’s safety and efficacy in 30 MS patients at a single center in Japan. That trial is expected to finish later this year.

The new data come from a study titled, “First-in-human clinical trial of the NKT cell-stimulatory glycolipid OCH in multiple sclerosis,” published in Therapeutic Advances in Neurological Disorders.

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In MS, an imbalance in the number and function of certain immune T-cell subsets can be observed. This imbalance drives immune responses that promote autoimmunity and inflammation — hallmarks of MS.

In particular, a type of immune cell called invariant natural killer T-cells (iNKT) are often reduced in the blood of MS patients and also show functional changes compared with those in healthy people.

Although rare, iNKTs play a range of important roles in immune function, and have the capability of producing large amounts of both pro- and anti- inflammatory molecules that influence the function of other immune cells.

Scientists previously identified a compound called OCH that works to activate iNKTs and selectively promote an immunoregulatory role rather than a pro-inflammatory one.

Preclinical studies indicated that oral administration of OCH prevented the development of disease in a mouse MS model, and that its activity was dependent on iNKTs.

To determine if the compound would also benefit MS patients, researchers conducted a first in-human study of OCH. It was designed to investigate the compound’s safety, pharmacological properties, and immunomodulatory effects in healthy people and in people with MS.

Altogether, 28 people — 15 healthy volunteers and 13 relapsing-remitting MS (RRMS) patients — were enrolled at a study center in Japan. The volunteers were ages 20-50, while the RRMS patients ranged in age from 20 to 65. All of the RRMS patients were in remission at the time of study inclusion.

Healthy participants received a single dose of OCH (0.3, 1, 3, 10, or 30 mg), given as oral granules. MS participants were randomly assigned to receive OCH once per week for 13 weeks (0.3 mg dose) or four weeks (1 or 3 mg).

Concentrations of OCH in the bloodstream were dose-dependent, with peak amounts reached about 36 hours after a single dose in both healthy people and MS patients.

The levels it achieved were significantly higher than those seen in preclinical studies, indicating that OCH has better bioavailability in humans, according to the investigators. Bioavailability refers to the amount of a medication in circulation that is available to have a biological effect.

While the number of total iNKT cells in the blood did not change after OCH administration, a significant increase in regulatory T-cells (Tregs) was observed as soon as six hours after a single dose in some groups of healthy people and MS patients.

Tregs work to regulate the activity of other immune cells, thereby controlling excessive inflammation. Their activity is known to be impaired in MS, and boosting it has shown promise in people with the disease.

Oral OCH administration may correct the pro-inflammatory changes linked with disease activity in MS.

The researchers also noted that decreases in a set of potentially harmful T-cells — those positive for a protein called GM-CSF — were observed in some participants.

Moreover, changes in the activity of genes involved in immune modulation were observed with OCH treatment, including an increase in immune-regulating genes and a decrease in pro-inflammatory ones.

Altogether, the findings indicate that “oral OCH administration may correct the pro-inflammatory changes linked with disease activity in MS,” the researchers wrote.

No serious adverse events occurred in healthy participants, but four MS patients experienced such events. They included an altered state of consciousness together with an MS relapse, MS relapse presumed to have started before treatment initiation, depression, and fatigue with muscle weakness.

Still, these events were not definitively associated with OCH treatment, and some may have been related to an underlying MS relapse, the team noted.

Despite the small number of participants in the trial, the findings “provide encouraging information” to support further clinical testing, according to researchers.

In the ongoing Phase 2 study, participants were randomly assigned to receive OCH granules (3 mg) or a placebo once per week.

Its main goal is to assess the number of patients with new or enlarging lesions after six months of treatment. Relapse rates, disability, and other measures of disease activity also will be assessed. Top-line data may be expected in the next couple of months.

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