Treatment with a potential remyelinating agent called liothyronine was safe and well-tolerated by people with multiple sclerosis (MS) in a Phase 1b trial. Preliminary results also suggested benefits in cognition, motor function, and fatigue.

The study, “A Phase 1b, open-label study to evaluate the safety and tolerability of the putative remyelinating agent, liothyronine, in individuals with multiple sclerosis,” was presented today at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) , by Scott D. Newsome, professor of neurology at John Hopkins University School of Medicine.

ECTRIMS 2019 is being held in Stockholm, Sweden, from Sept. 11 to 13.

According to Newsome, thyroid hormones are critical for the development of the nervous system. These hormones may promote remyelination — the formation of new myelin sheaths, the protective coating around neurons — in the central nervous system (brain and spinal cord) by boosting the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes. Those are the cell types that form myelin.

Tri-iodothyronine (T3) is believed to play a central role in the most important actions of the thyroid hormones. Therefore, researchers believe that liothyronine — a synthetic form of T3 — may induce repair and limit neurodegeneration in people with MS.

Aiming to assess the safety and tolerability of increasing oral doses of liothyronine, a team from John Hopkins University School of Medicine and Rush University Medical Center conducted a single-center study (NCT02506751) in 20 adults — ages 18 to 58 — with relapsing and progressive MS. The study lasted 24 weeks.

Liothyronine was given at 10 micrograms (mcg) daily during the first six weeks. It then was increased to 20 mcg in weeks 6-12, to 50 mcg in weeks 12-18, and to 1 mcg/kg of body weight/day (not exceeding 75 mcg) in weeks 18-24.

The eligibility criteria included an Expanded Disability Status Scale (EDSS) score — a method of quantifying disability and monitoring changes in the level of disability over time — between 3.0 and 7.5, and having normal thyroid function.

The trial’s secondary outcomes included changes in depression, health-related quality of life, and processing speed, which is frequently impaired in MS patients and refers to the time taken to understand and react to information. In a physical measure, the secondary outcomes also included changes in the timed 25-foot walk (T25FW) — a test requiring patients to walk 25 feet as quickly as possible, but safely.

Biospecimens — which may include tissue, blood, and urine — were collected to assess exploratory biomarkers of treatment response. Age, sex, disease subtype/duration, and body mass index all were accounted for in the analysis of liothyronine’s effects.

Participants had a mean age of 46.4 years, and included nine men and 11 women. A majority of the patients (12) had relapsing-remitting MS (RRMS), while eight had progressive MS. Their baseline mean EDSS score was 4.4. A score of 4.5 means the patient has some limitations or disability, and may require minimal assistance to walk.

Results showed that treatment with liothyronine was well-tolerated, with no serious treatment-related adverse events, nor evidence of disease activation or clinical worsening.

“The most common adverse events included gastrointestinal distress and abnormal thyroid function tests, although no clinical thyrotoxicosis [excess thyroid hormone in blood] occurred or was unmasked over time,” Newsome said.

In early analyses, T25FW scores improved in the eight patients with progressive disease, while those with RRMS showed a trend toward improved processing speed and less fatigue. However, “we have to be cautious” with these results, Newsome said, as the number of participants analyzed is small.

Overall, “liothyronine was tolerated well, without treatment-related severe/serious adverse events or evidence of MS disease activation/clinical deterioration,” Newsome concluded.

The researcher emphasized that a larger clinical trial will help determine if liothyronine boosts the formation of oligodendrocytes, promotes remyelination, limits nerve fiber degeneration, and improves function in MS patients.