Treatment Approaches for Multiple Sclerosis

Overview of Multiple Sclerosis

Most treatments for multiple sclerosis (MS) focus on managing symptoms and slowing disease progression. Canada has one of the highest rates of MS globally. This autoimmune condition affects the protective covering of nerve cells, hindering or blocking the transmission of neural impulses. Symptoms can include fatigue, weakness, sensory impairment, and cognitive as well as emotional disturbances.

Stages of Multiple Sclerosis

In the early stages of MS, patients typically experience relapses marked by symptom flare-ups followed by periods of remission. Over time, these attacks may become increasingly disabling, leading to the secondary progressive stage of MS, where relapses cease, but the disease continues to worsen.

Research on Natalizumab

Effectiveness in Treating MS

Natalizumab has demonstrated effectiveness in reducing inflammation during relapses of MS. It targets both the peripheral immune response and the intrathecal immune response within the spinal canal. By inhibiting the movement of white blood cells across the blood-brain barrier, natalizumab disrupts the recruitment of inflammatory cells into the central nervous system, thereby reducing inflammation.

Phase-3 Clinical Trial

To further explore this treatment, researchers initiated a phase-3 clinical trial to determine whether natalizumab can safely treat and slow disease progression in non-relapsing secondary progressive MS. The findings were published in The Lancet Neurology.

The trial enrolled 889 patients aged 18-58 who had been diagnosed with non-relapsing secondary progressive MS for at least two years. In the initial phase, participants received either intravenous natalizumab or a placebo every four weeks for two years. Subsequently, all patients were transitioned to natalizumab treatment.

Assessment of Disability Progression

The researchers measured disability progression using the Expanded Disability Status Scale (EDSS), the Timed 25-Foot Walk (T25FW), and the 9-Hole Peg Test (9HPT), which evaluate overall function, lower extremity function, and upper extremity function, respectively.

While the first phase of the trial did not show significant effects on the EDSS or T25FW scores, a notable reduction in 9HPT progression was observed when compared to the placebo. This effect persisted in the second phase. The rate of adverse events was similar between the placebo and treatment groups in the initial phase; however, those continuing on natalizumab experienced a higher rate of adverse events in the second phase.

Conclusion and Future Directions

Implications of Findings

The results indicate that natalizumab may assist in preserving upper-limb function, although it might not significantly impact overall disease progression or lower limb function. The study authors emphasize the importance of upper limb function preservation for maintaining independence and quality of life in MS patients.

Researchers advocate for long-term trials to evaluate any additional measurable benefits of natalizumab treatment in individuals with non-relapsing MS.

References

(1) Kapoor R et al. Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension. Lancet Neurol. 2018 May;17(5):405-415. doi: 10.1016/S1474-4422(18)30069-3. Epub 2018 Mar 12.
(2) Multiple Sclerosis Society of Canada. What is MS? https://mssociety.ca/about-ms/what-is-ms
(3) Multiple Sclerosis Society UK. Secondary progressive MS. 2017 – A year of breakthroughs in MS research https://www.mssociety.org.uk/about-ms/types-of-ms/secondary-progressive-ms.