Innovating to cure multiple sclerosis

Multiple sclerosis (MS) is a condition that occurs when the immune system attacks the brain and spinal cord. Over 1.8 million people worldwide have MS, according to the World Health Organization (WHO). The Philippines is among the countries with a reported 27.8% change in age-standardized rates of MS between 1990 and 2016, which is higher than the global prevalence change of 10.4%.

In MS, the body’s immune system attacks myelin, the fatty insulation that surrounds the nerves in the brain and spinal cord. This disrupts the electrical impulses that are sent through the nerves to the rest of the body and results in scars (plaques or sclerosis).

Symptoms of MS vary from person to person and depend on the location and severity of nerve fiber damage. These include vision problems, difficulty walking or keeping one’s balance, difficulty thinking clearly, numbness or weakness especially in the arms and legs, muscle stiffness, depression, problems with sexual function or urination, and feeling very tired. MS symptoms can come and go or get worse over time, especially with heat or during other infections such as urinary tract or respiratory infections.

There is currently no cure for MS. Specific MS disease-modifying therapies (DMTs) are started as early as possible to reduce the frequency and severity of relapses, slow the disease progression, manage symptoms, and improve quality of life.

For a very long time, it was not known what triggered the immune system to attack myelin, but experts suspected that genetic and environmental factors played a role. MS happens most commonly in young to middle-aged adults, more in females than males, and is more common in higher latitudes, possibly due to sun exposure and vitamin D, the WHO said.

In 2022, scientists identified the Epstein-Barr virus (EBV) as the reason why the immune system attacked myelin in people with MS. EBV is the cause of mononucleosis or glandular fever (also known as the “kissing disease”). This important discovery opened up new treatment options for MS, with clinical trials of antivirals and vaccines against EBV now under way.

Antiviral therapies could reduce EBV levels circulating in patients’ immune systems. A large international study published in the Annals of Neurology in December 2023 found that people living with HIV who were on antiviral drugs were less likely to be diagnosed with MS than the general population. However, full-scale clinical trials are needed to confirm this finding.

Two Phase I clinical trials are currently being conducted to assess the safety and the immune response induced by two EBV vaccines. The American biopharmaceutical company Moderna is conducting a clinical trial on an mRNA vaccine against EBV involving 422 healthy adults aged 18 to 30. On the other hand, the US National Institute of Allergy and Infectious Diseases (NIAID) is trialing a nanoparticle vaccine against EBV involving 82 healthy adults aged 18 to 30.

Both clinical trials are designed to train the body’s immune system to attack an EBV protein known as gp350, which enables the virus to invade immune cells.

Strong B-cell antibody responses are an important first-line defense against acute EBV infection. A previous EBV vaccine based on gp350 successfully prevented the development of glandular fever in Phase 2 clinical trials, although it was not able to prevent infection. Ongoing research has highlighted the importance of T-cell-mediated immune responses in long-term effective EBV control. B-cells and T-cells are lymphocytes, a type of white blood cell, that are key disease-fighting components of the immune system.

A study by Australian researchers published last year in Nature Communications describes a new EBV vaccine that is highly effective in laboratory models. The researchers used several strategic design elements to create a more effective EBV vaccine, according to Multiple Sclerosis Australia.

First, they used components from several EBV viral proteins to achieve wide immune coverage across various stages of EBV infection, as well as to stimulate both B- and T-cell arms of the immune system. Aside from utilizing gp350 to stimulate a strong antibody response, the team genetically engineered a protein called “EBVpoly” to activate T-cells thereby enhancing the vaccine’s global potential. They also incorporated an adjuvant, a vaccine ingredient that helps boost immune responses, with a specific focus on directing the vaccine to the lymph nodes, a critical site for immune response activation.

The EBV vaccine induced strong responses against EBV in both arms of the immune system. It was effectively targeted to the lymph nodes by the adjuvant, and immune responses in the lymph nodes were enhanced. Both arms of the immune response to the vaccine were long-lasting and detected beyond six months. Furthermore, the vaccine effectively prevented the spread of an EBV-related cancer in a laboratory model. The study represents a major advance towards an effective EBV vaccine for human use.

Continued investment and re-investment in biopharmaceutical research and development will be crucial in finding medicine and vaccine innovations that will help improve the lives of patients with MS and their families.

TEODORO B. PADILLA is the executive director of Pharmaceutical and Healthcare Association of the Philippines (PHAP). PHAP represents the biopharmaceutical medicines and vaccines industry in the country. Its members are in the forefront of research and development efforts for COVID-19 and other diseases that affect Filipinos.