Two New Potential Therapies For MS Hold Promise As Treatments In Humans

By Jeff Craven

Two experimental therapies being investigated for multiple sclerosis (MS) by researchers at Thomas Jefferson University, Philadelphia, may hold promise as eventual treatments for the disease.

“The current therapies we have for MS are generalized immunosuppressants,” Abdolmohamad Rostami, MD, PhD, professor and chairman of the department of neurology at Thomas Jefferson University, said in an interview. Most of these MS treatments are “quite effective,” but carry side effects.

Dr. Rostami and colleagues recently explored the relationship between MS and a novel subset of helper T cells called ThGM cells. ThGM cells produce the chemical granulocyte-macrophage colony-stimulating factor (GM-CSF), which is present in patients with MS, can cause inflammation, and are thought to be associated with autoimmunity, although their unique contribution to MS is not well understood.

Dr. Abdolmohamad Rostami
In a study recently published Oct. 23 in the journal Science Immunology, Dr. Rostami and colleagues discovered eight different antigen-experienced CD45RA−CD4+ T cells in humans, which included ThGM cells. In GM-CSF–reporter/fate reporter mice with experimental autoimmune encephalomyelitis, they found ThGM cells have a distinct genetic profile from other T cells. The researchers also found the mouse model had ThGM cells in the periphery and central nervous system, in a similar manner to how these cells appear in humans with MS.

ThGM cells in this mouse model, however, are “different than other lineages that we already know, and this seems to be a new subpopulation of T cells,” Dr. Rostami said. Future research will focus on how to characterize these ThGM cells in humans. Discovering this connection may open the door to developing a specific immunotherapy for MS.

“If we further characterize T cells that find the marker for these ThGM cells, [we] can remove them specifically and leave the rest of the CD4 cells intact,” Dr. Rostami explained.

Potential for halting MS disease progression

Another area of research being explored by Dr. Rostami and associates is which immune-activating antigens in the myelin sheath are contributing to an autoimmune response in patients with MS. In a study published Nov. 4 in Science Translational Medicine led by Giacomo Casella, PhD, of Thomas Jefferson University, Dr. Casella, Dr. Rostami, and colleagues examined how oligodendrocyte-derived extracellular vesicles (Ol-EVs) could be used as an antigen-specific therapy for MS patients.

“The antigen-specific immunotherapy is the holy grail of treating autoimmune diseases in general,” Dr. Rostami explained. “We don’t know which antigens are attacking. If we know which antigens are attacking, then we can remove those T cells which are reacting to those antigens and we can leave the rest of the immune system intact.”

The researchers theorized that oligodendrocytes, the cells that wrap their membrane around an axon and creates a myelin sheath, may contain most or all of the myelin antigens that responsible for the autoimmune response in MS. Using a mouse model with experimental autoimmune encephalomyelitis, they harvested extracellular vesicles and discovered they contained multiple myelin antigens. When these Ol-EVs were injected back into the mouse, they had different effects depending on the timing of administration. Mice that received the Ol-EV injection before disease onset had a prophylactic effect, while administration after the disease had a therapeutic effect, even giving some mice the ability to walk again after becoming paralyzed.

Top image credit: Tom Crane/Wikimedia
Image credit: JUAN GAERTNER / Science Source

Using Ol-EVs as a therapy in humans holds promise as well, as they have been isolated in patients with MS as well. The potential treatment could be a targeted therapy that would work for most MS patients, Dr. Rostami explained. “The beauty of this technique is that if you want to use it in human MS, you can basically remove all those T cells which are reacting to the myelin sheath, because we have given all of the antigen EV to the patients. We only remove those T cells which are reactive to the myelin sheath and leave the rest of the immune system completely intact.”

Both studies were supported by grants from the National Institutes of Health. In the paper by Casella et al., three authors reported they are inventors on patent applications from Thomas Jefferson University involving a potential MS therapy with Ol-EV. In the paper by Rasouli et al., the authors reported no relevant financial disclosures.