Multiple Sclerosis (MS) is a complex autoimmune disease affecting the brain and spinal cord. In MS, the body’s immune system mistakenly attacks myelin, the protective sheath surrounding nerve fibers, leading to communication disruptions. This damage can result in varied symptoms such as muscle weakness, vision changes, numbness, and problems with balance or coordination. While there is no cure, research explores novel treatment approaches, including utilizing parasites for therapeutic benefit.
The Hygiene Hypothesis Connection
The theoretical basis for exploring parasites as a treatment for MS stems from the “Hygiene Hypothesis.” This hypothesis suggests that reduced early-life exposure to certain microorganisms, including parasites, in highly sanitized environments may contribute to the increased prevalence of autoimmune diseases like MS in developed nations. Autoimmune conditions are more common in industrialized countries where parasitic infections are rare, contrasting with regions where these infections are endemic and autoimmune disease rates are lower. The immune system needs exposure to diverse stimuli, including microbes and parasites, to learn to differentiate between harmful invaders and the body’s own tissues. Without this early and broad exposure, the immune system may become overactive or misdirected, leading it to attack healthy self-components.
How Parasites Influence the Immune System
Parasites, particularly helminths, have evolved sophisticated ways to modulate their host’s immune system. This immunomodulation involves parasites releasing molecules that suppress the host’s immune response. MS is associated with an overactive Type 1 T helper cell (Th1) inflammatory response, which drives the attack on myelin. Helminths, however, can induce a shift towards a Type 2 T helper cell (Th2) anti-inflammatory response.
This shift involves the production of specific cytokines, signaling molecules that regulate immune cell activity. Helminths can also stimulate the generation and expansion of regulatory T-cells (Tregs). These specialized immune cells act as the “brakes” of the immune system, helping to prevent excessive immune activation and self-directed attacks. By promoting a Th2 response and increasing Treg activity, parasites can rebalance the immune system, reducing the inflammatory processes seen in MS.
Clinical Research and Therapeutic Trials
Several early-stage clinical trials have investigated “helminthic therapy” for MS. One approach uses the eggs of the pig whipworm, Trichuris suis ova (TSO), which do not mature into adult worms in humans. A small, open-label study involving ten patients with relapsing forms of MS found that TSO therapy was well-tolerated, with some gastrointestinal symptoms and eosinophilia observed. However, this study did not show a beneficial effect on new brain lesions on MRI or changes in cytokine expression.
Another research avenue involves the human hookworm, Necator americanus, administered transcutaneously as larvae. A placebo-controlled Phase 2 clinical trial, known as WiRMS, recruited 71 patients with relapsing-remitting MS or secondary progressive MS. Participants received either 25 hookworm larvae or a placebo, with monthly MRI scans and immunological blood tests. While the primary outcome of reducing new MRI lesions did not reach statistical significance for the entire group, more than half of the hookworm-treated patients had no new lesions. The study observed an increase in regulatory T-cells in the hookworm group, suggesting a biological effect on immune regulation.
Risks and Future Outlook
Introducing live parasites into the body, even in a controlled manner, carries risks. Patients in clinical trials have reported side effects such as gastrointestinal discomfort and eosinophilia, an increase in a type of white blood cell. Concerns also exist regarding the precise dosing of live organisms and unintended long-term effects. Helminthic therapy is still an experimental treatment and is not an approved or mainstream approach for MS.
Looking ahead, researchers are focused on isolating the specific anti-inflammatory molecules produced by parasites rather than using live organisms. The goal is to identify and synthesize these immunomodulatory compounds, which could then be developed into traditional pharmaceutical drugs. This approach aims to harness the therapeutic benefits of parasite-derived molecules, such as FhHDM-1 from liver fluke, without the safety concerns associated with a live parasitic infection. Such advancements could lead to safer, more precise therapies for MS and other autoimmune conditions in the future.