Despite the several therapies proposed to treat multiple sclerosis, none of them has shown to be completely effective. In every case, a strong inflammatory response, TLR-mediated, appears to contribute to this autoimmune disease.
Immunotherapy for autoimmune diseases: TLR antagonists for multiple sclerosis
The most known class of TLR antagonists is represented by different types of murine, humanized and recombinant antibodies already approved for clinical use in other diseases. Among these, the class of nanobodies (VHH-based single variable domains) with very long complementary determining regions 3 (CDR3), are capable of inhibiting efficiently different protein antigens. Due their small size (12-15 kDa), nanobodies have several additional advantages compared to conventional antibodies (150-160 kDa), such as their extreme stability towards changes in temperature and chemical environments, and resistance to extreme pH levels. Because of their reduced size, nanobodies can penetrate tissues and cells faster than the conventional antibodies, being also capable of breaking through the brain's blood barrier.
Other receptor antagonists are represented by mimetic molecules of short amino acid sequences, able to prevent the interaction of prototype proteins with their partners.
Immunotherapy for autoimmune diseases: TLR3 agonists for multiple sclerosis
Among the most promising immunotherapeutics TLR-targeting suitable to be used in multiple sclerosis therapy, TLR3 agonists play a leading role, mainly due to their capability of inducing endogenous IFN-β production. Among the investigational compounds TLR3-targeting, the mismatched double-stranded RNA molecule Ampligen® could offer promise in multiple sclerosis therapy. Ampligen® is a mismatched dsRNA with a high specificity of binding to TLR3, with a subsequent selective activation of genes for IFNs, 2-5 adenylate synthetase, and protein kinase (p68).
We can conclude that TLR modulation with small molecules acting as TLR-agonists/antagonists might represent an alternative and attractive approach in multiple sclerosis therapy. Another winning point of TLR-targeting drug is that they not show important side effects and toxicity compared with drugs commonly used in multiple sclerosis treatment. This represents an important feature in the therapy of this chronic autoimmune disease that always involves young people who will be compelled to continue the therapy for the rest of their lives.
Gambuzza ME, Soraci L, Sofo V, Marino S, Bramanti P (2016) A New Era for Immunotherapeutic Approaches in Multiple Sclerosis
Treatment. J Clin Trials 6: 253.