Multiple sclerosis and Natalizumab.
Natalizumab (NTZ), defined as "the first of a new class of drugs known as elective adhesion molecule inhibitors" was developed at the beginning of 2003 to treat relapsing-remitting multiple sclerosis (MS) and was approved in the United States in November 2004. In February 2005, the production of NTZ was suspended by Producer Firms on account of the occurrence of two serious adverse events: two patients who had been taking NTZ manifested a progressive multifocal leukoencephalopathy; the patients showed progressive neurologic deterioration, initially believed to be a worsening of the pre-existing condition of MS. In March 2006, the Advisory Panel of the Food and Drug Administration voted unanimously in favor of the return of NTZ on the market with the majority of the panel also recommending that NTZ be considered the first choice of treatment in MS. NTZ should only be administered to patients who are not taking other medicines for MS and only in highly specialized centers. Inhibiting the adhesion of the circulating immune-competent cells to the vascular endothelium and reducing the precipitation of the circulating immune complexes (CICs) into the central nervous system, NTZ causes the level of the CICs to rise to values that inhibit the production of the antibodies (above all of the immunoglobulin Ms); because of the relative lack of antibodies, the pertussis toxins, no longer complexed, attack the nerve epithelia directly. We must conclude that 1) in remittent MS, between one attack and another (successive re-infection of bordetella pertussis) there are no CICs that can precipitate into the central nervous system, and thus the treatment with NTZ is useless and superfluous; 2) in chronic-progressive MS, the final result of the treatment with NTZ will be that of transforming MS into lateral amyotrophic sclerosis or progressive multifocal leukoencephalopathy; 3) in progressive MS, however, NTZ can be of considerable use in the first 2 months of antibiotic treatment to prevent the formation of new patches or the re-activation of previous ones. With the halt of toxin production (no bordetella pertussis strains resistant to erythrocyne exist) and continuing administration of the antibiotic on a long-term basis, there will be no further need of NTZ.
Fiore
Domenico
D
Viale Madonna delle Grazie, Piove di Sacco, Italia. domenicofiore@libero.it
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000936:Antigen-Antibody Complex / Q000097:blood; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors*; D002464:Cell Migration Inhibition; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D039441:Integrin alpha4 / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000936:Antigen-Antibody Complex; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D000069442:Natalizumab; D039441:Integrin alpha4