Dirucotide

Multiple sclerosis (MS) is one of the most common diseases of the central nervous system, affecting more than 2,500,000 people around the world. MS is the result of damage to myelin, a protective sheath surrounding nerve fibres of the central nervous system. When myelin is damaged, this interferes with messages between the brain and other parts of the body.

Altered peptide ligands (APLs) are analogues of peptide determinants with one or more substitutions at the amino acid positions required for contact with the T cell receptor. APLs can act as either partial agonists or antagonists of the T cell receptor in question. In the case of multiple sclerosis, the peptide is an altered version of myelin basic protein (MBP), one of the most important proteins attacked by the immune system in MS. MPB-reactive T cells produce the proinflammatory Th1 cytokines TNF-alpha, IL-2 and IFN-gamma, leading to the supposition that they facilitate myelin-destructive inflammation in the CNS. Research indicates that the introduction of an altered form of MBP into MS patients --a process called T cell vaccination-- may cause the body to react to normal MBP in a protective rather than destructive fashion, thereby stopping flare-ups of the disease (Integrity® Disease Briefing: Multiple Sclerosis) .

Dirucotide (MBP-8298) is a synthetic peptide that consists of 17 amino acids linked in a sequence identical to that of a portion of human MBP. The apparent mechanism of action of dirucotide is the induction or restoration of immunological tolerance with respect to ongoing immune attack at this molecular site. High doses of antigen delivered periodically by the intravenous route are expected to suppress immune responses to the administered substance. The potential benefit of dirucotide for any individual patient is therefore expected to be related to the extent to which his or her disease process is dominated by autoimmune attack at the site represented by this synthetic peptide.

BioMS Medical has designed an ambitious clinical trials program evaluating dirucotide in various phase II and phase III studies for the treatment of secondary progressive and relapsing-remitting forms of MS, including MAESTRO-01 (phase II/III, SPMS), MAESTRO-02 (follow-on, SPMS), MAESTRO-03 (phase III, SPMS) and MINDSET-01 (phase II, RRMS). Last month both MINDSET-01 and MAESTRO-03 underwent routine review by their respective independent data safety monitoring boards, both of which recommended that the trials continue without according to protocol. The U.S. FDA has granted fast-track designation to dirucotide for the treatment of secondary progressive multiple sclerosis.