Transferrin for use in the treatment and/or prophylaxis of autoimmune diseases
Inventors
Farina, Claudio • Ascione, Ester • Giovacchini, Pierangelo • Nicoletti, Ferdinando
Assignees
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Publication Number
US-9138454-B2
Publication Date
2015-09-22
Expiration Date
Abstract
The present invention describes pharmaceutical compositions containing APOTf for use in preventing (or delaying the onset) and treating autoimmune diseases. Based on the experimental data obtained, the molecule has the surprising capacity to favorably modify the immune response profile both in vitro and in vivo.
Core Innovation
The invention relates to pharmaceutical compositions containing apotransferrin (APOTf) for preventing or delaying onset and for treating autoimmune diseases. The problem addressed is immune hyperactivation in autoimmune diseases, characterized by an immunological profile dominated by a T-helper 1 (Th1) profile rather than a T-helper 2 (Th2) profile associated with immune tolerance.
APOTf is described as modulating immune responses in vitro and in vivo by inducing a transition from a Th1 profile, characteristic of immune hyperactivation, to a Th2 profile, typical of immune tolerance. The rationale is expressed in terms of shifting the Th1/Th2/Tc1/Tc2 balance in autoimmune settings involving Th1-associated cytokines such as IL-2 and IFN-γ, and Th2-associated cytokines such as IL-4 and IL-5.
Therapeutic or prophylaxis regimens are provided with a preferred daily dosing range for APOTf of 1–10 mg/kg, more preferably 1–5 mg/kg, and disease-specific regimen thresholds. The document reports experimental efficacy in multiple sclerosis, rheumatoid arthritis, intestinal colitis, type 1 diabetes, and autoimmune hepatitis models, including measured reductions in clinical and histological disease parameters and improved tolerability.
Claims Coverage
The independent claims cover methods of treating autoimmune diseases by administering apotransferrin (ApoTf) to induce an immunological profile transition from a T-helper 1 (Th1) profile associated with immune hyperactivation to a T-helper 2 (Th2) profile typical of immune tolerance. The claims include four inventive features, focused on the ApoTf-mediated Th1-to-Th2 transition, the selected autoimmune indications, and prolonged administration and daily dosing constraints.
ApoTf-induced Th1-to-Th2 immunological transition for autoimmune disease treatment
Administering a therapeutically effective amount of Apo-transferrin (ApoTf) to induce a transition from the T-helper 1 immunological profile, characteristic of patients with pictures of immune hyperactivation, to the T-helper 2, typical of conditions of immune tolerance.
Selected autoimmune disease indications for ApoTf immunological profile transition
Treating an autoimmune disease selected from the group consisting of multiple sclerosis, rheumatoid arthritis, inflammatory bowel syndromes and autoimmune hepatitis by administering a therapeutically effective amount of Apo-transferrin (ApoTf) for inducing the transition from a T-helper 1 immunological profile to a T-helper 2 immunological profile.
Prolonged ApoTf administration at therapeutically effective daily dose range
Administering, over a prolonged period of at least six times a week for at least six consecutive weeks, a therapeutically effective daily amount of Apo-transferrin (ApoTf) comprised between 2.5 and 10 mg/kg for inducing a transition from the T-helper 1 immunological profile to the T-helper 2 immunological profile.
Prolonged ApoTf administration for type 1 diabetes mellitus
Treating type 1 diabetes mellitus by administering, over a prolonged period of at least six times a week for at least six consecutive weeks, a therapeutically effective daily amount of Apo-transferrin (ApoTf) comprised between 2.5 and 10 mg/kg for inducing a transition from the T-helper 1 immunological profile to the T-helper 2 immunological profile.
Across the independent claims, the core inventive concept is the administration of Apo-transferrin (ApoTf) to induce an immunological profile transition from Th1 (immune hyperactivation) to Th2 (immune tolerance). The claim coverage further specifies the autoimmune disease indications and adds constraints relating to prolonged dosing schedules and defined therapeutically effective daily dose ranges, with separate coverage for type 1 diabetes mellitus.
Stated Advantages
Improved tolerability as reported in experimental efficacy results.
Reductions in clinical and histological disease parameters as reported in experimental efficacy results.
Documented Applications
Treating multiple sclerosis using ApoTf to induce a transition from Th1 to Th2 profiles in an experimental autoimmune encephalomyelitis (EAE) model.
Treating rheumatoid arthritis in adjuvant-induced arthritis and collagen-induced arthritis experimental models using ApoTf.
Treating intestinal inflammatory diseases using an experimental colitis model (DNBS/DNB-induced colitis) with ApoTf.
Treating type 1 diabetes in NOD mice and BB rats, including accelerated and cyclophosphamide-induced settings, using ApoTf.
Treating autoimmune hepatitis using a ConA-induced hepatitis experimental model with ApoTf.
Preventing or delaying onset and treating autoimmune diseases using pharmaceutical compositions containing apotransferrin (APOTf).
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