Compositions and methods for treating Crohn's disease and related conditions and infections

Inventors

Agrawal, Gaurav

Assignees

Agrawal Guarav • Centre for Digestive Diseases Pty Ltd

Abstract

In alternative embodiments, the invention provides a “triple combination” therapy for treating, ameliorating and preventing Crohn's Disease (or Crohn syndrome, terminal or distal ileitis or regional enteritis) or related disorders and conditions in mammals, such as paratuberculosis in mammals, or Johne's disease, including genetically-predisposed and chronic disorders, where the microbial or bacterial flora of the bowel is at least one causative or symptom-producing factor; and compositions for practicing same. In alternative embodiments, methods and compositions of the invention comprise or comprise use of therapies, medications, formulations and pharmaceuticals comprising active agents that can suppress or eradicate the microbiota super-infection that causes Crohn's Disease or paratuberculosis infection in mammals. In alternative embodiments, the methods and uses of the invention for treating, ameliorating and preventing Crohn's Disease and complications of Crohn's Disease, or related disorders and conditions in mammals, such as paratuberculosis in mammals, or Johne's disease, comprises administration to an individual (human or mammal) in need thereof: (1) an anti-TNFα composition, or a composition capable of down-modulating TNFα activity; (2) a Hyperbaric Oxygen Treatment, or HBOT; and (3) an anti-Mycobacterium avium sub species paratuberculosis (MAP) (an anti-MAP) agent, composition or therapy.

Core Innovation

The invention provides a therapeutic combination for treating or ameliorating Crohn’s Disease, or a complication of Crohn’s Disease. The combination comprises an anti-TNFα agent capable of down-modulating or down-regulating TNFα activity, an anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, or drug, and hyperbaric oxygen. The therapeutic combination is applicable to Crohn’s Disease and related complications.

The anti-TNFα component includes an agent capable of down-modulating or down-regulating TNFα activity, with infliximab and adalimumab identified as example anti-TNFα drugs and other listed anti-TNFα agents. The anti-MAP component includes rifabutin and/or clarithromycin, including combinations of rifabutin and clarithromycin. The disclosures describe scheduling options in relation to hyperbaric oxygen treatment and anti-MAP therapy.

The invention also relates to fistulising Crohn’s disease and Crohn’s disease-related fistulae and complications, including recto-vaginal and perianal fistulae. The disclosures provide a biological rationale connecting TNFα to autophagy/apoptosis in MAP-containing cells and discuss use with imaging and clinical outcome measures. The disclosed examples report near-100% healing of perianal and recto-vaginal fistulae using concurrent infliximab with continuous anti-MAP therapy and hyperbaric oxygen in previously treatment-refractory patients.

Claims Coverage

The independent claim covers a therapeutic combination with three required components: an anti-TNFα down-modulating/down-regulating agent, an anti-MAP agent, and hyperbaric oxygen. Dependent claims refine the anti-TNFα examples, define the anti-MAP agents as rifabutin and/or clarithromycin, add a rifabutin plus clarithromycin pairing, and narrow the indication to fistulising Crohn’s disease and Crohn’s disease-related fistulae and complications.

Overall, the claim set is directed to a three-component therapeutic combination requiring anti-TNFα down-modulation plus anti-MAP therapy together with hyperbaric oxygen, with dependent claim refinements specifying rifabutin/clarithromycin (including rifabutin plus clarithromycin) and narrowing to fistulising Crohn’s disease and related fistulae and complications.

Stated Advantages

Documented Applications