Treatment of disease using inter-alpha inhibitor proteins

Inventors

Lim, Yow-Pin • Stonestreet, Barbara

Assignees

Women and Infants Hospital of Rhode Island • Prothera Biologics Inc

Abstract

The invention relates to methods of treatment of medical conditions (e.g., diseases and injuries) in a mammal (e.g., a human), such as hypoxia/ischemia, burns, and viral infections (e.g., influenza, West Nile virus, and Dengue fever), in adults and in children (e.g., neonates) by administering a composition that includes an IAIP.

Core Innovation

The invention relates to treatment methods that administer inter-alpha inhibitor proteins (IαI) and/or pre-alpha inhibitor proteins (PαI) to a mammal patient in need thereof for disorders involving tissue ischemia and inflammation. The disclosure addresses ischemia resulting from hemorrhagic stroke and provides for reducing, inhibiting, or treating ischemia by using compositions comprising IαI and/or PαI. The treatment context includes brain ischemia, hypoxia, and neuroinflammation, including ischemia-reperfusion injury and hypoxic-ischemic encephalopathy.

A central focus is neuroprotection in brain ischemia/hypoxia, including conditions connected to cerebral palsy type 2 and white matter damage. The document also links IAIP changes to injury, including rapid decreases in brain IAIP levels after ischemic injury, and describes replenishment with systemic administration of IAIP reducing injury in fetal sheep models. The disclosure further presents IAIP as a biomarker for brain injury and describes modulation of injury pathways involving down-regulation of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-8, and IFN-α/γ.

The invention extends beyond brain ischemia/hypoxia to other conditions involving inflammation and tissue injury, including burns and viral infections. The disclosure provides rationale in relation to current approaches, referencing hypothermia for neonates and limitations of tPA for adults, and it discusses treatment concepts for IAIP/PAIP administration in combination with tPA. The document also describes IAIP/biomarker ontogeny and distribution, including expression patterns in CSF/choroid plexus and related somatic organ distribution across fetal and adult stages.

Claims Coverage

The provided claim set includes four independent claims. Across these independent claims, the core inventive coverage is administering compositions comprising inter-alpha inhibitor (IαI) and/or pre-alpha inhibitor (PαI) to treat or provide neuroprotection for ischemia/inflammation conditions, including hemorrhagic stroke and brain ischemia, and treating cancer-related ischemia and stroke with an additional TPA component in the same method.

Overall, the independent claims define methods centered on administering IαI and/or PαI compositions to address ischemia and inflammation, including hemorrhagic stroke, brain ischemia/CNS inflammation for neuroprotection, cancer-associated ischemia, and stroke in combination with TPA.

Stated Advantages

Documented Applications