Alkaline phosphatase agents for treatment of radiation disorders
Inventors
Kaleko, Michael • FURLAN FREGUIA, Christian • Connelly, Sheila
Assignees
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Publication Number
US-12648987-B2
Publication Date
2026-06-09
Expiration Date
Abstract
The present invention relates to, inter alia, compositions and methods, including therapeutic alkaline phosphatases that find use in the treatment or prevention of the effects of radiation exposure and/or chemotherapy.
Core Innovation
The invention relates to therapeutic alkaline phosphatase (AP) agents for preventing or treating radiation-related disorders, including acute radiation syndrome (ARS), acute radiation enteropathy, and delayed radiation enteropathy/enteritis. In particular, the document focuses on intestinal alkaline phosphatase (IAP) and compositions that are administered to a subject to address radiation-associated gastrointestinal dysfunction and related syndromes.
The problem being addressed is radiation-induced injury that manifests as acute radiation enteropathy, including gastrointestinal syndrome, hematopoietic syndrome, neurovascular syndrome, and ionizing radiation induced apoptosis tissue damage. The document characterizes radiation-related damage as involving apoptosis-mediated tissue damage and describes the condition in terms of the affected syndromes associated with ionizing radiation exposure.
The core therapeutic concept is administering IAP comprising an amino acid sequence corresponding to SEQ ID NO: 2 or SEQ ID NO: 3 to treat or prevent acute radiation enteropathy. The treatment rationale described in the document includes modulation of gut barrier and inflammatory mediators associated with radiation exposure and radiation-related enteropathy, including reduction of inflammatory cytokines and tissue apoptosis.
Claims Coverage
The partial content includes one independent claim. The main inventive features are centered on administering IAP with specified SEQ ID amino acid sequences to treat or prevent acute radiation enteropathy, including defined syndrome components and apoptosis tissue damage triggered by ionizing radiation.
Treating or preventing acute radiation enteropathy with SEQ ID IAP
Administering to a subject in need thereof an intestinal alkaline phosphatase (IAP) wherein the IAP comprises the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3 to treat or prevent acute radiation enteropathy.
Defining acute radiation enteropathy by associated syndromes and apoptosis damage
Wherein the acute radiation enteropathy comprises one or more of gastrointestinal syndrome, hematopoietic syndrome, neurovascular syndrome, and ionizing radiation induced apoptosis tissue damage.
Using SEQ ID NO: 2 or SEQ ID NO: 3 IAP
Wherein the IAP comprises the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3.
Across the independent claim coverage in the partial content, the invention is directed to treating or preventing acute radiation enteropathy by administering IAP with amino acid sequences corresponding to SEQ ID NO: 2 or SEQ ID NO: 3, where the enteropathy includes gastrointestinal, hematopoietic, and/or neurovascular syndrome manifestations and/or ionizing-radiation-induced apoptosis tissue damage.
Stated Advantages
Prevents or treats acute radiation enteropathy in a subject in need thereof.
Reduces morbidity and mortality.
Accelerates recovery.
Reduces intestinal fibrosis.
Suppresses apoptosis-mediated tissue damage.
Reduces inflammation/injury mechanisms.
Preserves gut barrier integrity, including reduced FITC-dextran leakage.
Attenuates pro-inflammatory cytokines.
Improves tight-junction gene/protein expression and reduces histologic injury.
Supports long-term protection in delayed radiation enteropathy models.
Documented Applications
Treatment or prevention of acute radiation enteropathy in a subject in need thereof, including manifestations comprising gastrointestinal syndrome, hematopoietic syndrome, neurovascular syndrome, and ionizing radiation induced apoptosis tissue damage.
Preventing or treating acute radiation enteropathy/enteritis associated with radiation exposure in a subject, including manifestations corresponding to acute radiation syndrome (ARS) syndromes and apoptosis-mediated tissue damage.
Radiation-induced intestinal fibrosis and radiation enteropathy, including delayed radiation enteropathy models.
Radiotherapy contexts with defined administration timing across prodromal, latent, and manifest stages.
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