Methods for treating inflammatory disorders and traumatic brain injury using stabilized non-hematopoietic EPO short peptides
Inventors
Dowling, Peter C. • Wang, Bo • Yuan, Rui Rong • Lu, Wei
Assignees
Rutgers State University of New Jersey • US Department of Veterans Affairs
Publication Number
US-11559565-B2
Publication Date
2023-01-24
Expiration Date
2026-05-01
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Abstract
The described invention provides methods for treating an inflammatory brain disease, disorder or condition and for treating a traumatic brain injury having an inflammatory component in a subject in need thereof using isolated erythropoietin (EPO)-derived oligopeptides.
Core Innovation
The invention provides methods for treating inflammatory brain diseases, disorders or conditions, including traumatic brain injury (TBI) with an inflammatory component, using isolated erythropoietin (EPO)-derived oligopeptides. The methods involve administering a pharmaceutical composition comprising a therapeutically effective amount of at least one isolated EPO-derived oligopeptide and a pharmaceutically acceptable carrier to the subject in need thereof to treat symptoms and maintain red blood cell parameters at substantially normal levels.
The invention specifically addresses the problem that EPO, while having neuroprotective capabilities, also stimulates hematopoiesis which limits its use especially in non-anemic patients with neurological injury. The disclosed short stabilized EPO-derived peptides harness the neuroprotective and immunomodulatory effects of EPO without causing the unacceptable side effect of increased red blood cell mass. These peptides reduce tissue damage by modulating immune-inflammatory networks such as decreasing MHC class I and II expression, reducing inflammatory cytokines, and suppressing antigen-specific T cell function in the central nervous system and peripheral tissues, while maintaining hematocrit levels stable during treatment.
Claims Coverage
The patent claims cover three main inventive features related to methods of treating inflammatory or autoimmune diseases using compositions comprising isolated specific peptides.
Use of specific isolated peptides for treating inflammatory or autoimmune diseases
Administering a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of an isolated peptide consisting of the amino acid sequence of SEQ ID NO: 7, 8, 12, 34, or 35 to a subject in need, effective at ameliorating at least one symptom of diseases with an inflammatory or autoimmune component.
Treatment methods for multiple sclerosis using isolated peptides
Administering a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of an isolated peptide consisting of the amino acid sequence of SEQ ID NO: 7, 8, 12, 15, 17, 34, or 35 to a subject in need, effective at ameliorating at least one symptom of multiple sclerosis.
Treatment of neurodegenerative diseases with isolated peptides
Administering a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of an isolated peptide consisting of the amino acid sequence of SEQ ID NO: 7, 8, 12, 17, 34, or 35 to a subject in need, effective at ameliorating at least one symptom of a neurodegenerative disease.
The claims focus on methods for treating inflammatory or autoimmune diseases, multiple sclerosis, and neurodegenerative diseases by administering pharmaceutical compositions containing isolated specific peptides with defined amino acid sequences, highlighting their effectiveness in ameliorating disease symptoms.
Stated Advantages
The short EPO-derived peptides provide neuroprotection without stimulating erythropoiesis, thereby avoiding increases in hematocrit and associated side effects.
They reduce neurological deficits and inflammation, including reduction of mononuclear cell brain infiltration, axonal damage, and neuronal and glial cell death.
They maintain red blood cell indices at stable, substantially normal levels during treatment.
The peptides are effective when administered within a therapeutic window extending up to approximately 9 hours post-injury, and can be given via multiple administration routes including oral and parenteral.
Documented Applications
Treatment of inflammatory brain diseases, including multiple sclerosis, demyelinating diseases, and chronic neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's disease, amyotrophic lateral sclerosis, and age-related macular degeneration.
Treatment of traumatic brain injury with inflammatory components, including symptoms such as hypotension, hypoxemia, brain swelling, headaches, cognitive dysfunctions, seizures, coma, paralysis, and progressive neurological decline.
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