Methods and compositions for the treatment of radiation-related disorders
This invention relates, in part, to methods and compositions that are useful for the treatment and/or prevention of various disorders, including radiation-related disorders, such as acute radiation syndrome.
1. A method of treating acute radiation syndrome (ARS) in a human patient, the method comprising administering to the human patient not more than a single dose of an effective amount of a composition comprising entolimod, wherein the effective amount is about 0.4 to about 0.6 μg/kg, and wherein the entolimod comprises the amino acid sequence of SEQ ID NO: 1.
2. The method of claim 1 , wherein the ARS is a result of a high dose of radiation of about 5 to about 30 Gy.
3. The method of claim 1 , wherein the high dose of radiation is sufficient for a classification of Unit Radiation Exposure Status of RES 3.
4. The method of claim 1 , wherein the human patient is administered entolimod within about 48 hours of being exposed to radiation.
5. The method of claim 1 , wherein the human patient is administered entolimod within one or more of the triage, emergency care, and definitive care stages of radiation exposure.
6. The method of claim 1 , wherein entolimod is administered parenterally or orally.
7. The method of claim 1 , wherein entolimod is administered by a single intramuscular injection.
8. The method of claim 1 , wherein entolimod is administered by controlled-release or sustained-release.
9. The method of claim 1 , wherein the ARS comprises one or more of gastrointestinal syndrome; hematopoietic syndrome; neurovascular syndrome; and apoptosis-mediated tissue damage.
10. The method of claim 1 , wherein the human patient presents a lymphocyte count reduction of about 50% within about 24 to about 48 hours of being exposed to radiation.
11. The method of claim 1 , wherein the human patient's lymphocyte count is less than about 1000/pL.
12. The method of claim 1 , wherein the treatment with entolimod is used as an adjuvant or neoadjuvant to one or more of blood products, colony stimulating factors, cytokines and/or growth factors, antibiotics, diluting and/or blocking agents, mobilizing or chelating agents, stem cell transplants, antioxidants or free radicals, and radioprotectants.
13. The method of claim 1 , wherein entolimod induces expression of NF-κB through toll-like receptor (TLR)-mediated activation.