Ketone bodies to protect tissues from damage by ionizing radiation
Inventors
Veech, Richard Lewis • Clarke, Kieran
Assignees
Tdeltas Ltd • US Department of Health and Human Services
Publication Number
US-10478415-B2
Publication Date
2019-11-19
Expiration Date
2033-11-05
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Described herein is the surprising discovery that ketone bodies protect cell and tissues from ionizing radiation. Based on this finding, methods of protecting animal tissue and cells from damage caused by radiation exposure are disclosed which include, contacting the tissue with a therapeutically effective amount of an agent including at least one ketone ester, thereby protecting the tissue from radiation damage. Ketone esters can be used to minimize, reduce and/or prevent tissue damage following intentional and accidental radiation exposure, as well as increasing the therapeutic efficacy of radiation therapies by protecting non-target tissue from incidental radiation damage.
Core Innovation
The invention discloses the surprising discovery that ketone bodies, specifically (R)-3-hydroxybutyrate and acetoacetate, and their derivatives, protect animal tissues and cells from damage caused by ionizing radiation. The methods for protecting tissue involve administering a therapeutically effective amount of ketone esters that elevate blood ketone body levels, thereby reducing or preventing radiation-induced cellular and tissue damage.
The problem addressed arises from the well-known damaging effects of ionizing radiation on biological tissues, which produce unstable ionized molecules and free radicals leading to DNA damage and apoptosis, particularly in tissues with high proliferative activity. Effective radioprotectant molecules are urgently needed to protect individuals exposed to radiation sources such as nuclear accidents, warfare, or therapeutic radiation.
The disclosure provides for methods employing ketone esters, including esters and oligomers of (R)-3-hydroxybutyrate, administered before, during, or after radiation exposure. These compounds serve as metabolic precursors that raise ketone body concentrations in the blood to protective levels (e.g., between 0.1 mM and 20 mM). The invention includes specific compounds such as the (R)-1,3-butanediol ester of (R)-3-hydroxybutyrate, and compositions formulated for various routes of administration to confer radioprotective effects, minimizing tissue damage and improving therapeutic radiation outcomes.
Claims Coverage
The patent includes one independent claim defining a method for protecting animal tissue from radiation damage by contacting the tissue with a therapeutically effective amount of an agent comprising at least one ketone ester. Three main inventive features are extracted from the claims.
Use of ketone esters for tissue protection from radiation
A method comprising administering a therapeutically effective amount of an agent including at least one ketone ester to protect animal tissue from damage caused by exposure to ionizing or non-ionizing radiation.
Timing and modes of administration for radioprotection
Contacting the tissue with the ketone ester agent before, during, or after radiation exposure, with administration occurring within specific periods relative to the exposure (up to two weeks before or after), and via multiple routes including topical, oral, intravenous, and inhalational.
Effective dosage ranges and blood ketone concentration targets
Administration of the ketone ester agent in doses sufficient to raise blood ketone body levels between 0.1 mM and 20 mM, with example dosages ranging from 5 grams to 70 grams or 70 milligrams to 5 grams per kilogram of body weight, tailored for effective radioprotection.
The claims collectively cover a method of using ketone ester compositions to protect animal tissue against radiation damage by administering these agents in therapeutically effective amounts, during specified timeframes relative to radiation exposure, using various modes of delivery, and targeting blood ketone concentrations that confer protective effects.
Stated Advantages
Ketone esters provide effective protection against radiation-induced tissue damage when administered before or after exposure.
The agents selectively protect normal tissues during therapeutic radiation without compromising cancer cell ablation.
Administration of ketone esters reduces cellular apoptosis and DNA damage caused by ionizing radiation.
The radioprotective agents are stable at room temperature and suitable for storage for use in radiological emergencies.
The methods utilize natural metabolic pathways, resulting in fewer or lesser undesirable side effects compared to other radioprotectants.
Documented Applications
Protection of personnel exposed to radioactive substances or ionizing radiation from nuclear accidents, nuclear warfare, or radioactive spills.
Minimization of tissue damage during radiation therapy and diagnostic procedures including X-rays, CT scans, mammograms, radionuclide scans, and interventional radiology.
Protection of astronauts, pilots, and flight personnel from solar and cosmic radiation exposure.
Use as radioprotectants in accidental or intentional radiation exposure scenarios to increase survival and reduce tissue damage.
Combination with chemical radioprotectants to improve outcomes when advance warning of radiation exposure is possible.
Interested in licensing this patent?