Researchers at Fred Hutchinson Cancer Research Center ( FHCRC ) in Seattle have, for the first time, induced a state of reversible metabolic hibernation in a mouse model.

The induced metabolic hibernation in a mammal could lead to new ways to treat cancer and prevent injury and death from insufficient blood supply to organs and tissues.

During a hibernation-like state, cellular activity slows to a near standstill, which reduces dramatically an organism's need for oxygen.

Clinical applications of induced metabolic hibernation could include treating severe blood-loss injury, hypothermia, malignant fever, cardiac arrest and stroke.

The potential medical benefits also include improving cancer treatment by allowing patients to tolerate higher radiation doses without damaging healthy tissue.
Cancer cells aren't dependent on oxygen to grow.
As a result, they are more resistant to radiation than surrounding healthy cells, which need oxygen to live.
Temporarily eliminating oxygen dependence in healthy cells could make them a less-vulnerable target for radiation and chemotherapy and thus spare normal tissue during high-dose cancer therapy.

Using oxygen deprivation to depress metabolic activity also might extend the amount of time that organs and tissues could be preserved outside the body prior to transplantation.

Yet another potential application of oxygen deprivation would include accelerating wound healing in patients, such as diabetics, whose ability to do so is compromised. This could reduce the number of amputations caused by irreparable tissue damage from wounds that won't heal.

Mark Roth, a member of Fred Hutchinson’s Basic Sciences Division, and colleagues induced a state of clinical torpor in mice for up to six hours before restoring their normal metabolic function and activity.

They achieved this by placing the mice in a chamber filled with normal room air laced with 80 parts per million of hydrogen sulfide, a chemical normally produced in humans and animals that is believed to help regulate body temperature and metabolic activity.

Within minutes of breathing the hydrogen sulfide and room-air cocktail, the mice stopped moving and appeared to lose consciousness, their respiration dropped from the normal 120 breaths per minute to fewer than 10 breaths per minute, and their core temperature dropped from the normal 37 degrees Celsius to as low as 11 C, depending on the controlled ambient temperature within the chamber.
Metabolic suspension was achieved through oxygen deprivation caused by exposure to gases such as hydrogen sulfide and carbon monoxide.
Known as oxygen mimetics, these chemicals are very similar to oxygen at the molecular level and so bind to many of the same receptor sites.
As a result, they compete for and interfere with the body's ability to use oxygen for energy production, a process called oxidative phosphorylation.
The inhibition of this function, in turn, is what the researchers believe causes the organism to shut down metabolically and enter a hibernation-like state.
Upon re-exposure to normal room air, the organisms quickly regained normal function and metabolic activity with no long-term negative effects.

If Roth and colleagues are able to replicate these findings in larger animal models, they foresee the first clinical use of this technology in humans could involve treating people suffering from severe fevers of unknown origin.

The National Institutes of Health and Fred Hutchinson Cancer Research Center funded this research.

Source: Fred Hutchinson Cancer Research Center, 2005


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