NOBLE GAS NEUROPROTECTION AND NEUROREGENERATION FROM TREATMENT RELATED NEUROTOXICITY

Abstract

Disclosed are means of inducing neuroregeneration and/or neuroprotection in patients with damage to the nervous system. In one embodiment, Noble Gas containing compositions are administered to a patient suffering from a neurological injury, said therapy is administered alone, or in combination with other therapies useful in the induction of neuronal protection/stimulation of neurogenesis. In one specific embodiment, patients are treated with Noble Gas compositions to restore neural function subsequent to radiation therapy or chemotherapy for neoplasia of the brain. In another embodiment, Noble Gas compositions are administered prior to, concurrent with or after radiation and chemotherapy in order to induce a protective effect on non-malignant cells without substantially interfering with efficacy of radiation and chemotherapy.

Claims

1. A method of protecting non-neoplastic cells from cellular damaging effects of a brain cancer directed therapy, said method comprising the steps of: a) obtaining a Noble Gas composition with neuro protective and/or regenerative potential; and b) administering said composition in a manner to promote regeneration and/to provide selective protection of non-malignant tissue from effects of chemotherapy and/or radiation therapy.

2. The method of claim 1, wherein said brain cancer directed therapy comprises therapies selected from a group comprising of: a) radiation therapy; b) chemotherapy; c) surgery; d) metabolic therapy; e) targeted therapy, and f) immunotherapy.

3. The method of claim 1, wherein said Noble Gas composition is gas mixture containing oxygen and a proportion by volume of 20 to 70% of xenon.

4. The method of claim 3, wherein said proportion of xenon is between 22 and 60% by volume to oxygen.

5. The method of claim 4, wherein said proportion of xenon is between 25 and 60% by volume to oxygen.

6. The method of claim 1, wherein said noble gas containing mixture consists only of a) oxygen and xenon or b) air and xenon.

7. The method of claim 1, wherein said noble gas containing mixture also contains nitrogen, helium, Nitric Oxide, krypton, argon or neon.

8. The method of claim 1, wherein said noble gas containing mixture contains a proportion by volume of oxygen of between 15 and 25%.

9. The method of claim 1, wherein said noble gas containing mixture is supplied for inhalation from a pressurized container at a pressure greater than 2 bar.

10. The method of claim 1, wherein said noble gas containing mixture is administered intranasally.

11. The method of claim 1, wherein said noble gas containing mixture is administered through the use of a hyperbaric chamber.

12. The method of claim 11, wherein said hyperbaric chamber is pressurized to a pressure of no more than 3 atm (0.3 MPa).

13. The method of claim 12, wherein a noble gas is administered to the patient while the patient is in the hyperbaric environment.

14. The method of claim 1 wherein said noble gas is administered by inhalation or simulated inhalation.

15. The method of claim 1, wherein said noble gas is xenon, helium, or a mixture of xenon and helium.

16. The method of claim 1, wherein the noble gas is xenon or a mixture of xenon and helium, and the partial pressure of xenon is no more than about 0.8 atm (0.08 MPa).

17. The method of claim 1, wherein said noble gas is administered mixed with air, the air partial pressure being about 1 atm (0.1 MPa).

18. The method of claim 1, wherein said noble gas is administered as part of a gas mixture comprising oxygen, the nitrogen partial pressure in the mixture being equal to or less than about 0.8 atm (0.08 MPa).

19. The method of claim 18, wherein said gas mixture is essentially free of nitrogen.

20. The method of claim 19, wherein the oxygen partial pressure is about 0.2 atm (0.02 MPa).

Description

EXAMPLE

[0061] A clinical trial is conducted in 20 patients with brain metastasis who receive 2 Gy to 100 Gy fractionated over 2-8 weeks. 10 patients are treated with 10-20 liters of 30% xenon every other day during radiation exposure. An additional 10 patients are treated with similar radiation regimen and administered 10-20 liters of air every other day during radiation exposure. At 3, 8, 12, and 24 weeks, preservation in cognitive function as measured by HVLT-R Total Recall score (verbal learning and memory test) is observed in the xenon treated patients. Furthermore, verbal memory, as measured by the Hopkins Verbal Learning Test-Revised (HVLT-R), Cognitive flexibility as measured with the Controlled Oral Word Association (COWA), Word Fluency has measured with the Controlled Oral Word Association (COWA), Working memory has measured with the Wechsler Adult Intelligence Scale—Digit Span, Processing speed has measured with the Wechsler Adult Intelligence Scale—Digit Symbol, Motor dexterity has measured with the Grooved Pegboard (GP), Functional assessment, as measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br), all improved in the xenon treated group. No acceleration of tumor growth is seen in patients receiving xenon as compared to air controls.

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