University of California

Robert H Schiestl

Jonathan Braun

Noriyuki Kasahara

Gay M Crooks

Katrin Hacke

Akos Szakmary

Bo Wei

Aya M Westbrook

Laura L Presley

Yelena O Rivina

James Borneman

Ramune Reliene

Mitsuko L Yamamoto

Michael E Jung

Robert Damoiseaux

Aaron Chapman

Daniel Malkin

Nikos Hontzeas

Kurt M Hafer

Jiri Aubrecht

Kasahara Noriyuki

A method of radiation-free hematopoietic stem cell (HSC) transplantation comprises administering to a mammalian subject one or two doses of 2 to 10 mg/kg body weight of a purine base analog, such as 6TG as a pre-conditioning step. The method further comprises engrafting into the subject hypoxanthine-guanine phosphoribosyltransferase (HPRT)-deficient donor HSCs within 48 to 72 hours of the pre-conditioning step; and administering to the subject about 1 to 5 mg/kg of the purine base analog every two to four days for two to eight weeks following the engrafting step. The method is performed in the absence of pre-conditioning via radiation. The subject is therefore not treated with myeloablative radiation in preparation for transplantation, and thus the subject is free of myeloablative radiation-induced toxicity.

Method for chemoselection

Inoculation of ATM-deficient mice with probiotic microorganisms, such as, changed immune parameters, decreased a marker of DNA damage and increased the lifespan of the mice. Compositions and methods described herein are useful for the treatment and prevention of Ataxia telangiectasia and other cancer-prone disease, such as p53 deficiency-associated cancers. Compositions and methods of the present invention are also useful for treating and preventing radiation-induced toxicity to normal tissue in a subject being exposed to radiation. Compositions and methods of the invention can increase lifespans in a simple, non-invasive manner.

Compositions and methods for promoting growth of beneficial microbes to treat or prevent disease or prolong life

Inoculation of ATM-deficient mice with probiotic microorganisms, such as, changed immune parameters, decreased a marker of DNA damage and increased the lifespan of the mice. Compositions and methods described herein are useful for the treatment and prevention of Ataxia telangiectasia and other cancer-prone diseases, such as p53 deficiency-associated cancers. Compositions and methods of the present invention are also useful for treating and preventing radiation-induced toxicity to normal tissue in a subject being exposed to radiation. Compositions and methods of the invention can increase lifespan in a simple, non-invasive manner.

The invention provides a method for detection of allergic inflammation in a subject that comprises assaying a test sample of peripheral blood from the subject for a marker of DNA damage. An elevated amount of marker present in the test sample compared to control sample is indicative of inflammation. The method can be adapted for quantitatively monitoring the efficacy of treatment of allergic inflammation in a subject. Markers of DNA damage include single- and/or double-stranded breaks in leukocytes, oxidative DNA damage in leukocytes, or a marker of nitric oxide oxidative activity (protein nitrosylation in leukocytes). This unexpected discovery of markers of systemic genotoxicity present in circulating leukocytes enables detection of allergic inflammation with a relatively simple and minimally invasive assay using peripheral blood.

Systemic genotoxicity as blood marker for allergic inflammation

Method for combined conditioning and chemoselection in a single cycle

The disclosure provides methods, systems, and kits for assaying an agent for mutagenic properties. The methods systems and kits utilize a DEL selectable marker and a colorimetric detection systems. Also included are methods systems and kits that utilize a DEL selectable marker and a regent that detects mitochondrial activity.

Assays for mutagenesis detection

Embodiments of the present invention provide compounds and compositions thereof, which are effective for mitigating tissue damage or lethality induced by an agent, and methods of making and using the same.

Compounds and compositions for mitigating tissue damage and lethality

The invention provides a method for detection of inflammatory disease in a subject that comprises assaying a test sample of peripheral blood from the subject for a marker of DNA damage. An elevated amount of marker present in the test sample compared to control sample is indicative of inflammatory disease activity, including sub-clinical inflammation. The method can be adapted for quantitatively monitoring the efficacy of treatment of inflammatory disease in a subject. Markers of DNA damage include single- and/or double-stranded breaks in leukocytes, oxidative DNA damage in leukocytes, or a marker of nitric oxide oxidative activity (protein nitrosylation in leukocytes). The inflammatory disease can be inflammatory bowel disease (ulcerative colitis or Crohn's disease). The invention may also be used for detection of other types of inflammatory disease, such as non-immune intestinal inflammatory disease (diverticulitis, pseudomembranous colitis), autoimmune diseases (rheumatoid arthritis, lupus, multiple sclerosis, psoriasis, uveitis, vasculitis), or non-immune lung diseases (asthma, chronic obstructive lung disease, and interstitial pneumonitis). This unexpected discovery of markers of genotoxicity present in circulating leukocytes enables detection of inflammation occurring at a localized site with a relatively simple and minimally invasive assay using peripheral blood.

Genotoxicity as a biomarker for inflammation

Growing community of inventors

Encino, CA, United States of America

Robert H Schiestl