AU2009304542A1

AU2009304542A1 - Use of tetrose to inhibit cancer and to increase cell viability

Info

Publication number: AU2009304542A1
Application number: AU2009304542A
Authority: AU
Inventors: Xingnong Wang; Youcheng Wei
Original assignee: Individual
Current assignee: Individual
Priority date: 2008-10-15
Filing date: 2009-10-08
Publication date: 2010-04-22
Also published as: WO2010043029A1

Description

WO 2010/043029 PCT/CA2009/001440 USE OF TETROSE TO INHIBIT CANCER AND TO INCREASE CELL VIABILITY FIELD The subject application relates to therapeutic uses of tetroses and compositions comprising tetroses. 5 BACKGROUND US Patent No. 7465734 Shephard, issued December 16, 2008 discloses the use of oxetanes as a constituent group of a prodrug. US Patent No. 6642205 Klyosov, issued November 4, 2003 discloses the use of tetroses as spacers in therapeutic compounds 10 PCT Patent Application W0040501 00 Berrada, filed December 3, 2003, discloses the use of combination of a chitosan and a salt of erythrulose or threose to treat a tumor. US Patent Application No. 9/830,912 Jariwalla, Filed Apr 30, 2001 discloses the use of threonate either alone or in combination with ascorbate, to promote 15 apoptosis. PCT Patent Application W007074344 Knox, Filed December 29, 2006, discloses the use of erythrose, erythrulose, and 3-hydroxy-2-butanone to assist processing of a prodrug. SUMMARY OF THE INVENTION 20 In a first embodiment, there is disclosed a method for inhibiting the growth of a cancer cell. The method may comprise directly or indirectly exposing the cancer cell to a pharmaceutically effective concentration of tetrose. In alternative embodiments, the tetrose may have a structural formula selected from the group consisting of: 1 WO 2010/043029 PCT/CA2009/001440

C

4

H

8 0 4 H 0 H 0 C CH2OH C I I H-C-OH C=O HO-C-H I I H-C-OH H-C-OH H-C-OH I I CH2OH CH2OH CH2OH

C

4

H

6 0 4 H 0 H 0 H O H 0 H 0 C C C C C H-C-OH I I I II C=O O=C H-C-OH HO-C-H H-C-OH I I I II H-C-OH H-C-OH C=O C=O C I I I 1I11, lk CH2OH COH2OH CH2OH CH2OH H 0 H 0 C H 0 H 0 H 0 H o0 HO -C -H IiI H-C-OH C-OH HO-C H-C-OH HO-C-H H I I I I C C-OH C-OH C-OH C-OH I I II II 0 H CH2OH CH2OH CHOH CHOH

C

4

H

8 0 3 H 0 H O H 0 H O H 0 C C C C C I0 NI I,, N I 4pI I I I I I H-C-OH H-C-H H-C-H H-C -H H-C-OH I I I I I Hi-CO - - OH rir H-CL,-H H-C% - H H-CL;-OH CH2OH CH2OH CH2OH CH2OH CH3 H 0 C HO - C - H H- C - OH CH3 2 WO 2010/043029 PCT/CA2009/001440

C

4

H

6 0 3 H 0 H O H 0 H 0 C C C C C=0 O=C H-C-H H-C-H I I I I H-C-H H-C-H C=O C=0 I I I I CH2OH CH2OH CH2OH CH2OH H 0 H O H 0 H 0 C C C C N| | 1.- |0 o H-C -H H-C-H H-C -OH HO-C-H I I I I H-C-OH H-C-OH H-C-H H-C-H I I N I C C C C H 0 0 H H 0 0 H H 0 H O H 0 H 0 C C C C | I I I C-H C-H C-OH C-OH CH2OH CH2OH CH2OH CH2OH

C

4

H

4 0 4 H 0 H O H 0 H 0 H 0 C C C C C C=O 0 =C H-C-OH II I I C=0 O=C H-C-OH H-C-OH C=O I I I II C=0 C=O C C C I IN CH2OH CH2OH H 0 H 0 H 0 H 0 C HO -C - H C=0 C H 0 3 WO 2010/043029 PCT/CA2009/001440

C

4

H

4 0 3 H 0 H O H 0 H 0 H 0 C C C I I Io Nl10 C C 0=0 0 =0 H-C-H II | C=0 O=C H-C-H H-C-H C= II I C=0 C=0 C C C C I / CH3 CH3 H 0 H 0 H 0 H 0 C H-C -H C=0 C H 0

C

4

H

6 0 2 H 0 H 0 H 0 H 0 H 0 C C C C c H-C-H 0=0 0=0 H-C-H H-C -H H-C-H I I I I H-C-H H-C-H C=0 0=0 C CH3 CH3 CH3 CH3 H 0 H 0 H\ //0 C H-C -H H-C -H C 0 H 4 WO 2010/043029 PCT/CA2009/001440

C

4

H

8 0 2 H 0 H O H 0 H O H 0 H 0 C C C C C C II I III H-C-OH HO-C-H H-C-H H-C-H H-C-H H-C-H I I I I I I H-C-H H-C-H H-C-OH H-C-OH H-C-H H-C-H I I | I CH3 CH3 CH3 CH3 CH2OH CH2OH and any pharmaceutically effective derivatives thereof. In alternative embodiments, the derivative may be a conjugated, substituted, ionised, salt, isomeric, acid, base, aldehyde, ketone, alcohol, amine, amide, thiol, 5 ring or linear form. In alternative embodiments the tetrose may be selected from the group consisting of erythrose, threose and erythrulose. In alternative embodiments, the indirect exposing may comprise exposing the cancer cell to a prodrug metabolisable to release tetrose. 10 In alternative embodiments the cancer cell may be exposed to a concentration of greater than about 100 mg/litre of tetrose and exposed to a glucose concentration of greater than about 500 mg/litre before or simultaneous with the exposure to tetrose. In alternative embodiments, the cancer may be selected from the group consisting 15 of carcinoma, sarcoma, adenoma, leukemia, lymphomas and myeloma. In alternative embodiments, the exposure may occur in combination with exposing the cell to a modulator of carbonic anhydrase activity. In alternative embodiments, the modulator may comprise a Zinc salt. 5 WO 2010/043029 PCT/CA2009/001440 In alternative embodiments, there is disclosed a method for improving the viability of a cell, the method may comprise directly or indirectly exposing the cell to a therapeutically effective amount of tetrose. In alternative embodiments, the derivative may be a conjugated, substituted, 5 ionised, salt, isomeric, acid, base, aldehyde, ketone, alcohol, amine, amide, thiol, ring or linear form. In alternative embodiments, the exposure may occur in combination with exposing the cell to a modulator of carbonic anhydrase activity. The cell may be under conditions of limited energy supply and may have a mitochondrial disorder. 10 In alternative embodiments, the tetrose may be selected from the group consisting of erythrose, threose and erythrulose. In alternative embodiments, indirect exposing may comprise exposing the cell to a prodrug metabolisable to release tetrose. In alternative embodiments, the methods of embodiments may comprise exposing 15 the cells to a concentration of between about 1 mg/litre and about 200 mg/litre of the tetrose to increase the viability of cell. In alternative embodiments, the mitochondrial disorder may be associated with a disorder selected from the group consisting of neurodegenerative disease, Alzheimer's disease, Parkinson's disease, Huntington's disease, cardiovascular 20 disease, stroke, obesity, diabetes, multiple sclerosis, systemic lupus erythematosis, rheumatoid arthritis, schizophrenia, bipolar disorder, depression, ataxia, autism, epilepsy, migraine, Batten disease, Lactic acidemia, Leber's disease, mitochondrial cardiomyopathy and myopathy, paraplegin, NASH, and Wilson's disease. 25 In alternative embodiments, there is disclosed a method of treating a mitochondrial disorder in a subject having such disorder, the method may 6 WO 2010/043029 PCT/CA2009/001440 comprise directly or indirectly administering to the subject a pharmaceutically effective dose of tetrose. In a further embodiment there is disclosed a composition which may comprise a direct or indirect source of tetrose in an amount effective to inhibit the growth of a 5 cancer cell; and a pharmaceutically acceptable carrier or diluent. In a further embodiment there is disclosed a composition which may comprise a direct or indirect source of tetrose in an amount effective to increase the viability of a cell having a mitochondrial disorder; and a pharmaceutically acceptable carrier or diluent 10 In a further embodiment there is disclosed the use of an effective dose of a direct or indirect source of tetrose to achieve an effect selected from the group consisting of: inhibiting the growth of a cancer cell; increasing the viability of a cell under low energy conditions; and increasing the viability of a cell having a mitochondrial disorder. 15 In a further embodiment there is disclosed the use of a prodrug to manufacture a dietary supplement. In a further embodiment there is disclosed a composition which may comprise a prodrug metabolisable to yield a pharmaceutically effective amount of tetrose. In a further embodiment there is disclosed the use of tetrose to manufacture a 20 medicament for: inhibiting the growth of a cancer cell; or improving the viability of a cell exhibiting a mitochondrial disorder. Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples while indicating 25 preferred embodiments of the invention are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. 7 WO 2010/043029 PCT/CA2009/001440 DETAILED DESCRIPTION OF THE INVENTION Definitions In this disclosure the term "in combination with" means that the elements or procedures to be combined may be mixed, or may be used simultaneously, or 5 sequentially, or in any other way temporally, spatially or otherwise combined. In this disclosure an "effective amount" of a compound means a therapeutically effective amount, a prophylactically effective amount, or a nutritionally effective amount as the case may be or as the context requires. In embodiments a therapeutic, nutritional or prophylactic result may comprise stopping or slowing or 10 preventing the progress of a disease; and may include inhibiting growth of or division of cancer cells, or increasing tumor apoptosis, or causing the shrinking, or disappearance of a tumour. Those skilled in the art will recognise that what constitutes an "effective amount" of a compound may very according to a variety of factors including but not limited to the nature and extent of progression of a 15 disease state, and the age, sex, and weight of the subject. In embodiments "effective amounts" may be comprised in one or more dosages of the same or different types or quantities, spread over a desired time period, and may be adjusted as necessary in ways readily apparent to one skilled in the art. It will be understood that those skilled in the art will avoid dosages and combinations that 20 would cause unacceptable deleterious effects on the subject. In this disclosure a "cell" or "tissue" may be isolated, may be comprised in group of cells, may be in culture, or may be comprised in a living subject and may be a mammalian cell and may be a human cell. In this disclosure "cancer" "means and includes any malignancy, or malignant cell 25 division or malignant tumour, or any condition comprising uncontrolled or inappropriate cell proliferation and includes without limitation any disease characterized by uncontrolled or inappropriate cell proliferation. In embodiments cancers cells may exhibit mitochondrial disorders, deficiencies or dysfunctions. In embodiments cancer may include but is not limited to carcinomas, sarcomas, 8 WO 2010/043029 PCT/CA2009/001440 adenoma, leukemias, lymphomas and myelomas. In particular embodiments a cancer may include carcinoma, adenocarcinoma, adenoma, sarcoma, lymphoma, and leukemia. In particular embodiments a cancer may be or may include Bladder Cancer, Breast Cancer, Colon and Rectal Cancer, Endometrial Cancer, Kidney 5 (Renal Cell) Cancer, Leukemia, Lung Cancer, Melanoma, Skin Cancer (Nonmelanoma), Non-Hodgkin Lymphoma, Pancreatic Cancer, Prostate Cancer, Thyroid Cancer, Stomach Cancer, Liver Cancer, Ovarian Cancer. In particular embodiments cancer may be Adrenal Cancer, Anal cancer, Aplastic Anemia, Bile Duct Cancer, Bladder Cancer, Bone Cancer, Brain Cancer, Breast Cancer, 10 Bronchus and Lung Cancer, Central Nervous System Cancer, Cervical Cancer, Colon and Rectum Cancer, Connective Tissue Cancer, Cranial Nerves Cancer, Digestive organs Cancer, Endometrial Cancer, Endocrine Cancer, Esophageal Cancer, Ewing's Family of Tumors, Gallbladder Cancer, Gastrointestinal Carcinoid Tumors, Gastrointestinal Stromal Tumors, Gestational Trophoblastic Disease, 15 Head and Neck Cancer, Hodgkin Lymphoma Cancer, Kaposi's Sarcoma, Kidney Cancer, Laryngeal and Hypopharyngeal Cancer, Larynx Cancer, Leukaemia Cancer, Leukaemia - Lymphoid Cancer, Leukaemia - Myeloid Cancer, Leukaemia of Unspecified Cell Type Cancer, Lip Cancer, Liver Cancer, Lung Carcinoid Tumors, Lymphoid, Haematopoietic and Related Tissues Cancer, Lymphoma 20 Cancer, Malignant Immunoproliferative Cancer, Malignant Neoplasm Cancer, Malignant Neoplasm of Genital Organs Cancer, Malignant Neoplasm of Urinary Tract Cancer, Meninges Cancer, Mesothelioma Cancer, Multiple myeloma Cancer, Myelodysplastic Syndrome, Nasal Cavity and Middle Ear Cancer, Nasopharyngeal Cancer, Nasopharynx Cancer, Neuroblastoma, Non-Hodgkin's 25 Lymphoma Cancer, Non-Hodgkin's lymphoma, Other and Unspecified Cancer, Neuroblasma, Oral Cavity and Oropharyngeal Cancer, Osteosarcoma, Oropharynx Cancer, Ovarian Cancer, Pancreas Cancer, Parathyroid Cancer, Penis Cancer, Peripheral and Cutaneous T-cell Lymphomas Cancer, Peripheral Nerves Cancer, Peritoneum Cancer, Pharyngeal Cancer, Pituitary Tumor, 30 Postcricoid Region Cancer, Prostate cancer, Retinoblastoma, Rhabdomyosarcoma, Salivary Glands Cancer, Sarcoma, Soft Tissue Cancer, Melanoma Skin Cancer, Nonmelanoma Skin Cancer, Sinus Cancer, Small 9 WO 2010/043029 PCT/CA2009/001440 Intestine Cancer, Small Intestine Cancer, Stomach Cancer, Testicular Cancer, Thymoma and Thymic Carcinoma, Thyroid Cancer, Tongue Cancer, Tonsil Cancer, Trachea Cancer, Cancer NOS, Urinary Organs Cancer, Urethral cancer, Uterine Cancer, Uterine Sacrcoma, Vaginal Cancer, Vulvar Cancer, Cancer of 5 Unknown Primary, Waldenstr6m macroglobulinemia, and Wilms Tumour. In particular embodiment the cancer may be Bladder, Brain, Breast, cervical, Colorectal, uterine, Esophagus, Hodgkin lymphoma, Kidney, Larynx, Leukaemia, Lip, Lung, Multiple myeloma, Non-Hodgkin lymphoma, Oral cavity, Ovary, Pancreas, Prostate, Skin, Stomach, Testicular, or Thyroid cancer. In particular 10 embodiment the cancer may be Stomach Cancer, Lung and Bronchus Cancer, Liver Cancer, Esophageal Cancer, Breast Cancer, Colon and Rectal Cancer, Prostate Cancer, Cervical Cancer, Uterine Cancer, Oral Cancer, Sarcoma, Bladder Cancer, Melanoma, Ovarian Cancer, Endometrial Cancer, Pancreas Cancer, Kidney (Renal Cell) Cancer, Lymphoma, or Leukemia. In particular 15 embodiments the cancer may be ductal carcinoma, glioblastoma, epithelioid carcinoma, adenocarcinoma, carcinoma, or erythroleukemia, In this disclosure the term "nutritional supplement" means a preparation intended to provide supplementary nutrients that are not present in sufficient quantity or desired quantity in a subject's diet. 20 In this disclosure the terms "directly exposing", "directly administering" and the like, a cell or tissue to tetrose, means that the cell or tissue is exposed to a composition or medium, which may without limitation be a fluid, comprising free tetrose. In this disclosure the terms "indirectly exposing", "indirectly administering" or the 25 like of a cell or tissue to tetrose means that the cell or tissue is exposed to a prodrug or other composition that is metabolisable to release a pharmaceutically effective amount of free tetrose. In this disclosure the term "modulator" means a chemical whose presence modifies the behaviour of an enzyme, which may be a carbonic anhydrase 10 WO 2010/043029 PCT/CA2009/001440 enzyme. In embodiments a modulator may be or may comprise Zinc, or a zinc salt, or a carbonic anhydrase inhibitor. In this disclosure the term "prodrug" means an inactive form of tetrose, that is or may be converted into an active form of tetrose by normal metabolic processes. 5 Without limitations, an active form of tetrose may be or may comprise a free tetrose monosaccharide. It will be understood that an "inactive form" of tetrose means a form of tetrose that is not directly metabolically available to a cell and in embodiments inactive tetrose may be or may include tetrose that is conjugated, modified, derivatised, complexed, isomerised or in any other form, 10 which can be converted to an active form of tetrose by a cell. In particular embodiments a prodrug may be or may comprise any metabolisable disaccharide or polysaccharide form of tetrose that is metabolised to release active tetrose. A wide range of alternative prodrug forms of tetrose will be readily recognised, selected among, synthesised and used by those skilled in the art. In particular 15 embodiments a prodrug may be or may comprise heptose, sedoheptulose, mannoheptulose, ascorbate, or Vitamin C and in embodiments may be used to treat non-cancerous conditions. In embodiments the prodrug may be or may comprise heptose, may comprise a monosaccharide having the molecular formula

C

7

H

14 0 7 and may be or may comprise sedoheptulose, mannoheptulose. In 20 particular embodiments any one or more compounds in the foregoing definition may be excluded. In particular embodiments, which may be embodiments for the treatment of cancer, such excluded compounds may be or may comprise mannoheptulose, Vitamin C and ascorbate. In this disclosure a "limiting supply" or "limited availability" and similar terms, of a 25 sugar or other chemical or substrate or of energy supply, means circumstances wherein the supply of a suitable metabolisable chemical has the effect of limiting the growth or viability of the cell or the normal chemical and physical processes of the cell or wherein the cell is unable to utilise available substrates effectively to maintain a suitable energy supply. Similarly "glucose deficiency" means that a cell 30 has a low internal glucose concentration that may arise from causes including low glucose supply or deficient ability to absorb glucose or metabolise other chemicals 11 WO 2010/043029 PCT/CA2009/001440 to liberate intracellular glucose. Similarly "energy deficiency" and similar terms mean that the cell is unable to maintain a suitable energy supply because of glucose deficiency or because of an inability to properly or efficiently use glucose or ketone bodies, or pyruvate or their metabolites to generate energy, as the case 5 may be. In this disclosure the term "mitochondrial disorder" means any condition or disorder which is partly or wholly, directly or indirectly caused by mitochondrial deficiency or dysfunction and in alternative embodiments may include but is not limited to cancer, aging and neurodegenerative disease. In embodiments 10 mitochondrial disorders may be characterised by inability of cells to properly or efficiently use glucose or ketone bodies, or pyruvate or their metabolites to generate energy. Without limitation such diseases may include but are not limited to Alzheimer's disease, Parkinson's disease, Huntington's disease, cardiovascular disease, stroke, obesity, diabetes, multiple sclerosis, systemic lupus 15 erythematosis, rheumatoid arthritis, schizophrenia, bipolar disorder, depression, ataxia, autism, epilepsy, migraine, Batten disease, Lactic academia, Leber's disease, mitochondrial cardiomyopathy and myopathy, paraplegin, Nonalcoholic steatohepatitis (NASH), and Wilson's disease. In this disclosure the term "inhibit" where used with reference to cancer cells or 20 the growth or development thereof, means and includes any effects that result in or comprise slowing or preventing growth or cell division of the cells, killing the cells, disabling the cells, and in any way reducing the viability, rate of division or longevity of the cells. In this disclosure the term "tetrose" means without limitation, pharmaceutically 25 effective monoshaccharides with the molecular formula C 4

H

8 0 4 or that are otherwise represented by any of the structural formulae set out in Table A and without limitation may include any pharmaceutically effective derivatives of any of the foregoing including without limitation any conjugated forms, substituted forms, ionised forms, salts and isomers including D and L stereoisomers, and any acid, 30 base, aldehyde, ketone, alcohol, amine, amide, thiol, ring and linear forms of any 12 WO 2010/043029 PCT/CA2009/001440 of the foregoing. In particular embodiments "tetrose" may be or may include erythrulose, erythrose, threose, deoxy-tetrose, dehydro-tetrose, and deoxy dehydro-tetrose and any D and L isomers thereof. In embodiments, tetrose may be or comprise erythrose, erythrulose or threose, and in selected embodiments 5 may be or may comprise D-erythrose, L-erythrose, D-threose, L-threose, D erythrulose or L-erythrulose. In particular embodiments tetroses may be pure or may be substantially pure or may comprise mixtures of one or more tetroses. Tetroses, derivatives thereof, and prodrugs comprising the foregoing, can be prepared by conventional methods well known to those skilled in the art, who will 10 readily identify, select and utilise suitable tetroses for particular purposes. Table A: Illustrative non-limiting examples of tetroses:

C

4

H

8 O4 H 0 H 0 C CH2OH C H-C-OH C=O HO-C-H H-C-OH H-C-OH H-C-OH CH2OH CH2OH CH2OH

C

4

H

6 0 4 H 0 H 0 H O H 0 H 0 C C C C C H-C-OH I I I I H -C -O C=O O=C H-C-OH HO-C-H H-C-OH I I I I H-C-OH H-C-OH C=0 C=O C I 1 I0 Ik CH2OH CH2OH CH2OH CH2OH H 0 H 0 C H H 0 H 0 H 0 HO - C - H C C H-C-OH C -OH HO -C H -C -OH HO -C - H C C-OH C-OH C-OH C-OH 4PI I |1 || 0 H CH2OH CH2OH CHOH CHOH 13 WO 2010/043029 PCT/CA2009/001440

C

4

H

8 0 3 H 0 H O H 0 H O H 0 C C C C C I I I II H-C-H H-C-H H-C-OH HO-C-H H-C-OH I I I II H-C-OH H-C-OH H-C-H H-C-H H-C-OH CH2OH CH2OH CH2OH CH2OH CH3 H 0 C HO -C - H H -C- OH CH3

C

4

H

6 0 3 H o0 H 0 H 0 H 0 C C C C I I I I C=O O=C H-C -H H -C -H I I I I H-C-H H -C-H C=O C=O I I I I CH2OH CH2OH CH2OH CH2OH H 0 H O H 0 H 0 C C C C H-C-H H-C-H H-C -OH HO-C-H I I I I C C C C H 0 0 H H 0 0 H H 0 H 0 H 0 H o0 C C C C C-H C-H C-OH C-OH I I I I CH2OH CH2OH CH2OH CH2OH 14 WO 2010/043029 PCT/CA2009/001440

C

4

H

4 0 4 H 0 H OH 0 H 0 H 0 C C C I I I CH2OH CH2OH H 0 H 0 H O H O C HO -C - H C=O C H 0

C

4

H

4 0a H 0 H O H 0 H 0 H 0 C C C C C C=0 0 =0 H-C-H 4pI I I I C=0 0=0 H-C-H H-C-H C=0 I I I I I C=0 C=0 C C C CH3 CH3 H 0 H 0 H 0 H 0 C H-C -H 0=0 C / % H 0 15 WO 2010/043029 PCT/CA2009/001440

C

4

H

6 0 2 H 0 H 0 H 0 H H 0 C C C C C H-C-H I I I I I C=O O=C H-C-H H-C-H H-C-H H-C-H H-C-H C=O C=O C I I I I CH3 CH3 CH3 CH3 H 0 H 0 C H-C -H H-C -H C O H

C

4

H

8 0 2 H 0 H O H 0 H O H 0 H 0 C C C C C C II I I I I H-C-OH HO-C-H H-C-H H-C-H H-C-H H-C-H I I I I I I H-C-H H-C-H H-C-OH H-C-OH H-C-H H-C-H I I I I I I CH3 CH3 CH3 CH3 CH2OH CH2OH For greater certainty and without limitation, in particular embodiments any one or more compounds in the definition of tetrose may be excluded and in particular embodiments such excluded tetroses may be or may comprise one or more of 5 threonate, erythrose-4-phosphate, acetoacetate, sodium butyrate, succinic acid, and D-beta-hydroxybutyrate. It will be understood that the tetrose used in particular embodiments may be used in combination with suitable pharmaceutically acceptable carriers or excipients and may be used in any suitable dosage forms. Those skilled in the art will readily 10 identify, select from, and use the foregoing to suit the circumstances in question. 16 WO 2010/043029 PCT/CA2009/001440 Where the cell to be treated is comprised in the body of a subject the methods disclosed may be implemented and the compositions disclosed may be delivered to the cell in any conventional ways including without limitation the delivery of the tetrose or prodrug, orally, parentally, enterally, intramuscularly, subcutaneously, 5 intravenously, or by inhalation and may be delivered in combination with suitable carriers or excipients, in suitable dosage forms including without limitation tablets, capsules, subdermal pumps or other routes useful to achieve an effect. Alternative delivery methods may include osmotic pumps, implantable infusion systems, intravenous drug delivery systems, and refillable implantable drug 10 delivery systems. Delivery by inhalation may comprise delivery using nebulizers, metered dose inhalers, powder inhalers, all of which are familiar to those skilled in the art. Suitable methods, compositions and routes of delivery will be readily recognised and implemented by those skilled in the art. Embodiments: 15 First embodiment: In a first embodiment there is disclosed a method for inhibiting the growth of cancer cells comprising directly or indirectly exposing said cancer cells to a pharmaceutically effective concentration of tetrose. In embodiments the tetrose may be or may comprise erythrose, erythrulose or threose, and in selected embodiments may be or may comprise D-erythrose, L-erythrose, D-threose, L 20 threose, D-erythrulose, L-erythrulose, and in particular examples the tetrose may be D-erythrose, D-threose, or L-erythrulose In alternative embodiments there is disclosed the use of tetrose to inhibit the growth of cancer cells. In embodiments cells may be exposed to the tetrose at a concentration of from at least about 1 00mg/litre up to about 1000 mg/litre or more. In alternative 25 embodiments the cells may be exposed to the tetrose at a concentration of at least about 100 mg/litre, or at least about 200 mg/litre, at least about 300 mg/litre, at least about 400 mg/litre, at least about 500 mg/litre, at least about 600 mg/litre, at least about 700 mg/litre, at least about 800 mg/litre, at least about 900 mg/litre, at least about 1000 mg/litre or more. In embodiments the tetrose may be applied 30 to cells under conditions where the cells are simultaneously exposed to glucose at 17 WO 2010/043029 PCT/CA2009/001440 a concentration of greater than about 600 mg/litre, greater than about 700mg/litre, greater than about 800mg/litre, greater than about 900mg/litre, or greater than about 1 000mg/litre. In one alternative embodiment the tetrose may be D erythrose, which may be used at a concentration of between about 200mg/litre 5 and about 1 000mg/litre or between about 500 mg/litre and about 1 000mg/litre. In embodiments the D-erythrose or other tetrose may be used at concentrations above 1 000mg/litre. It will be understood that the specific dosage desirable or suitable will vary depending on a variety of factors including but not limited to the disease to be 10 treated, weight, sex, metabolism of the subject and the specific tetrose or composition being applied. Where the tetrose is D-erythrose and is applied at a concentration of between about 200 mg/litre and about 1000mg/litre, then in some cases an accompanying glucose concentration of greater than about 500 mg/litre, 600mg/litre, 700 mg/litre, 800mg/litre, 900mg/litre or greater than about 1000 15 mg/litre may be required in order to obtain a desired effect on cell growth. In particular embodiments lower glucose levels or more severely limited availability of glucose or energy supply may require increased levels of tetrose to inhibit the growth of cancer cells. In particular embodiments an effective dose of a selected tetrose may comprise 20 up to about 0.1 gram of tetrose per kg body weight of a subject or may comprise up to about 0.5g/kg body weight of the subject, up to about 1 g/kg body weight of the subject or up to about 2g/kg; or up to about 3g/kg, or up to about 4g/kg, or up to about 5g/kg, or up to about 1og/kg body weight of the subject, or more. In embodiments an effective dose of a selected tetrose may comprise up to about 25 0.5g, 1.0g, 1.5g or up to about 2.Og of tetrose per kg body weight of a subject. In alternative embodiments the tetrose or combination thereof may be administered in a solution of up to about 1% or up to about 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 35%, 40%, 45%, 50% or greater than 30 about 50% concentration by weight. In embodiments the tetrose or combination thereof may be administered in a solution containing up to about 16% to 40% 18 WO 2010/043029 PCT/CA2009/001440 tetrose. In alternative embodiments the compositions may be administered to a subject continuously, once a day, twice a day, three times a day, four times a day, at least about once an hour, or more or less frequently. In embodiments the tetrose may be administered to a subject twice a day or three times a day. In 5 embodiments the tetrose may be administered at least about 1, 2, 3, 4, 5, 6 or more times a day, or at least 1,2,3,4,5,6 or more times a week, and may be administered alone or in combination with other active or inactive agents. In embodiments the tetrose may be administered to a subject for 1, 2, 3, 4, 5, 6 or more days continuously. 10 In alternative embodiments of the first embodiment, the tetrose may be selected from the group consisting of erythrose, threose and erythrulose and isomers thereof. In further alternative embodiments of the first embodiment indirect exposing may comprise administering a prodrug. In alternative embodiments the cancer cells may be exposed to a concentration of greater than about 1 00mg/litre, 15 200mg/litre, 300 mg/litre, 400mg/litre, 500mg/litre, 600mg/litre, 700mg/litre, 800mg/litre, 900mg/litre or more than about 1000 mg/litre of tetrose, or may be exposed to a glucose concentration of greater than about 500 mg/litre before or simultaneous with said exposure to tetrose. Second embodiment: In a second embodiment there is disclosed a method for 20 improving the viability of a cell, the method comprising directly or indirectly exposing said cell to a therapeutically effective amount of tetrose. There is also disclosed the use of tetrose for improving the viability of a cell. In embodiments the cell may be unable to use glucose to maintain cell viability, or may be subject to conditions of low energy supply or glucose or energy deficiency or may have a 25 mitochondrial disorder. In further embodiments there is disclosed a method of treating a mitochondrial disorder or compensating the energy deficiency in a cell comprising directly or indirectly supplementing the nutrient supply to said cell with an effective dose of tetrose. Tetrose may be an effective energy source for mammalian cells under conditions 30 wherein the cells are unable to use glucose to maintain cellular functions. Suitable 19 WO 2010/043029 PCT/CA2009/001440 conditions for the use of tetrose as an energy source for cells may include conditions wherein the cells are unable to use glucose efficiently, such as mitochondrial deficiency/dysfunction, infection with virus or bacteria, or other medical conditions resulting in low cellular energy generation or abnormal cellular 5 energy generation, including without limitation extreme high anaerobic glycolysis. In particular embodiments the tetrose may be or may comprise erythrose, erythrulose or threose, and in selected embodiments may be or may comprise D erythrose, L-erythrose, D-threose, L-threose, D-erythrulose, L-erythrulose, and in particular examples the tetrose may be D-erythrose or L-erythrulose. In particular 10 embodiments the tetrose may be D-erythrose and may be applied to the cells at a concentration of about 1-200 mg/litre and may be applied at concentrations of up to about 20 mg/litre, up to about 40 mg/litre, up to about 60 mg/litre, up to about 80 mg/litre, up to about 100 mg/litre, up to about 200 mg/litre, up to about 300 mg/litre, up to about 400 mg/litre, up to about 600 mg/litre, up to about 800 15 mg/litre, up to about 1 000mg/litre or more than about 1 000mg/litre. In alternative embodiments the cells may be exposed to tetrose at any concentration and in any form sufficient to adjust the ATP or pH homeostasis of the targeted cells to support cellular function, which concentrations and forms will be readily determined by those skilled in the art using known procedures. 20 In embodiments improving the viability of cells may comprise improving mitochondrial function in the cells, which may be achieved by exposing the cells to tetrose in combination with other pharmaceutically active compounds that will be readily identified, selected from and utilised by those skilled in the art. In particular embodiments tetrose may be delivered or used in combination with one or more 25 compounds that may include but are not limited to DCA (dichloroacetate), ginkgo biloba extract, hydroxytyrosol, and resveratrol. In alternative embodiments of the second embodiment the cell may be exposed to conditions of energy limitation. In alternative embodiments of the second embodiment the cell may have a mitochondrial disorder. In alternative 30 embodiments tetrose may be selected from the group consisting of erythrose, threose and erythrulose. In alternative embodiments of the second embodiment 20 WO 2010/043029 PCT/CA2009/001440 the method may comprise exposing said cells to a concentration of between about 1 mg/litre and about 1000 mg/litre of tetrose. In embodiments the method may comprise exposing the cells to a concentration of between about 1 mg/litre and about 200 mg/litre of tetrose. 5 In alternative embodiments of the second embodiment the mitochondrial disorder may be associated with a disorder selected from the group consisting of neurodegenerative disease Alzheimer's disease, Parkinson's disease, Huntington's disease, cardiovascular disease, stroke, obesity, diabetes, multiple sclerosis, systemic lupus erythematosis, rheumatoid arthritis, schizophrenia, 10 bipolar disorder, depression, ataxia, autism, epilepsy, migraine, Batten disease, Lactic acidemia, Leber's disease, mitochondrial cardiomyopathy and myopathy, paraplegin, NASH, and Wilson's disease. In a further alternative embodiment of the second embodiment there is disclosed a method of treating a mitochondrial disorder in a subject having such disorder, the 15 method comprising directly or indirectly administering to the subject an effective dose of tetrose. In a further embodiment there is disclosed the use of tetrose to treat a mitochondrial disorder, or to treat other medical conditions which may include without limitation conditions of energy deficiency. Third embodiment: 20 In a third embodiment there are disclosed compositions comprising a pharmaceutically acceptable carrier or diluent and a direct or indirect sources of tetrose in amounts effective to inhibit the growth of a cancer cell or to increase the viability of a cell under conditions of low energy supply; or to increase the viability of a cell having a mitochondrial disorder. 25 In alternative embodiments there is disclosed a composition comprising: a direct or indirect source of tetrose in an amount effective to inhibit the growth of cancer cells; and a pharmaceutically acceptable carrier or diluent. In alternative embodiments the compositions disclosed may comprise a direct or indirect source 21 WO 2010/043029 PCT/CA2009/001440 of tetrose in an amount effective to increase the viability of a cell having a mitochondrial disorder; and a pharmaceutically acceptable excipient. Fourth embodiment: In any embodiment there are disclosed compositions comprising a prodrug 5 metabolisable to yield a pharmaceutically effective amount of tetrose. In alternative embodiments there are disclosed compositions comprising a prodrug metabolisable to yield a pharmaceutically effective amount of tetrose and in alternative embodiments there is disclosed the use of the prodrug to manufacture a dietary supplement, to inhibit the growth of cancer cells; to increase the viability 10 of cells under low energy conditions; and to increase the viability of cells having a mitochondrial disorder. In alternative embodiments there is disclosed the use of an effective dose of a prodrug metabolisable to yield tetrose to achieve an effect selected from the list consisting of: inhibiting the growth of cancer cells; increasing the viability of cells 15 under low energy conditions; and increasing the viability of cells having a mitochondrial disorder. In alternative embodiments there is disclosed the use of a tetrose containing prodrug to manufacture a dietary supplement. In embodiments the prodrug may be or may comprise heptose, may comprise a monosaccharide having the molecular formula C 7

H,

4 0 7 and may comprise sedoheptulose, 20 mannoheptulose, vitamin C or ascorbate. Fifth embodiment: In an embodiment there are disclosed methods of increasing the viability of a cell under limited energy supply and methods of inhibiting the growth of a cancer cell. The methods may comprise directly or indirectly exposing the cell to tetrose in the 25 presence of compounds known to enhance intracellular carbonic anhydrase activity or otherwise modulate cellular or extracellular enzymes. In embodiments the compound may be or may comprise a pharmaceutically acceptable zinc salt which may be zinc Chloride, zinc sulfate, zinc acetate, zinc monomethionine, zinc gluconate, a zinc salt of an amino acid, such as: zinc glutamate, zinc aspartate, a 22 WO 2010/043029 PCT/CA2009/001440 zinc salt of an organic acid, such as zinc oxaloacetate, zinc malate, zinc fumarate, zinc succinate, a zinc salt of a monosaccharide acid, zinc ascorbate, or in any other form readily taken up by a cell, all of which will be readily identified, understood, selected from and utilised by those skilled in the art. In embodiments 5 cells may be exposed to the zinc at a concentration of from at least about 5pM, 10pM, 15pM, 20pM, 25pM, 30pM, 35pM, or more up to about 40pM or more. Suitable concentrations will be readily identified, selected from and utilised by those skilled in the art. Sixth Embodiment: 10 In an embodiment there are disclosed methods of increasing the viability of a cell under limited energy supply and methods of inhibiting the growth of a cancer cell. The methods may comprise directly or indirectly exposing the cell to tetrose in the presence of compounds known to inhibit extracellular carbonic anhydrase activity. In embodiments the compound may be or may comprise quaternary ammonium 15 sulfanilamide, or may comprise other suitable carbonic anhydrase inhibitors, all of which will be readily identified, selected from and used by those skilled in the art. In embodiments the carbonic anhydrase inhibitor may be a compound to which the cell membrane is partially or wholly impermeable. Where the compound is ammonium sulfanilamide it may be provided to a subject in amounts of from 20 125mg to 1000mg one to four times a day. Seventh Embodiment: In an embodiment there are disclosed methods of increasing the viability of a cell under limited energy supply. The methods may comprise directly or indirectly exposing the cell to tetrose in the presence of a compound or composition known 25 to enhance mitochondrial function. In particular embodiments these may be or may comprise without limitation dichloroacetate, ginkgo biloba extract, hydroxytyrosol, reservatrol, ascorbic acid, ascorbate. A wide range of suitable compounds and preparations will be readily recognised, selected from and used by those skilled in the art. 23 WO 2010/043029 PCT/CA2009/001440 EXAMPLES The following examples are presented for the purpose of illustrating embodiments and are not limiting. Methods 5 Cell Culture: Cell lines are cultured in cell culture incubator in media of DMEM or RMPI 1640 with different concentrations of glucose, D-erythrose, L-erythrulose, D threose, ZnCl 2 and 10% FBS. Trypan-Blue assay: Cell number and viability was determined using a standard Trypan-Blue assay counted on a hemocytometer. 10 MTT assay: It measures the special activity of mitochondria to cleave the tetrazolium ring of the soluble dye 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide ("MTT") to differentiate live cells from dead cells. Media for adherent cells is washed before MTT assay. The MTT assay is based on the production of a dark blue formazan product by active dehydrogenase in the 15 mitochondria of live cells. The numbers of live cells (cell proliferation), or the mitochondria activity of live cells, can be measured by absorbance of visible light by the formazan at 595 nm. Example 1: D-Erythrose inhibits cancer cell growth. Example 1.1: MCF-7 (Human breast adenocarcinoma cell line) was cultivated with 20 different concentrations of D-erythrose in 1 g/L glucose DMEM media for 24 hours. Live and dead cells were counted with Trypan-Blue assay (Table 1.1). Table 1.1: Live and dead cell percentage with different D-erythrose concentration D-erythrose (mg/L) 10 50 100 200 300 400 live dead live dead live dead live Idead live dead live dead MCF-7 98.1 1.999.4 0.699.4 0.6100 0.0.0 100.0 0.055.4 44.6 24 WO 2010/043029 PCT/CA2009/001440 Example 1.2: Mouse Lung Carcinoma (LL2) was cultivated with different concentrations of D-erythrose and glucose for 48 hours in DMEM media. Live cell percentage was counted with Trypan-Blue assay (Table 1.2a), 0 mg/L D-erythrose was control at 100%. Lower concentration had no effect in cell death; cell 5 proliferation was inhibited with increasing concentration of D-erythrose. Cell proliferation based on mitochondria activity was measured by MTT assay (Table 1.2b). Cell proliferation decreased with increasing D-erythrose. Table 1.2a: Live cell comparison of LL2 with different D-erythrose and glucose concentration for 48 hr D-erythrose(mg/L) 0 10 25 50 75 100 150 250 500 Media\ Live Cell Comparison 1 g/L glucose 100% 100% 100% 100% 100% 100% 95% 85% 30% 2g/L glucose 100% 100% 100% 100% 100% 100% 95% 85% 30% 4g/L glucose 100% 100% 100% 100% 100% 100% 95% 85% 30% 10 Table 1.2b: Cell proliferation of LL2 with different D-erythrose and glucose concentration for 48 hr

D

erythrose (mg/L) 0 10 25 50 75 100 150 250 500 1g/L 1.51 1.77 1.83 1.80 1.87 1.76 1.77 1.61 1.13 glucose (±0.16) (±0.13) (±0.02) (±0.28) (±0.16) (*0.41) (±0.19) (±0.15) (±0.31) 2g/L 1.58 1.50 1.48 1.62 1.33 1.62 1.56 1.36 0.74 glucose (±0.58) (±0.09) (±0.13) (±0.33) (±0.37) (0.36) (±0.39) (±0.38) (±0.25) 4g/L 1.59 1.49 1.52 1.48 1.42 1.43 1.49 1.51 0.97 glucose (20.18) (±0.07) (±0.03) (±0.06) (±0.12) (*0.22) (±0.08) (±0.13) ( 0.09) Example 1.3: Human colorectal cancer cell line (SW480) was cultivated with different concentrations of D-erythrose in 1 g/L glucose DMEM media for 48 hours and mouse colon cancer cell line (CT26) was cultivated with different 15 concentrations of D-erythrose in 1 g/L glucose RPM1640 media for 48 hours. Cell proliferation based on mitochondria activity was measured by MTT assay (Table 1.3). 25 WO 2010/043029 PCT/CA2009/001440 Table 1.3: Cell proliferation of SW480 and CT26 with D-erythrose in 1 g/L glucose media for 48 hr

D

erythrose (mg/L) 0 10 25 50 75 100 150 250 500 SW480 0.65 0.68 0.67 0.7 0.71 0.66 0.68 0.54 0.15 in DMEM (±0.02) (±0.05) (±0.07) (±0.07) (±0.08) (±0.03) (±0.03) (±0.07) (±0.00) CT26 in RPMI 0.6 0.58 0.53 0.56 0.57 0.55 0.49 0.41 0.13 1640 (±0.01) (±0.03) (*0.14) (±0.01) (±0.02) (±0.04) (±0.05) (±0.00) (±0.03) Example 1.4: Mouse colon cancer cell line (CT26) was cultivated with different concentrations of D-erythrose in 1 g/L glucose DMEM media for 24 or 48 hours. 5 Cell proliferation based on mitochondria activity was measured by MTT assay (Table 1.4). Table 1.4: Cell proliferation of CT26 with D-erythrose in 1 g/L DMEM media for 24 or 48 hr D-erythrose (mg/L) 0 25 50 75 100 150 250 500 0.76 0.78 0.76 0.73 0.77 0.68 0.11 24hr (±0.02) (±0.02) (+0.04) (±0.02) (±0.02) (±0.03) (±0.01) 0.8 0.71 0.64 0.68 0.66 0.59 0.54 0.16 48hr (±0.00) (±0.11) (*0.04) (±0.04) (±0.05) (±0.02) (±0.00) (±0.02) Example 1.5: With different concentrations of glucose and D-erythrose in DMEM 10 tissue culture media, three cells lines in vitro were tested: U87MG, BT474 and Panc-1. After 96 hours incubation, no massive adhering cell population could be observed for all cancer cell lines under microscopy. Cell viability was determined with Trypan-Blue assay (Table 1.5). Table 1.5: Viability after culture with different concentration of glucose and D 15 erythrose 26 WO 2010/043029 PCT/CA2009/001440 Cancer Growth condition Cell/Well at Cell/Well at Viability Live cell Cell Line the start of the end of (%) number culture culture change (%) S4.5 g/L glucose 100,000 780,000 92 617.6 5 1.0 g/L glucose + 100,000 45,000 33.3 -85.02 a- 3.5 g/L D-erythrose 4.5 g/L D-erythrose 100,000 20,000 66.7 -86.66 4.5 g/L glucose 70,000 435,000 100 521.43 t 1.0 g/L glucose + 0 0 -100 3 3.5 g/L D-erythrose 70,000 4.5 g/L D-erythrose 70,000 0 0 -100 4.5 g/L glucose 80,000 85,000 100 6.25 1.0 g/L glucose + 0 0 -100 3.5 g/L D-erythrose 80,000 4.5 g/L D-erythrose 80,000 0 0 -100 Example 2: Zinc enhance D-Erythrose's ability of inhibiting cancer cell growth MCF-7 (Human breast adenocarcinoma cell line) was cultivated with different concentrations of ZnC 2 in 1 g/L glucose and 400 mg/L D-erythrose DMEM media for 24 hours (Table 2.1). HEL (Human Erythroleukemia) was cultivated with 5 different concentrations of ZnC 2 and D-erythrose in 1 g/L glucose DMEM media for 24 hours, live cell comparison with OpM added ZnC 2 as 100% (Table 2.2). Live and dead cells were counted with Trypan-Blue assay. Table 2.1: Live and dead cell percentage of MCF-7 with different concentration of ZnCl 2 Added ZnCl 2 (pM) 0 3 5 10 20 40 live dead live dead live dead live dead live dead liveldead MCF-7 55.4 44.656.8 43.2 28. 72. 19.6 80.424. 75.3 5.2 94.8 10 Table 2.2: Live cell comparison of HEL with different concentration of ZnC 2 and D-erythrose D-erythrose (mg/L) \ Added ZnCl 2 (PM) 0 3 5 10 20 40 400 100%75%81%82%52% 48% 300 100%189%96%99%78% 75% 27 WO 2010/043029 PCT/CA2009/001440 Example 3: D-Erythrose enhance cell viability. Mouse Lung Carcinoma (LL2) and mouse colon cancer cell line (CT26) were cultivated with different concentrations of D-erythrose in low glucose (0.5g/L) DMEM media for 48 hours. Live cell percentage of LL2 was counted with Trypan 5 Blue assay (Table 3.1), 0 mg/L D-erythrose was control as 100%; data of treatment was comparable result of same glucose concentration. Cell proliferation based on mitochondria activity was measured by MTT assay (Table 3.2). In low glucose (0.5 g/L) media, D-erythrose increased cell viability. Table 3.1: Live cell comparison of LL2 for 48 hr with D-erythrose in 0.5g/L glucose 10 DMEM

D

erythrose(mg/L) 0 10 25 50 75 100 150 250 500 LL2 100%120%120%120%120%120%120%120%120% Table 3.2: Cell proliferation of LL2 and CT26 for 48 hr with D-erythrose in 0.5g/L glucose DMEM D-erythrose (mg/L) 10 25 50 100 150 250 500 0.27 0.35 0.36 0.37 0.43 0.42 0.52 0.4 LL2 (±0.03) (±0.06) (±0.01) (±0.01) (±0.01) (±0.02) (±0.03) (±0.03) 0.12 0.17 0.17 0.17 0.15 0.16 0.2 0.15 CT26 (±0.02) (±0.03) (10.03) (±0.10) (10.01) (±0.03) (±0.02) (±0.00) Example 4: Zinc enhance D-Erythrose's ability of increasing cell viability MCF-7 (Human breast adenocarcinoma cell line) was cultivated with different 15 concentrations of D-erythrose and ZnCl 2 in 1 g/L glucose DMEM media for 24 hours. Live cell percentage was counted with Trypan-Blue assay (Table 4.1 and Table 4.2). Zinc enhances D-erythrose's ability of increasing cell viability. Table 4.1: Live cell percentage of MCF-7 with different concentration of D erythrose and ZnCl 2 compare to Omg/L D-erythrose 28 WO 2010/043029 PCT/CA2009/001440 D-erythrose (mg/L) \ Added ZnCl2 (PM) 5 10 20 40 100 106%128%137%110% 50 116%139%131%121% 10 131%142%107%131% 0 100%100%100%100% Table 4.2: Live cell percentage of MCF-7 with different concentration of D erythrose and ZnC 2 compare to 0 or 1 pM Added ZnCI2 D-erythrose (mg/L) \ Added ZnCl2 (PM) 0orl 5 10 20 40 100 100%117%124%141%115% 50 100%111%117%117%110% 10 100%1126%119% 119% Example 5: L-Erythrulose inhibits cancer cell growth. Mouse Lung Carcinoma (LL2) was cultivated with different concentrations of D 5 erythrulose for 24 hours in 1 g/L glucose DMEM media. Cell proliferation based on mitochondria activity was measured by MTT assay (Table 5). L-erythrulose has anti-cancer effect. Table 5: Cell proliferation of LL2 for 24 hr with L-erythrulose in 1 g/L glucose DMEM L-erythrulose (mg/L) 0 1000 2000 5000 10000 LL2 0.83±0.01 0.64±0.02 0.54±0.02 0.53±0.04 0.34±0.05 10 Example 6: L-Erythrulose enhance cell viability Mouse Lung Carcinoma (LL2) was cultivated with different concentrations of D erythrulose in low glucose (0.5g/L) DMEM media for 24 hr. Cell proliferation based on mitochondria activity was measured by MTT assay (Table 6). Table 6: Cell proliferation of LL2 for 24 hr with L-erythrulose in 0.5g/L glucose 15 DMEM 29 WO 2010/043029 PCT/CA2009/001440 L-erythrulose & 1000 & 2000 & 5000 & Glucose (mg/L) 0 & 500 500 500 500 0 & 1000 LL2 0.56±0.030.820.030.86±0.170.82±0.180.73±0.04 Example 7: D-threose inhibit cancer cell growth. Mouse Lung Carcinoma (LL2) was cultivated with different concentrations of D threose for 48 hours in 1g/L glucose DMEM media. Live cell percentage was counted with Trypan-Blue assay (Table 7.1), 0 mg/L D-threose was control as 5 100%. Cell proliferation based on mitochondria activity was measured by MTT assay (Table 7.2). Cell proliferation decreased with increasing D-threose in 1g/L glucose DMEM media. Table 7.1: Live cell comparison of LL2 for 48 hr with different D-threose concentration in 1 g/L glucose D-threose concentration (mg/L) 0 100 150 200 250 300 350 400 450 500 LL2 100%1100% 100%195%195%190%190%185%180%175% 10 Table 7.2: Cell proliferation of LL2 for 48 hr with different D-threose concentration in 1g/L glucose D-threose concentration 0 500 1000 1500 2000 2500 3000 (mg/L) LL2 1.52 1.04 0.47 0.45 0.45 0.34 0.28 (±0.04) (±0.07) (±0.06) (±0.02) (±0.01) (±0.03) (±0.02) Example 8: D-Erythrose inhibit tumour growth in mice. Mice with tumours grown from CT26 cell line under mice's skin were treated with an injection of 8mg D-erythrose beside the tumour per mouse daily. Comparing to 15 control (treated with PBS), tumour growth rate was decreased by 19.46% in two days by the treatment of D-erythrose. There was no significant difference (<1%) in weight changes between the treatment group and the control group. 30 WO 2010/043029 PCT/CA2009/001440 Another two groups of mice with tumour were treated with 1) an injection of 20mg D-erythrose beside the tumour per mouse daily; 2) two injections of 20mg D erythrose beside the tumour per mouse daily. Tumour growth rate reduced 90% for group 1. (Table 8). For group 2, the average 5 tumour size shrank about 50% of the original size on day 4 (six mice in the group, except of an extreme one, the average tumour size for other 5 mice shrank 95%.) Table 8: Tumour size (mm 3 ) and tumour growth rate with once a day or twice a day 20 mg D-erythrose injection. Da 1 Dav 4 Chanae % Control 7.38±3.45 47.92±10.74 549.66% Once daily 7.94±1.71 12.31±16.80 55.01% Twice daily 948±3.11 4.26±9.44 -55.04% Examples and embodiments not limiting: 10 The embodiments and examples presented herein are illustrative of the general nature of the subject matter claimed and are not limiting. It will be understood by those skilled in the art how these embodiments can be readily modified and/or adapted and/or combined for various applications and in various ways without departing from the spirit and scope of the subject matter disclosed claimed. The 15 claims hereof are to be understood to include without limitation all alternative embodiments and equivalents of the subject matter hereof. Phrases, words and terms employed herein are illustrative and are not limiting. Where permissible by law, all references cited herein are incorporated by reference in their entirety. It will be appreciated that any aspects of the different embodiments disclosed herein 20 may be combined in a range of possible alternative embodiments, and alternative combinations of features, all of which varied combinations of features are to be understood to form a part of the subject matter claimed. 31

Claims

1. A method for inhibiting the growth of a cancer cell comprising directly or indirectly exposing said cancer cell to a pharmaceutically effective concentration 5 of tetrose.

2. The method according to claim 1 wherein the tetrose has a structural formula selected from the group consisting of: C 4 H 8 O4 H 0 H 0 C CH2OH C I I I H-C-OH C=0 HO-C-H H-C-OH H-C-OH H-C-OH I I I CH2OH CH2OH CH2OH C 4 H 6 0 4 H 0 H 0 H O H 0 H 0 C C CH-C -OH C=0 0=C H-C-OH HO-C-H H-C-OH H-C-OH H-C-OH C=0 C=0 C I I I IH-C O CH2OH HH CH2OH CH2OH CH2OH H 0 H 0 C H 0 H 0 H 0 H 0 HO-C-H C C C NU L;- II II H-C-OH C-OH HO-C H-C-OH HO-C-H I || ||| C C-OH C-OH C-OH C-OH 0 H CH2OH CH2OH CHOH CHOH 32 WO 2010/043029 PCT/CA2009/001440 C 4 HS0 3 H 0 H O H 0 H O H 0 C C C C C I I I I I H-C-H H-C-H H-C-OH HO-C -H H-C-OH I I I II H-C-OH H-C-OH H-C-H H-C-H H-C-OH I I I I CH2OH CH2OH CH2OH CH2OH CH3 H 0 C HO -C - H H -C - OH CH3 C 4 H 6 0 3 H 0 H 0 H 0 H o0 C C C C I I I I C=0 O=C H-C-H H-C-H H-C-H H-C-H C=O C=O I I I I CH2OH CH2OH CH2OH CH2OH H 0 H O H 0 H 0 C C C C H-C-H H-C-H H-C-OH HO-C-H I I I I H-C-OH H-C-OH H-C -H H-C-H C C C C H 0 0 H H 0 0 H H 0c 0 O H 0 H 0 C C C C C-OH HO-C C-H H-C C-H C-H C-OH C-OH I I I I CH2OH CH2OH CH2OH CH2OH 33 WO 2010/043029 PCT/CA2009/001440 C 4 H 4 0 4 H 0 H O H 0 H 0 H 0 C C C 4pN- z I I I C C C=O 0 =0 H-C-OH I I I I I C=0 0=0 H-C-OH H-C-OH C=0 C=0 C=0 C C C I I / % /% / % CH2OH CH2OH H 0 H 0 H 0 H 0 C HO - C - H H 0 C 4 H 4 0 3 H 0 H 0 H 0 H 0 H 0 C C C "NI I I C C C=0 0 =0 H-C-H 0=0 O=C H-C-H H-C -H C=0 0=0 0=0 0 C C CH3 CH3 H 0 H 0 H 0 H 0 C H-C -H C=0 C / % H 0 34 WO 2010/043029 PCT/CA2009/001440 C 4 H 6 0 2 H 0 "\ //, H 0 H 0 H H 0 C C C C C H-C-H I I I I C=0 0=0 H-C-H H-C -H H-C-H H-C-H H-C-H =0 C=0 C CH3 CH3 CH3 CH3 H 0 H 0 C H-C -H H-C -H C 0 H C 4 H 8 0 2 H 0 H O H 0 H O H 0 H 0 C C C C C C H-C-OH HO-C-H H-C H- H-C-H H-C-H H-C-H I I I I I I H-C-H H-C-H H-C-OH H-C-OH H-C-H H-C-H I I I I I CH3 CH3 CH3 CH3 CH2OH CH2OH and any pharmaceutically effective derivatives thereof.

3. The method according to claim 2 wherein the derivative is a conjugated, substituted, ionised, salt, isomeric, acid, base, aldehyde, ketone, alcohol, amine, 5 amide, thiol, ring or linear form.

4. The method according to claim 1 wherein the tetrose is selected from the group consisting of erythrose, threose and erythrulose.

5. The method according to claim 1 wherein said indirect exposing comprises exposing said cancer cell to a prodrug metabolisable to release tetrose. 35 WO 2010/043029 PCT/CA2009/001440

6. The method according to claim 1 wherein said cancer cell is exposed to a concentration of greater than about 100 mg/litre of tetrose.

7. The method according to claim 1 wherein said cancer cell is exposed to a glucose concentration of greater than about 500 mg/litre before or simultaneous 5 with said exposure to tetrose.

8. The method according to claim 1 wherein said cancer is selected from the group consisting of carcinoma, sarcoma, adenoma, leukemia, lymphomas and myeloma

9. The method according to claim 1 wherein said exposure occurs in combination 10 with exposing said cell to a modulator of carbonic anhydrase activity.

10. The method according to claim 9 wherein said modulator comprises a Zinc salt.

11. A method for improving the viability of a cell, said method comprising directly or indirectly exposing said cell to a therapeutically effective amount of tetrose. 15

12. The method according to claim 11 wherein the tetrose has a structural formula selected from the group consisting of: C 4 Ha0 4 H 0 H 0 C CH2OH C H-C-OH C=0 HO-C-H I I I H-C-OH H-C-OH H-C-OH I I I CH2OH CH2OH CH2OH 36 WO 2010/043029 PCT/CA2009/001440 C 4 H 6 0 4 H 0 H 0 H O H 0 H 0 C C C C C H-C-OH I I I I C=O O=C H-C-OH HO-C-H H-C-OH H-C-OH H-C-OH C=O C=O C CH2OH CH2OH CH2OH CH2OH H 0 H 0 C H 0 H 0 H H o0 HO-C-H CCCC H O - HII I I H-C-O C-OH HO-C H i- C- OH HO-C C C-OH C-OH C -OH C-OH I | Il || 0 H CH2OH CH2OH CHOH CHOH C 4 H 8 0 3 H 0 H O H 0 H O H 0 C C C C C el I 4p 0 H-C-H H-C-H H-C-OH HO-C-H H-C-OH I I I I I H-C-OH H-C-OH H-C-H H-C-H H-C-OH I | I | CH2OH CH2OH CH2OH CH2OH CH3 H 0 C HO - C - H H - C - OH CH3 C 4 H 6 0 3 H 0 H 0 H 0 H 0 C C C C I I II C-O O=C H-C-H H-C-H H-C-H H-C-H C=O C=O I I CH2OH CH2OH CH2OH CH2OH 37 WO 2010/043029 PCT/CA2009/001440 H 0 H OH H 0 C C C C I I I I H-C-H H-C-H H-C-H HO-C-H I I I I H -Cu-OH H -CU-OH H-C -Ht H- C- H I I I I C C C C H 0 0 H H 0 0 H H 0c 0 O H 0 H 0 C C C C C-OH HO-C C-H H-C C-H C-H C -OH C -OH I I I | CH2OH CH2OH CH2OH CH2OH C 4 H 4 0 4 H 0p 0 O H 0 H 0 H 0 C C C Nl 0 l 4PI I I C C C=O 0 =C H-C-OH II I I I C=0 O=C H-C-OH H-C-OH C=0 I I z Ik C=0 C=O C C C CH2OH CH2OH H 0 H 0 H 0 H 0 C HO -C - H C=O C H 0 C 4 H 4 0 3 H 0c 0 O H 0 H 0 H 0 C C C C C C=0 0 =C H-C-H C=O O=C H-C-H H-C-H C=O C=O C=O C C C CH3 CH3 H 0 H 0 H 0 38 WO 2010/043029 PCT/CA2009/001440 H 0 C H-C -H C=0 C H 0 C 4 H 6 0 2 H 0 H 0 H 0 H 0 H O C C C C C H-C-H C=0 0=C H-C-H H-C -H H-C-H I I I I I H-C-H H-C-H C=O C=O C CH3 CH3 CH3 CH3 H 0 H 0 C H-C -H H-C -H C O H C 4 H 8 0 2 H 0C 0 O H 01 0 O H 0 H 0 C C C C C C S1 1 1 1 1 H-C-OH HO-C-H H-C-H H-C-H H-C-H H-C-H I I I I I I H-C-H H-C-H H-C-OH H-C-OH H-C-H H-C-H I I I I I I CH3 CH3 CH3 CH3 CH2OH CH2OH and any pharmaceutically effective derivatives thereof.

13. The method according to claim 12 wherein the derivative is a conjugated, substituted, ionised, salt, isomeric, acid, base, aldehyde, ketone, alcohol, amine, amide, thiol, ring or linear form. 39 WO 2010/043029 PCT/CA2009/001440

14. The method according to claim 11 wherein said exposure occurs in combination with exposing said cell to a modulator of carbonic anhydrase activity.

15. The method according to claim 11 wherein said cell is under conditions of limited energy supply. 5

16. The method according to claim 11 wherein said cell has a mitochondrial disorder.

17. The method according to claim 11 wherein the tetrose is selected from the group consisting of erythrose, threose and erythrulose.

18. The method according to claim 11 wherein said indirect exposing comprises 10 exposing said cell to a prodrug metabolisable to release tetrose.

19. The method according to claim 11 comprising exposing said cells to a concentration of between about 1 mg/litre and about 200 mg/litre of said tetrose.

20. The method according to claim 16 wherein said mitochondrial disorder is associated with a disorder selected from the group consisting of 15 neurodegenerative disease, Alzheimer's disease, Parkinson's disease, Huntington's disease, cardiovascular disease, stroke, obesity, diabetes, multiple sclerosis, systemic lupus erythematosis, rheumatoid arthritis, schizophrenia, bipolar disorder, depression, ataxia, autism, epilepsy, migraine, Batten disease, Lactic acidemia, Leber's disease, mitochondrial cardiomyopathy and myopathy, 20 paraplegin, NASH, and Wilson's disease.

21. A method of treating a mitochondrial disorder in a subject having such disorder, said method comprising directly or indirectly administering to the subject a pharmaceutically effective dose of tetrose.

22. The method according to claim 21 wherein the tetrose has a structural formula 25 selected from the group consisting of: 40 WO 2010/043029 PCT/CA2009/001440 C 4 H 8 O4 H 0 H 0 C CH2OH C H-C-OH C=O HO-C-H I I H-C-OH H-C-OH H-C-OH I II CH2OH CH2OH CH2OH C 4 H 6 0 4 H 0 H 0 H O H 0 H 0 C H-C-OH C=0 O=C H-C-OH HO-C-H H-C-OH I I I I H-C-OH H-C-OH C=O C=O C I I I |I CH2OH CH2OH CH2OH CH2OH H 0 H 0 C H 0 H 0 H O H 0 HO-C-H C C C C C HII II H-C-OH C-OH HO-C H-C-OH HO-C-H I || || II C C-OH C-OH C-OH C-OH 0 H CH2OH CH2OH CHOH CHOH C 4 H 8 0 3 H 0 H O0H H OH 0 C C C C C H-C-H H-C-H H-C-OH HO-C -H H-C-OH I I I I I H-C-OH H-C -OH H-C-H H-C -H H-C-OH CH2OH CH2OH CH2OH CH2OH CH3 H 0 C HO- C - H H-C -OH CH3 41 WO 2010/043029 PCT/CA2009/001440 C 4 H 6 0 3 H 0 H O H 0 H 0 C C C C C=O O=C H-C-H H-C-H H-C-H H-C-H C=O C=0 I I I I CH2OH CH2OH CH2OH CH2OH H 0 H O H 0 H 0 C C C C I I I I H-C-H H-C-H H-C -OH HO-C -H H-C -OH H-C-OH H-C -H H-C-H C C C C H 0 0 H H 0 0 H H 0 H O H 0 H 0 C C C C Is I z% I II C-OH HO-C C-H H-C C-H C -H C-OH C-OH I I I | CH2OH CH2OH CH2OH CH2OH C 4 H 4 0 4 H 0 H OH H 0 H O C C C I C C C=O 0 =C H-C-OH C= 0=C H-C-OH H-C-OH C=0 II I C=O C=O C C C 10,INI7%Z% 7 CH2OH CH2OH H 0 H 0 H 0 H 0 C HO - C - H C=0 C H 0 42 WO 2010/043029 PCT/CA2009/001440 C 4 H 4 0 3 H 0 H 0 H 0 H 0 H 0 C C C II/ 11 o I I I C C C=0 0 =C H-C-H I I I I I C=O C=0 C C C CH3 CH3 H 0 H 0 H 0 H 0 C H-C -H C=0 C H 0 C 4 H 6 0 2 H 0 H 0 H 0 H 0 H 0 C C C C C H-C-H 0=0 O=C H-C-H H-C -H H-C-H H-C-H H-C-H C=0 C=0 C CH3 CH3 CH3 CH3 H 0 H 0 C H-C -H H-C -H C 0 H 43 WO 2010/043029 PCT/CA2009/001440 C 4 H 8 0 2 H 0 H O H 0 H O H 0 H 0 C C C C C C I I I III H-C-OH HO-C-H H-C-H H-C-H H-C-H H-C-H I I I I |I H-C-H H-C-H H-C-OH H-C-OH H-C-H H-C-H I I | I CH3 CH3 CH3 CH3 CH2OH CH2OH and any pharmaceutically effective derivatives thereof.

23. The method according to claim 22 wherein the derivative is a conjugated, substituted, ionised, salt, isomeric, acid, base, aldehyde, ketone, alcohol, amine, 5 amide, thiol, ring or linear form.

24. The method according to claim 21 wherein the tetrose is selected from the group consisting of erythrose, threose and erythrulose.

25. The method according to claim 21 wherein said exposure occurs in combination with exposing said cell to a modulator of carbonic anhydrase activity. 10

26. A composition comprising: a direct or indirect source of tetrose in an amount effective to inhibit the growth of a cancer cell; and a pharmaceutically acceptable carrier or diluent.

27. A composition comprising: 15 a direct or indirect source of tetrose in an amount effective to increase the viability of a cell having a mitochondrial disorder; and a pharmaceutically acceptable carrier or diluent

28. The use of an effective dose of a direct or indirect source of tetrose to achieve an effect selected from the group consisting of: 44 WO 2010/043029 PCT/CA2009/001440 inhibiting the growth of a cancer cell; increasing the viability of a cell under low energy conditions; and increasing the viability of a cell having a mitochondrial disorder.

29. The use according to claim 28 wherein the tetrose has a structural formula 5 selected from the group consisting of: C 4 H 8 O4 H 0 H 0 C CH2OH C H-C-OH C=0 HO-C-H I I | H-C-OH H-C-OH H-C-OH CH2OH CH2OH CH2OH C 4 H 6 0 4 H 0 H 0 H O H 0 H 0 C C C C C H-C -OH I I III C=0 0=0 H-C-OH HO-C-H H-C-OH I I I H-C-OH H-C-OH C=0 C=0 C I I I .0 k CH2OH CH2OH CH2OH CH2OH H 0 H 0 C H 0 H 0 H 0 H O HO-C-H C C C C HO -C -HII II H-C-OH C -OH HO-C H-C -OH HO -C -H C C-OH C-OH C-OH C-OH 0 H CH2OH CH2OH CHOH CHOH 45 WO 2010/043029 PCT/CA2009/001440 C 4 HS0 3 H 0 H O H 0 H O H 0 C C C C C I I I | | H-C-H H-C-H H-C-OH HO-C -H H-C-OH I I I I I H-C-OH H-C-OH H-C-H H-C-H H-C-OH II I |I CH2OH CH2OH CH2OH CH2OH CH3 H 0 C HO - C - H H -C -OH |CH3 C 4 H 6 0 3 H 0 H OH O H 0 C C C C C=O O=C H-C-H H-C-H H-C-H H-C-H C=O C=O I I I I CH2OHii CH2OH CH2OH CH2OH H 0 H O H 0 H 0 C C C C /, N.I I- N Ilo H-C -H H-C-H H-C -OH HO-C-H I I I I H-C -OH H-C-OH H-C -H H-C-H I I I I C C C C H 0 0 H H 0 0 H H 0 H O H 0 H 0 C C C C I I I I C-OH HO-C C-H H-C || Il Il || I I I I CH2OH CH2OH CH2OH CH2OH 46 WO 2010/043029 PCT/CA2009/001440 C 4 H 4 0 4 H 0c 0 O H 0 H 0 H 0 C C C C C C=0 0 =C H-C-OH C=O O=C H-C-OH H-C-OH C=0 C=0 C=0 C C C I Ix CH2OH CH2OH H 0 H 0 H 0 H 0 C HO - C -H C=0 C H 0 C 4 H 4 0 3 H 0 H O H 0 H 0 H O C C C C C C=O 0 =C H-C-H C=0 O=C H-C-H H-C -H C=O I II I | C=0 C=0 C C C IN CH3 CH3 H 0 H 0 H 0 H 0 C H-C -H C=0 C H 0 C 4 H40 2 47 WO 2010/043029 PCT/CA2009/001440 H 0 H 0 H 0 H 0 H 0 C C C C c H-C-H I I I I I 0=0 O=C H-C-H H-C -H H-C-H H-C-H H-C-H C=0 C=0 C CH3 CH3 CH3 CH3 H 0 H 0 C H-C -H H-C -H C O H 48 WO 2010/043029 PCT/CA2009/001440 C 4 HaO2 H 0 H O H 0 H O H 0 H 0 C C C C C C H-C-OH HO-C-H H-C-H H-C-H H-C-H H-C-H I I I I I I H-C-H H-C-H H-C-OH H-C-OH H-C-H H-C-H II I I I I CH3 CH3 CH3 CH3 CH2OH CH2OH and any pharmaceutically effective derivatives thereof.

30. The method according to claim 28 wherein the derivative is a conjugated, substituted, ionised, salt, isomeric, acid, base, aldehyde, ketone, alcohol, amine, 5 amide, thiol, ring or linear form.

31. The method according to claim 28 wherein the tetrose is selected from the group consisting of erythrose, threose and erythrulose.

32. The use of tetrose or a prodrug of tetrose to manufacture a dietary supplement. 10

33. A composition comprising a prodrug metabolisable to yield a pharmaceutically effective amount of tetrose to: inhibit the growth of a cancer cell; increase the viability of a cell under low energy conditions; and increase the viability of a cell having a mitochondrial disorder. 15

34. The composition according to claim 33 wherein the tetrose has a structural formula selected from the group consisting of: 49 WO 2010/043029 PCT/CA2009/001440 C 4 HO4 H 0 H 0 C CH2OH C I I I H-C-OH C=0 HO-C-H I II H-C-OH H-C-OH H-C-OH I II CH2OH CH2OH CH2OH C 4 H 6 0 4 H 0 H 0 H O H H 0 C C C C C H-C -OH II I I H -C -O C=O O=C H-C-OH HO-C-H H-C-OH I I I H C O H-C-OH H-C-OH C=0 C=O C i I I I Ile CH2OH CH2OH CH2OH CH2OH H 0 H 0 C H 0 H 0 H 0 H 0 HO-C-H CC C C NO -C -HII I H-C-OH C -OH HO-C H-C -OH HO-C -H 11 || I C C-OH C-OH C-OH C-OH I I || || O H CH2OH CH2OH CHOH CHOH C 4 H 8 O 3 H 0 H O H 0 H O H 0 C C C C C I I I I I H-C-H H-C -H H-C-OH HO-C -H H-C-OH SI I I H-C-OH H-C-OH H-C-H H-C -H H-C-OH CH2OH CH2OH CH2OH CH2OH CH3 H 0 C HO - C - H H - C - OH CH3 50 WO 2010/043029 PCT/CA2009/001440 C 4 H 6 0 3 H 0 H 0 H 0 H 0 C C C C C=0 0=C H-C-H H-C-H H-C-H H-C-H C=0 C=0 CH2OH CH2OH CH2OH CH2OH H 0 H O H 0 H 0 C C C C I I I I H-C -H H-C-H H-C-OH HO-C-H I I II H-C -OH H-C- H-C-H H-C-H I I I I C C C C H 0 0 H H 0 0 H H 0 H O H 0 H 0 C C C C II I I C-OH HO-C C-H H-C C-H C-H C-OH C-OH I I CH2OH CH2OH CH2OH CH2OH C 4 H 4 0 4 H 0 H O H 0 H 0 H 0 C C C I II C C C=0 0 =0 H-C-OH Nlo I I I C=0 0=C H-C-OH H-C-OH C=0 I II I| C=0 0=0 C C CH2OH CH2OH H 0 H 0 H 0 H 0 C HO - C - H C=0 C H 0 51 WO 2010/043029 PCT/CA2009/001440 C 4 H 4 0 3 H 0 H O H 0 H 0 H 0 C C C IN I , C C 0=0 0 =C H-C-H C=O O=C H-C-H H-C -H C=0 C=0 0=0 C C C C =0 CH3 CH3 H 0 H 0 H 0 H 0 C H-C -H C =0 C H 0 C 4 H 6 0 2 H 0 H 0 H 0 H 0 H 0 C C C C C H-C-H I I I I I C;=U O= H-C-H H -C -H H- C-H H-C-H H-C-H C=0 C=O C CH3 CH3 CH3 CH3 H 0 H 0 C H-C -H H-C -H C 0 H 52 WO 2010/043029 PCT/CA2009/001440 C 4 H0 2 H 0 H O H 0 H O H 0 H O C C C C C C H-C-OH HO-C-H H-C-H H-C-H H-C-H H-C-H II I I I H-C-H H-C-H H-C-OH H-C-OH H-C-H H-C-H I I I I I CH3 CH3 CH3 CH3 CH2OH CH2OH and any pharmaceutically effective derivatives thereof.

35. The composition according to claim 33 wherein the derivative is a conjugated, substituted, ionised, salt, isomeric, acid, base, aldehyde, ketone, alcohol, amine, 5 amide, thiol, ring or linear form.

36. The use of tetrose to manufacture a medicament for: a) inhibiting the growth of a cancer cell; or b) improving the viability of a cell exhibiting a mitochondrial disorder.

37. The use according to any one of claims 32, 33 and 36 wherein the tetrose is 10 selected from the group consisting of erythrose, threose and erythrulose. 53