METABOLIC PROFILES

1 . A method for normalising a disturbance in the metabolic profile of endogenous metabolites in a subject caused by rheumatoid arthritis (RA), the method comprising:

(i) measuring the levels of N endogenous metabolites in a biological sample obtained from the subject, wherein N is 11, in order to produce a metabolic profile of the N endogenous metabolites in that subject;

(ii) comparing the measured levels of the N endogenous metabolites with the corresponding levels of the endogenous metabolites in a biological sample obtained from a control;

wherein the N endogenous metabolites are selected from the group consisting of:

EM1

Phenylalanine

EM2

Tyrosine

EM3

Isoleucine

EM8

Glycine

EM9

Glutamine

EM10

Methionine

EM14

Lysine

EM15

Asparagine

EM16

Serine

EM17

Tryptophan

EM18

Threonine

wherein the disturbance in the metabolic profile is one wherein there is a decrease or increase in the level of each of the N measured endogenous metabolites in the biological sample obtained from the subject compared to the corresponding levels of endogenous metabolites in the biological sample obtained from the control, and wherein the disturbance in the metabolic profile is due to RA in the subject,

and if a disturbance in the metabolic profile is detected,

(iiia) prescribing or supplying to the subject or recommending treatment of the subject with an effective amount of N-(2-chloro-3,4-dimethoxybenzylideneamino) guanidine or an aminoguanidine, either as the free base or in salt form, for normalising the disturbed metabolic profile;

or

(iiib) administering to said subject an effective amount of N-(2-chloro-3,4-dimethoxybenzylideneamino)guanidine or an aminoguanidine, either as the free base or in salt form, for normalising the disturbed metabolic profile.

2 . A method for normalising a disturbance in the metabolic profile of endogenous metabolites in a subject caused by rheumatoid arthritis (RA), the method comprising:

(i) measuring the levels of N endogenous metabolites in a biological sample obtained from the subject, wherein N is 11, in order to produce a metabolic profile of the N endogenous metabolites in that subject;

(ii) comparing the measured levels of the N endogenous metabolites with the corresponding levels of the endogenous metabolites in a biological sample previously obtained from the subject;

wherein the N endogenous metabolites are selected from the group consisting of:

EM1

Phenylalanine

EM2

Tyrosine

EM3

Isoleucine

EM8

Glycine

EM9

Glutamine

EM10

Methionine

EM14

Lysine

EM15

Asparagine

EM16

Serine

EM17

Tryptophan

EM18

Threonine

wherein the disturbance in the metabolic profile is one wherein there is a decrease or increase in the level of each of the N measured endogenous metabolites in the biological sample obtained from the subject compared to the corresponding levels of endogenous metabolites in the biological sample previously obtained from the subject;

and wherein the disturbance in the metabolic profile is due to RA in the subject,

and if a disturbance in the metabolic profile is detected,

(iiia) prescribing or supplying to the subject or recommending treatment of the subject with an effective amount of N-(2-chloro-3,4-dimethoxybenzylideneamino) guanidine or an aminoguanidine, either as the free base or in salt form, for normalising the disturbed metabolic profile;

or

(iiib) administering to said subject an effective amount of N-(2-chloro-3,4-dimethoxybenzylideneamino)guanidine or an aminoguanidine, either as the free base or in salt form, for normalising the disturbed metabolic profile.

3 - 20 . (canceled)

21 . A method of preventing, delaying or reducing the onset of, or treating earlier than hitherto possible, a disturbed metabolic profile in a subject, which comprises:

a) detecting a disturbed metabolic profile caused by rheumatoid arthritis, by a method comprising:

(i) measuring the levels of N endogenous metabolites in a biological sample obtained from the subject, wherein N is 11, in order to produce a metabolic profile of the N endogenous metabolites in that subject;

(ii) comparing the measured levels of the N endogenous metabolites with the corresponding levels of the endogenous metabolites in a biological sample obtained from a control;

wherein the N endogenous metabolites are selected from the group consisting of:

EM1

Phenylalanine

EM2

Tyrosine

EM3

Isoleucine

EM8

Glycine

EM9

Glutamine

EM10

Methionine

EM14

Lysine

EM15

Asparagine

EM16

Serine

EM17

Tryptophan

EM18

Threonine

wherein the disturbance in the metabolic profile is one wherein there is a decrease or increase in the level of each of the N measured endogenous metabolites in the biological sample obtained from the subject compared to the corresponding levels of endogenous metabolites in the biological sample obtained from the control;

and wherein the disturbance in the metabolic profile is due to rheumatoid arthritis;

and

(b1) prescribing or supplying to the subject or recommending treatment of the subject with an amount of N-(2-chloro-3,4-dimethoxybenzylideneamino)guanidine or an aminoguanidine, either as the free base or in salt form, effective to prevent, delay, reduce or treat the onset of rheumatoid arthritis,

or

(b2) administering to said subject an amount of N-(2-chloro-3,4-dimethoxybenzylideneamino)guanidine or an aminoguanidine, either as the free base or in salt form, effective to prevent, delay, reduce or treat the onset of rheumatoid arthritis.

22 . A method of preventing, delaying or reducing the onset of, or treating earlier than hitherto possible, a disturbed metabolic profile in a subject, which comprises:

(a) detecting a disturbed metabolic profile caused by rheumatoid arthritis, by a method comprising:

(i) measuring the levels of N endogenous metabolites in a biological sample obtained from the subject, wherein N is 11, in order to produce a metabolic profile of the N endogenous metabolites in that subject;

(ii) comparing the measured levels of the N endogenous metabolites with the corresponding levels of the endogenous metabolites in a biological sample previously obtained from the subject;

wherein the N endogenous metabolites are selected from the group consisting of:

EM1

Phenylalanine

EM2

Tyrosine

EM3

Isoleucine

EM8

Glycine

EM9

Glutamine

EM10

Methionine

EM14

Lysine

EM15

Asparagine

EM16

Serine

EM17

Tryptophan

EM18

Threonine

wherein the disturbance in the metabolic profile is one wherein there is a decrease or increase in the level of each of the N measured endogenous metabolites in the biological sample obtained from the subject compared to the corresponding levels of endogenous metabolites in the biological sample previously obtained from the subject;

and wherein the disturbance in the metabolic profile is due to rheumatoid arthritis;

and

(b1) prescribing or supplying to the subject or recommending treatment of the subject with an amount of N-(2-chloro-3,4-dimethoxybenzylideneamino)guanidine or an aminoguanidine, either as the free base or in salt form, effective to prevent, delay, reduce or treat the onset of rheumatoid arthritis,

or

(b2) administering to said subject an amount of N-(2-chloro-3,4-dimethoxybenzylideneamino)guanidine or an aminoguanidine, either as the free base or in salt form, effective to prevent, delay, reduce or treat the onset of rheumatoid arthritis.

23 - 27 . (canceled)

28 . A method as claimed in claim 1 , wherein the biological sample is blood or synovial fluid.

29 . (canceled)

30 . A method as claimed in claim 1 , wherein the subject is a human.

31 - 32 . (canceled)

33 . A method as claimed in claim 1 , wherein one or more of the levels of the N endogenous metabolites are measured by spectroscopic techniques used in conjunction with a chemometric method, wherein the chemometric method is principal component analysis (PCA), partial least squares projections to latent structures (PLS), orthogonal PLS (OPLS), PLS discriminant analysis (PLS-DA) or orthogonal PLS-DA (OPLS-DA).

34 - 37 . (canceled)

38 . A method as claimed in claim 1 , wherein the increases/decreases in the levels of the endogenous metabolites (between the subject and the control samples or between the samples taken at different time intervals from the subject) are significant increases/decreases.

39 - 53 . (canceled)

54 . A method as claimed in claim 2 , wherein the biological sample is blood or synovial fluid.

55 . A method as claimed in claim 2 , wherein the subject is a human.

56 . A method as claimed in claim 2 , wherein one or more of the levels of the N endogenous metabolites are measured by spectroscopic techniques used in conjunction with a chemometric method, wherein the chemometric method is principal component analysis (PCA), partial least squares projections to latent structures (PLS), orthogonal PLS (OPLS), PLS discriminant analysis (PLS-DA) or orthogonal PLS-DA (OPLS-DA).

57 . A method as claimed in claim 2 , wherein the increases/decreases in the levels of the endogenous metabolites (between the subject and the control samples or between the samples taken at different time intervals from the subject) are significant increases/decreases.

58 . A method as claimed in claim 21 , wherein the biological sample is blood or synovial fluid.

59 . A method as claimed in claim 21 , wherein the subject is a human.

60 . A method as claimed in claim 21 , wherein one or more of the levels of the N endogenous metabolites are measured by spectroscopic techniques used in conjunction with a chemometric method, wherein the chemometric method is principal component analysis (PCA), partial least squares projections to latent structures (PLS), orthogonal PLS (OPLS), PLS discriminant analysis (PLS-DA) or orthogonal PLS-DA (OPLS-DA).

61 . A method as claimed in claim 21 , wherein the increases/decreases in the levels of the endogenous metabolites (between the subject and the control samples or between the samples taken at different time intervals from the subject) are significant increases/decreases.

62 . A method as claimed in claim 22 , wherein the biological sample is blood or synovial fluid.

63 . A method as claimed in claim 22 , wherein the subject is a human.

64 . A method as claimed in claim 22 , wherein one or more of the levels of the N endogenous metabolites are measured by spectroscopic techniques used in conjunction with a chemometric method, wherein the chemometric method is principal component analysis (PCA), partial least squares projections to latent structures (PLS), orthogonal PLS (OPLS), PLS discriminant analysis (PLS-DA) or orthogonal PLS-DA (OPLS-DA).

65 . A method as claimed in claim 22 , wherein the increases/decreases in the levels of the endogenous metabolites (between the subject and the control samples or between the samples taken at different time intervals from the subject) are significant increases/decreases.