Gene expression profiling for identification monitoring and treatment of multiple sclerosis

• US 20060115826A1
• Filed: 06/16/2005
• Published: 06/01/2006
• Est. Priority Date: 06/28/1999
• Status: Abandoned Application

• Current Assignee: Source Precision Medicine Inc.
• Original Assignee: Source Precision Medicine Inc.
• Inventors: Tryon, Victor V., Siconolfi, Lisa, Bankaitis-Davis, Danute, Trollinger, David B., Bevilacqua, Michael
• Application Number:
  US11/155,930
• Publication Number:
  US 20060115826A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 1/689 for bacteria
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/525 Tumor necrosis factor [TNF]
• CPC Class Codes: G01N 2800/285 Demyelinating diseases; Multipel sclerosis
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 25/10 Gene or protein expression profiling; Expression-ratio estimation or normalisation

Abstract

A method is provided in various embodiments for determining a profile data set for a subject with multiple sclerosis or inflammatory conditions related to multiple sclerosis based on a sample from the subject, wherein the sample provides a source of RNAs. The method includes using amplification for measuring the amount of RNA corresponding to at least 2 constituents from Table 1. The profile data set comprises the measure of each constituent, and amplification is performed under measurement conditions that are substantially repeatable.

Claims

1. A method for determining a profile data set for a subject with multiple sclerosis or inflammatory conditions related to multiple sclerosis based on a sample from the subject, the sample providing a source of RNAs, the method comprising:

using amplification for measuring the amount of RNA corresponding to at least 2 constituents from Table 1 and

arriving at a measure of each constituent,

wherein the profile data set comprises the measure of each constituent and wherein amplification is performed under measurement conditions that are substantially repeatable.

2. A method according to claim 1, wherein the subject has presumptive signs of a multiple sclerosis including at least one of:

altered sensory, motor, visual or proprioceptive system with at least one of numbness or weakness in one or more limbs, often occurring on one side of the body at a time or the lower half of the body, partial or complete loss of vision, frequently in one eye at a time and often with pain during eye movement, double vision or blurring of vision, tingling or pain in numb areas of the body, electric-shock sensations that occur with certain head movements, tremor, lack of coordination or unsteady gait, fatigue, dizziness, muscle stiffness or spasticity, slurred speech, paralysis, problems with bladder, bowel or sexual function, and mental changes such as forgetfulness or difficulties with concentration, relative to medical standards.

4. A method for determining a profile data set according to claim 1, wherein the measurement conditions that are substantially repeatable are within a degree of repeatability of better than five percent.

6. A method for determining a profile data set according to claim 1, wherein efficiencies of amplification for all constituents are substantially similar.

3. (canceled)

5. (canceled)

7-9. -9. (canceled)

10. A method of characterizing multiple sclerosis or inflammatory conditions related to multiple sclerosis in a subject, based on a sample from the subject, the sample providing a source of RNAs, the method comprising:

assessing a profile data set of a plurality of members, each member being a quantitative measure of the amount of a distinct RNA constituent in a panel of constituents selected so that measurement of the constituents enables characterization of the presumptive signs of a multiple sclerosis, wherein such measure for each constituent is obtained under measurement conditions that are substantially repeatable.

11. A method according to claim 10, wherein the subject has presumptive signs of a multiple sclerosis including at least one of:

altered sensory, motor, visual or proprioceptive system with at least one of numbness or weakness in one or more limbs, often occurring on one side of the body at a time or the lower half of the body, partial or complete loss of vision, frequently in one eye at a time and often with pain during eye movement, double vision or blurring of vision, tingling or pain in numb areas of the body, electric-shock sensations that occur with certain head movements, tremor, lack of coordination or unsteady gait, fatigue, dizziness, muscle stiffness or spasticity, slurred speech, paralysis, problems with bladder, bowel or sexual function, and mental changes such as forgetfulness or difficulties with concentration, relative to medical standards.

12. A method for characterizing multiple sclerosis or inflammatory conditions related to multiple sclerosis in a subject according to claim 10, wherein assessing further comprises:

comparing the profile data set to a baseline profile data set for the panel, wherein the baseline profile data set is related to the multiple sclerosis or inflammatory conditions related to multiple sclerosis to be characterized.

14. A method according to claim 10, wherein the multiple sclerosis or inflammatory conditions related to multiple sclerosis are with respect to a localized tissue of the subject and the sample is derived from a tissue of fluid of a type distinct from that of the localized tissue.

13. (cancelled)

15-16. -16. (canceled)

17. A method for evaluating multiple sclerosis or inflammatory conditions related to multiple sclerosis in a subject based on a first sample from the subject, the sample providing a source of RNAs, the method comprising:

deriving from the first sample a first profile data set, the profile data set including a plurality of members, each member being a quantitative measure of the amount of a distinct RNA constituent in a panel of constituents selected so that measurement of the constituents enables evaluation of the multiple sclerosis or inflammatory conditions related to multiple sclerosis wherein such measure for each constituent is obtained under measurement conditions that are substantially repeatable; and

producing a calibrated profile data set for the panel, wherein each member of the calibrated profile data set is a function of a corresponding member of the first profile data set and a corresponding member of a baseline profile data set for the panel, and wherein the baseline profile data set is related to the multiple sclerosis or inflammatory conditions related to multiple sclerosis to be evaluated,

the calibrated profile data set being a comparison between the first profile data set and the baseline profile data set, thereby providing evaluation of the multiple sclerosis or inflammatory conditions related to multiple sclerosis of the subject.

18. A method according to claim 17, wherein the subject has presumptive signs of a multiple sclerosis including at least one of:

altered sensory, motor, visual or proprioceptive system with at least one of numbness or weakness in one or more limbs, often occurring on one side of the body at a time or the lower half of the body, partial or complete loss of vision, frequently in one eye at a time and often with pain during eye movement, double vision or blurring of vision, tingling or pain in numb areas of the body, electric-shock sensations that occur with certain head movements, tremor, lack of coordination or unsteady gait, fatigue, dizziness, muscle stiffness or spasticity, slurred speech, paralysis, problems with bladder, bowel or sexual function, and mental changes such as forgetfulness or difficulties with concentration, relative to medical standards.

19. A method according to claim 17, wherein the baseline profile data set is derived from one or more other samples from the same subject taken under circumstances different from those of the first sample.

20. A method according to claim 19, wherein the circumstances are selected from the group consisting of (i) the time at which the first sample is taken, (ii) the site from which the first sample is taken, (iii) the biological condition of the subject when the first sample is taken.

25. A method according to claim 17, wherein the first sample is derived from blood and the baseline profile data set is derived from tissue or body fluid of the subject other than blood.

26. A method according to claim 17, wherein the first sample is derived from tissue or body fluid of the subject and the baseline profile data set is derived from blood.

27. A method according to claim 19, wherein the baseline profile data set is derived from one or more other samples from the same subject, taken when the subject is in a biological condition different from that in which the subject was at the time the first sample was taken, with respect to at least one of age, nutritional history, medical condition, clinical indicator, medication, physical activity, body mass, and environmental exposure.

28. A method according to claim 17, wherein the baseline profile data set is derived from one or more other samples from one or more different subjects.

29. A method according to claim 28, wherein the one or more different subjects have in common with the subject at least one of age group, gender, ethnicity, geographic location, nutritional history, medical condition, clinical indicator, medication, physical activity, body mass, and environmental exposure.

30. A method according to claim 29, wherein a clinical indicator has been used to assess multiple sclerosis or inflammatory conditions related to multiple sclerosis of the one or more different subjects, further comprising:

interpreting the calibrated profile data set in the context of at least one other clinical indicator.

31. A method according to claim 30, wherein the at least one other clinical indicator is selected from the group consisting of blood chemistry, urinalysis, X-ray or other radiological or metabolic imaging technique, other chemical assays, and physical findings.

39. A method according to claim 17, wherein the quantitative measure is determined by amplification, and the measurement conditions are such that efficiencies of amplification for all constituents differ by less than approximately 2 percent.

21-24. -24. (canceled)

32-38. -38. (canceled)

40-179. -179. (canceled)