Detection of HIV-1-associated neurocognitive disorders

Patent metadata

Field	Value
Publication number	US-10161925-B2
Application number	US-201515129353-A
Country	US
Kind code	B2
Filing date	Mar 24, 2015
Priority date	Mar 24, 2014
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

Provided is a method of detecting mild neurocognitive disturbance (MNCD) or HIV associated dementia (HAD) in a patient comprising detecting the level of acetyl spermine and/or acetyl spermidine from a cerebrospinal fluid test sample of the patient; and comparing the level of acetyl spermine and/or acetyl spermidine in the test sample to the level of the acetyl spermine and/or acetyl spermidine in a cerebrospinal fluid control sample or to a control value for lack of neurocognitive impairment, MNCD or HAD; wherein an elevated level of acetyl spermine and/or acetyl spermidine in the test sample as compared to the level in the control sample or a control value for lack of neurocognitive impairment, or a level of acetyl spermine and/or acetyl spermidine that is similar to that of a control value for MNCD or HAD, indicates that the patient suffers from MNCD or HAD. Also provided are methods for measuring the progression of an HIV-1-associated neurocognitive disorder, as well as methods for staging such a disorder.

First claim

What is claimed is:

1. A method of detecting and treating mild neurocognitive disturbance (MNCD) or HIV associated dementia (HAD) in a patient comprising:
(a) detecting the level of acetyl spermine and/or acetyl spermidine from a biological test sample of said patient; and
(b) (i) comparing said level of acetyl spermine and/or acetyl spermidine in said test sample to the level of acetyl spermine and/or acetyl spermidine in a biological control sample; wherein an elevated level of acetyl spermine and/or acetyl spermidine in said test sample as compared to the level in said control sample indicates that the patient suffers from mild neurocognitive disturbance or HIV associated dementia; or
(ii) comparing said level of acetyl spermine and/or acetyl spermidine in said test sample to a standard value or standard value range for mild neurocognitive disturbance or HIV associated dementia;

wherein a level of acetyl spermine and/or acetyl spermidine that is similar to that of said standard value or that fits within said standard value range for mild neurocognitive disturbance or HIV associated dementia indicates that the patient suffers from mild neurocognitive disturbance or HIV associated dementia; and
(c) administering a treatment based on the disease status.

2. The method of claim 1 wherein said acetyl spermine and/or said acetyl spermidine level is detected by HPLC, mass spectroscopy or chromogenic sensing.

3. The method of claim 1 wherein said acetyl spermine and/or said acetyl spermidine is derivatized prior to being detected.

4. The method of claim 1 wherein said control sample is from a healthy subject without neurocognitive impairment or an HIV-1-infected subject without neurocognitive impairment.

5. The method of claim 1 wherein mild neurocognitive disturbance is detected.

6. The method of claim 1 wherein HIV associated dementia is detected.

7. The method of claim 1 wherein a level of said acetyl spermidine in said test sample that is from about 1.5-fold to about 2.5-fold that of the control sample indicates that the patient suffers from mild neurocognitive disturbance.

8. The method of claim 1 wherein a level of said acetyl spermidine in said test sample that is greater than about 2.6-fold that of the control sample indicates that the patient suffers from HIV-1-associated neurocognitive disorder.

9. The method of claim 1 wherein a level of said acetyl spermine in said test sample that is from about 3.0-fold to about 4.5-fold that of the control sample indicates that the patient suffers from mild neurocognitive disturbance.

10. The method of claim 1 wherein a level of said acetyl spermine in said test sample that is greater than about 4.6-fold that of the control sample indicates that the patient suffers from HIV associated dementia.

11. The method of claim 1 wherein a sum of the levels of said acetyl spermidine and said acetyl spermine in said test sample that is from about 2.5-fold to about 4.0-fold that of the control sample indicates that the patient suffers from mild neurocognitive disturbance.

12. The method of claim 1 wherein a sum of the levels of said acetyl spermidine and said acetyl spermine in said test sample that is greater than about 4.1-fold that of the control sample indicates that the patient suffers from HIV associated dementia.

13. The method of claim 1 wherein the control value for lack of neurocognitive impairment is 1.3 nmol/ml CSF for acetyl spermine, 1.8 nmol/ml CSF for acetyl spermidine or 3.1 nmol/ml CSF for the sum of acetyl spermidine and acetyl spermine.

14. The method of claim 1 wherein said acetyl spermine standard value for mild neurocognitive disturbance is from about 4.2 nmol/ml to about 6.0 nmol/ml CSF.

15. The method of claim 1 wherein said acetyl spermine control standard for HIV associated dementia is at least about 6.2 nmol/ml CSF.

16. The method of claim 1 wherein said acetyl spermidine standard for mild neurocognitive disturbance is from about 3.0 nmol/ml to about 4.0 nmol/ml CSF.

17. The method of claim 1 wherein said acetyl spermidine standard value for HIV associated dementia is at least about 5.0 nmol/ml CSF.

18. The method of claim 1 wherein said standard value for the sum of acetyl spermidine and acetyl spermine for mild neurocognitive disturbance is from about 7.2 nmol/ml to about 10.0 nmol/ml CSF.

19. The method of claim 1 wherein said standard value for the sum of acetyl spermidine and acetyl spermine for HIV associated dementia is at least about 11.2 nmol/ml CSF.

20. The method of claim 1 wherein said patient is female.

21. A method for monitoring the progression or improvement and treating of an HIV-1-associated neurocognitive disorder (HAND) in a patient comprising:
measuring the level of acetyl spermine and/or acetyl spermidine from a first cerebrospinal fluid test sample of said patient at a first time point;
and measuring the level of acetyl spermine and/or acetyl spermidine from a second cerebrospinal fluid test sample of said patient at a second time point;
wherein an elevated level of acetyl spermine and/or acetyl spermidine in said second test sample compared to the level of acetyl spermine or acetyl spermidine in said first test sample indicates that the HIV-1-associated neurocognitive disorder in said patient has progressed;
wherein a lower level of the acetyl spermine and/or acetyl spermidine in the second test sample compared to the level of acetyl spermine or acetyl spermidine in the first test sample indicates that the HIV-1-associated neurocognitive disorder in the patient has improved; and
wherein an unchanged level of the acetyl spermine and/or acetyl spermidine in the second test sample compared to the level of acetyl spermine or acetyl spermidine in the first test sample indicates that the HIV-1-associated neurocognitive disorder in the patient has not changed;
and administering a treatment based on the disease status.

22. The method of claim 21 wherein said acetyl spermine and/or said acetyl spermidine is detected by HPLC, mass spectroscopy or chromogenic sensing.

23. The method of claim 22 wherein said acetyl spermine and/or said acetyl spermidine is derivatized prior to being detected.

24. The method of claim 21 wherein said HIV-1-associated neurocognitive disorder is mild neurocognitive disturbance.

25. The method of claim 21 wherein said HIV-1-associated neurocognitive disorder is HIV associated dementia.

26. The method of claim 21 wherein said patient is female.

27. A method for staging and treating an HIV-1-associated neurocognitive disorder (HAND) in an HIV patient comprising:
measuring the level of acetyl spermine and/or acetyl spermidine in a cerebrospinal fluid test sample of a patient; and
comparing said level of acetyl spermine and/or acetyl spermidine to the level of acetyl spermine and/or acetyl spermidine in a sample of a control person without said HIV-1-associated neurocognitive disorder, a control from a person with a certain known stage of progression of said HIV-1-associated neurocognitive disorder, or to a series of standard values indicative of said stages;
determining which control sample or control standard has the most similar level of acetyl spermine or acetyl spermidine to that of said patient; and
assigning to said patient the stage of said control sample or standard value with the most similar level of acetyl spermine or acetyl spermidine to th

Assignees

• Univ Temple
• Univ Johns Hopkins
• Temple University—Of the Commonwealth System of Higher Education

Inventors

• Merali Salim
• Barrerro Carlos A
• Khalili Kamel
• Rappaport Jay
• Haughey Norman J
• Sacktor Ned

Classifications

• G01N33/5308

  for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites · CPC title

• G01N30/88

  Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 · CPC title

• G01N2800/2814

  Dementia; Cognitive disorders · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N2800/56

  Staging of a disease; Further complications associated with the disease · CPC title