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US 2022/0065877 A1Published application
Use of GDF-15 in the Diagnosis and Treatment of Frailty and Conditions Associated with Altered Physiological Reserve, Physical Fitness and Exercise Capacity
AssigneeThe Chinese University of Hong Kong
InventorsErik Yee Mun George FUNG, Qi LI, Leong Ting LUI, Ronald Ching Wan MA, Jean WOO
Life of this patent
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Abstract
Provided herein are biomarkers useful for determining frailty, a biomarker signature for frailty, and methods of using the biomarkers to identify, classify, and treat a subject having frailty. Provided herein are also biomarkers useful for determining, identifying, classifying, and treating conditions associated with altered physical reserve, physical fitness, and exercise capacity.
Claims13
A method of treating frailty in a subject comprising the steps of
- a) measuring the levels of GDF-15 in a biological sample from the subject;
- and
- b) determining the subject as being frail if the level of the biomarker in the biological sample is higher than about 2,000 pg/ml to 6,000 pg/ml;
- pre-frail if the level of the biomarker in the biological sample is higher than 500 pg/ml to 2000 pg/ml;
- and robust if the level of the biomarker in the biological sample is less than 500 pg/ml;
- wherein if the subject is determined to be frail, treating the subject.
3 more elements
A method of treating frailty in a subject comprising the steps of:
- a) measuring the levels of GDF-15 in a biological sample from the subject;
- b) measuring the levels of one or more biomarkers selected from the group consisting of albumin, glutamine, GlycA, phosphoglycerides, glycine, and alanine;
- c) determining the overall biosignature score p;
- and
- d) determining the subject as being frail if p is Z;
- wherein Z is a value defined in Table 1 wherein the corresponding sensitivity and specificity values add up to between 1.4 and 1.5;
- wherein the score p is determined by
- i) inputting the subject's age in years;
- sex as value of 0 if female, 1 if male;
- and serum concentrations of biomarkers GDF-15 (pg/ml), albumin (g/1), glutamine (mmol/1), GlycA (mmol/1), phosphoglycerides (mmol/1), glycine (mmol/1), and alanine (mmol/1) of the subject into the following equation:
- p
- =
- exp
-
- (
- H
- )
- 1
- +
- exp
-
- (
- H
- )
- wherein
- H
- =
- (
- -
- 9
- .
- 3
-
- 1
- ±
- 0
- .
- 8
-
- 17
- ×
- sex
- +
- (
- 0.111
- ×
- age
- )
- +
- (
- 0.000121
- ×
- GDF
- -
- 15
- )
- +
- (
- 0.355
- ×
- Gln
- )
- +
- (
- 0
- .
- 5
-
- 71
-
- ×
- albumin
- )
- +
- (
- 0.526
- ×
- GlycA
- )
- +
- (
- -
- 0.
-
- 256
- ×
- phosphoglycerides
- )
- +
- (
- 0.266
- ×
- Gly
- )
- +
- (
- -
- 0.0577
- ×
- Ala
- )
- ;
- or
- ii) inputting the subject's age in years;
- sex as value of 0 if female, 1 if male;
- and log10-transformed serum concentrations of biomarkers GDF-15 (pg/ml), albumin (g/1), glutamine (mmol/1), GlycA (mmol/1), phosphoglycerides (mmol/1), glycine (mmol/1), and alanine (mmol/1) of the subject into the following equation:
- p
- =
- exp
-
- (
- H
- )
- 1
- +
- exp
-
- (
- H
- )
- wherein
- H
- =
- -
- 2
-
- 5
- .
- 5
-
- 4
- +
- (
- -
- 0.
-
- 95
- ×
- sex
- )
- +
- (
- 0.10
- ×
- age
- )
- +
- (
- 1.20
- ×
- GDF
- -
- 15
- )
- +
- (
- 7.26
- ×
- Gln
- )
- +
- (
- 1
-
- 0.0
-
- ×
- albumin
- )
- +
- (
- 6.30
- ×
- GlycA
- )
- +
- (
- -
- 3.
-
- 11
- ×
- phosphoglycerides
- )
- +
- (
- 3.22
- ×
- Gly
- )
- +
- (
- -
- 0.
-
- 97
- ×
- Ala
- )
-
- [
- [
- .
- ]
- ]
- ;
- wherein if the subject is determined to be frail, treating the subject.
204 more elements
(canceled)
A method of treating frailty in a subject comprising the steps of
- a) measuring the levels of GDF-15 in a biological sample from the subject;
- b) measuring the levels of NT-proBNP,
- wherein if NT-proBNP levels are elevated but GDF-15 levels are not, determining the subject has cardiac dysfunction without frailty;
- if GDF-15 levels are elevated but NT-proBNP are not, determining the subject has systemic physiological injury, hypoperfusion, diabetes mellitus, inflammatory disorders, or non-cardiac frailty;
- if both GDF-15 and NT-proBNP levels are elevated, determining the subject has frailty and is predicted to have heart failure and if neither NT-proBNP levels nor GDF-15 levels are elevated, determining the subject is at low risk for frailty and low risk for heart failure;
- and
- c) treating the subject with a guideline-directed medical therapy (GDMT);
- wherein if the subject has elevated levels of both NT-proBNP and GDF-15, treating the subject as advanced stage D in accordance with GDMT;
- if the subject has elevated levels of NT-proBNP but not elevated levels of GDF-15, conducting cardiac imaging to determine the causes of cardiac dysfunction and treating the cardiac dysfunction in accordance with stage B or C in accordance with GDMT;
- if the subject has elevated levels of GDF-15 but not elevated levels of NT-proBNP, conducting a clinical assessment of medical comorbidities and treating the subject in accordance with stage B or C in accordance with GDMT;
- and if the subject does not have elevated levels of either NT-proBNP or GDF-15, treating the patient with as stage A in accordance with GDMT.
8 more elements
10-11. (canceled)
14-16. (canceled)
Dependencies are inferred from the claim text.