Hdl therapy markers

A method for monitoring the efficacy of a HDL Therapeutic in a subject, comprising:

• (a) treating a subject with a HDL Therapeutic according to a first dosing schedule,
• (b) measuring expression levels of one or more HDL Markers in said subject's circulating monocytes, macrophages or mononuclear cells to evaluate the effect of said first dosing schedule on said expression levels;
• and
• (c) (i) if the subject's expression levels of one or more HDL Markers are reduced by more than an upper cutoff amount, treating the subject with the HDL Therapeutic according to a second dosing schedule, wherein the second dosing schedule comprises one or more of:
• administering a lower dose of the HDL Therapeutic, infusing the HDL Therapeutic into the subject over a longer period of time, and administering the HDL Therapeutic to the subject on a less frequent basis;
• (ii) if the subject's expression levels of one or more HDL Markers are not reduced by more than a lower cutoff amount, treating the subject with the HDL Therapeutic according to a second dosing schedule, wherein the second dosing schedule comprises one or more of:
• administering a higher dose of the HDL Therapeutic, infusing the HDL Therapeutic into the subject over a shorter period of time, and administering the HDL Therapeutic to the subject on a more frequent basis;
• or
• (iii) if the subject's expression levels of one or more HDL Markers are reduced by an amount between the upper and lower cutoff amounts, continuing to treat the subject according to the first dosing schedule.

A method of identifying a dose of a HDL Therapeutic effective to mobilize cholesterol, comprising:

• (a) administering a first dose of a HDL Therapeutic to a population of subjects,
• (b) following administering said first dose, measuring expression levels of one or more HDL Markers in said subjects' circulating monocytes, macrophages or mononuclear cells to evaluate the effect of said first dose on said expression levels;
• (c) administering a second dose of said HDL Therapeutic, wherein the second dose of said HDL Therapeutic is greater or lower than the first dose,
• (d) following administering said second dose, measuring expression levels of one or more HDL Markers in said subjects' circulating monocytes, macrophages or mononuclear cells to evaluate the effect of said first and/or second dose on said expression levels;
• (e) optionally repeating steps (c) and (d) with one or more additional doses of said HDL Therapeutic;
• and
• (f) identifying the highest dose that does not reduce expression levels of one or more HDL Markers in by more than a cutoff amount, thereby identifying a dose of said HDL Therapeutic effective to mobilize cholesterol.

A method for treating a subject in need of an HDL Therapeutic, comprising administering to subject a combination of:

• I. (a) an HDL Therapeutic, which is optionally a lipoprotein complex, in a dose that does not reduce expression of one or more HDL Markers in said subject's circulating monocytes, macrophages or mononuclear cells by more than 20% or more than 10% as compared to the subject's baseline amount;
• and
• (b) a cholesterol reducing therapy, optionally selected from a bile-acid resin, niacin, a statin, a fibrate, a PCSK9 inhibitor, ezetimibe, and a CETP inhibitor;
• or
• II. (a) an HDL Therapeutic, which is optionally a lipoprotein complex, in a dose that does not reduce expression of one or more HDL Markers in said subject's circulating monocytes, macrophages or mononuclear cells by more than 20% or more than 10% as compared to a control amount;
• and
• (b) a cholesterol reducing therapy, optionally selected from a bile-acid resin, niacin, a statin, a fibrate, a PCSK9 inhibitor, ezetimibe, and a CETP inhibitor.

A method of identifying a dose of a HDL Therapeutic suitable for therapy, comprising:

• I. (a) administering one or more doses of a HDL Therapeutic to a subject,
• (b) measuring expression levels of one or more HDL Markers in said subject's circulating monocytes, macrophages or mononuclear cells following each dose;
• and
• (c) identifying the maximum dose that does not raise expression levels of said one or more HDL Markers by more than 0%, more than 10% or more than 20%, thereby identifying a dose of a HDL Therapeutic suitable for therapy;
• II. (a) administering one or more doses of a HDL Therapeutic to a population of subjects,
• (b) measuring expression levels of one or more HDL Markers in said subjects' circulating monocytes, macrophages or mononuclear cells following each dose;
• and
• (c) identifying the maximum dose that does not raise expression levels of said one or more HDL Markers by more than 0%, more than 10% or more than 20% in said subjects, thereby identifying a dose of a HDL Therapeutic suitable for therapy;
• III. identifying the highest dose of the HDL therapeutic that does not reduce cellular cholesterol efflux by more than 0%, more than 10% or more than 20%;
• IV. identifying the highest dose of the HDL therapeutic that does not reduce cellular cholesterol efflux by more than 0%, more than 10% or more than 20% by
• (a) administering one or more doses of a HDL Therapeutic to a subject or population of subjects;
• (b) measuring cholesterol efflux in cells from said subject or population of subjects;
• and
• (c) identifying the maximum dose that does not reduce cholesterol efflux by more than 0%, more than 10% or more than 20% in said subjects, thereby identifying a dose of a HDL Therapeutic suitable for therapy;
• or
• V. (a) administering one or more doses of the HDL Therapeutic to a subject or to a population of subjects,
• (b) measuring expression levels of one or more HDL Markers in said subject's or population's circulating monocytes, macrophages or mononuclear cells following each dose;
• and
• (c) identifying a dose that maintains baseline expression levels or raises the expression levels of one or more HDL Markers in the subject's circulating monocytes, macrophages or mononuclear cells, thereby identifying a dose of an HDL Therapeutic suitable for therapy.

A method of identifying a dosing interval of a HDL Therapeutic suitable for therapy, comprising identifying the highest dose of the most frequent dosing regimen of the HDL therapeutic that does not reduce cellular cholesterol efflux by more than 0%, more than 10% or more than 20%, wherein the method optionally comprises:

• (a) administering a HDL Therapeutic to a subject or population of subjects according to one or more dosing frequencies;
• (b) measuring cholesterol efflux in cells from said subject or population of subjects;
• and
• (c) identifying the maximum dosing frequency that does not reduce cholesterol efflux by more than 0%, more than 10% or more than 20% in said subjects, thereby identifying a dose of a HDL Therapeutic suitable for therapy.