Frataxin-sensitive lipid markers for monitoring frataxin replacement therapy
AssigneeLarimar Therapeutics, Inc.
InventorsJoan David Bettoun, Christine Des Rosiers, Anik Forest
Life of this patent
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Abstract
The present disclosure is based, at least in part, on providing a set of markers, also referred to herein as FXN-sensitive lipid markers (or FSLMs), the respective levels of which are positively or negatively correlated to frataxin (FXN) levels in a cell. Therefore, these FSLMs can be used to determine, evaluate, and/or monitor the effectiveness of FXN replacement therapy in a subject.
Claims67
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A method for evaluating efficacy of a frataxin (FXN) replacement therapy, the method comprising:
- (a) determining an FXN replacement lipid profile for one or more FXN-sensitive lipid markers (FSLMs) in a sample obtained from an FXN deficient subject following administration of an FXN replacement therapy;
- (b) comparing the subject FXN replacement lipid profile determined in step (a) with a reference FXN lipid profile for the one or more FSLMs;
- and
- (c) determining efficacy of the FXN replacement therapy based on the comparison in step (b);
- wherein the one or more FSLMs are selected from a group consisting of one or more of:
- triglycerides (TGs), wherein the three acyl groups in each triglyceride molecule contain less than 56 carbons and/or wherein the three acyl groups in each triglyceride molecule contain 7 or less unsaturations;
- ether phospholipids;
- phosphatidylcholines (PCs);
- cholesteryl esters (CEs);
- and
- diglycerides (DGs).
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16-18. (canceled)
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27-29. (canceled)
32-38. (canceled)
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A method of monitoring treatment of a subject with a frataxin (FXN) replacement therapy, the method comprising:
- (a) determining a first FXN replacement lipid profile for one or more FXN-sensitive lipid markers (FSLMs) in a first sample obtained from an FXN deficient subject at a first time point following administration of an FXN replacement therapy to the subject,
- (b) determining a second FXN replacement lipid profile for the one or more FXN-sensitive lipid markers (FSLMs) in a second sample obtained from the subject at a second time point that is later than the first time point;
- (c) comparing the second FXN replacement lipid profile with the first FXN replacement profile;
- thereby monitoring treatment of the subject with the FXN replacement therapy;
- wherein the one or more FSLMs are selected from a group consisting of one or more of:
- triglycerides (TGs), wherein the three acyl groups in each triglyceride molecule contain less than 56 carbons and/or wherein the three acyl groups in each triglyceride molecule contain 7 or less unsaturations;
- ether phospholipids;
- phosphatidylcholines (PCs)
- cholesteryl esters (CEs);
- and
- diglycerides (DGs).
47-61. (canceled)
A method for treating an FXN deficiency, the method comprising:
- (a) determining an FXN lipid profile in a sample obtained from an FXN deficient subject for one or more FXN-sensitive lipid markers (FSLMs),
- (b) comparing the FXN lipid profile of the sample with at least one other lipid profile selected from the group consisting of normal FXN lipid profile for the one or more FSLMs, baseline FXN(−) lipid profile for the one or more FSLMs, and FXN replacement lipid profile for the one or more FSLMs,
- (c) classifying the FXN lipid profile determined in step (a) as corresponding to a normal FXN lipid profile, baseline FXN(−) lipid profile or an FXN replacement lipid profile, and
- (d) initiating or modulating an FXN replacement therapy based on the classification of the FXN lipid profile of the sample.
A method of treating an FXN deficiency in a subject, comprising:
- (a) determining an FXN lipid profile for one or more FXN-sensitive lipid markers (FSLMs) in a sample from an FXN deficient subject;
- and
- (b) recommending to a healthcare provider to administer an FXN replacement therapy to the subject based on the subject FXN lipid profile determined in step (a).
A method of treating an FXN deficiency in a subject, comprising:
- (a) obtaining an FXN lipid profile for one or more FSLMs in a sample obtained from an FXN deficient subject;
- and
- (b) administering an FXN replacement therapy to the subject based on the subject FXN lipid profile.
67-68. (canceled)
A method of detecting one or more frataxin-sensitive lipid markers (FSLMs) in a sample from a frataxin (FXN) deficient subject, comprising
- subjecting the sample, or a portion thereof, to analysis by mass spectrometry, wherein the one or more FSLMs are selected from a group consisting of:
- triglycerides (TGs), wherein the three acyl groups in each triglyceride molecule contain less than 56 carbons and/or wherein the three acyl groups in each triglyceride molecule contain 7 or less unsaturations;
- ether phospholipids;
- phosphatidylcholines (PCs);
- cholesteryl esters (CEs);
- and
- diglycerides (DGs).
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88-90. (canceled)
A kit for detecting one or more frataxin-sensitive lipid markers (FSLMs) in a sample obtained from a frataxin (FXN) deficient subject, comprising
- one or more isotopically labeled lipids for use as internal standards in a mass spectrometry-based analysis for detecting one or more FSLMs in the sample, and
- a set of instructions for detecting the level of the one or more FSLMs in the sample from the subject by mass spectrometry.
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Dependencies are inferred from the claim text.