Methods and compositions to treat huntington's disease by targeting alox5- mediated ferroptosis
AssigneeThe Trustees of Columbia University in the City of New York
InventorWei GU
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Abstract
Disclosed herein are compositions and methods for treating or preventing Huntington's disease. In one aspect, the disclosed methods relate to targeting arachidonate 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (FLAP). The compositions and methods disclosed herein can be used as disease modifying therapies to enable treatment of Huntington's disease and related disorders earlier in disease progression and improve clinical outcomes.
Claims72
A method of treating or preventing Huntington's disease in a subject in need thereof, comprising administering to said subject a composition that targets an acyl-CoA synthetase long-chain family member 4 (ACSL4)-independent ferroptosis pathway.
A method of treating or preventing Huntington's disease in a subject in need thereof, comprising:
- (i) identifying the subject as expressing mutant huntingtin (mHTT), and
- (ii) administering to said subject a composition that targets an acyl-CoA synthetase long-chain family member 4 (ACSLA)-independent ferroptosis pathway.
A method of treating or preventing Huntington's disease in a subject in need thereof, comprising:
- (i) identifying the subject as having an increased expression level of arachidonate 5-lipoxygenase (ALOX5), and
- (ii) administering to said subject a composition that targets an acyl-CoA synthetase long-chain family member 4 (ACSL4)-independent ferroptosis pathway.
A method of treating or preventing Huntington's disease in a subject in need thereof, comprising:
- (i) identifying the subject as having an increased expression level of 5-lipoxygenase-activating protein (FLAP), and
- (ii) administering to said subject a composition that targets an acyl-CoA synthetase long-chain family member 4 (ACSLA)-independent ferroptosis pathway.
A composition for treating or preventing Huntington's disease, comprising a composition targeting the ACSLA-independent ferroptosis pathway.
A small interfering ribonucleic acid (siRNA) targeting the acyl-CoA synthetase long-chain family member 4 (ACSL4)-independent ferroptosis pathway.
A nucleic acid comprising a sequence encoding a short hairpin ribonucleic acid (shRNA) targeting the acyl-CoA synthetase long-chain family member 4 (ACSLA)-independent ferroptosis pathway.
A method of diagnosing Huntington's disease in a subject comprising:
- (i) determining the level of arachidonate 5-lipoxygenase (ALOX5) in the subject;
- and
- (ii) diagnosing the subject with Huntington's disease if the level of ALOX5 expression in the subject is increased as compared to a subject not suffering from Huntington's disease.
A method of diagnosing Huntington's disease in a subject comprising:
- (i) determining the level of 5-lipoxygenase-activating protein (FLAP) in the subject;
- and
- (ii) diagnosing the subject with Huntington's disease if the level of FLAP expression in the subject is increased as compared to a subject not suffering from Huntington's disease.
Dependencies are inferred from the claim text.