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US 2025/0093370 A1Published application
Biomarkers and their use in diagnosing parkinson's disease, vitreoretinal diseases, and age-related pathologies
OwnerVinit Mahajan, Julian Wolfinventors
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Abstract
Compositions, methods, and kits are provided for diagnosing Parkinson's disease, vitreoretinal diseases, and age-related pathologies. In particular, aqueous humor biomarkers have been identified that correlate with biological aging and age-related pathologies and morbidity. The use of such biomarkers may allow earlier intervention in treatment of aging-related diseases. In addition, methods of using aqueous humor biomarkers for prognosis, diagnosis, and monitoring treatment of Parkinson's disease and vitreoretinal diseases are also provided.
Claims28
A method of diagnosing and treating retinitis pigmentosa in a patient, the method comprising:
- obtaining an aqueous humor sample from an eye of the patient;
- measuring levels of at least two, at least three, or at least four biomarkers selected from RS1, SAG, SPINK4, FUT3, GDF10, LRIT2, FAIM, CDHR1, RCVRN, GSKIP, EYS, NPPC, HES6, FGF23, AP4M1, GUCA1A, SPATA33, MPPED2, ASIC4, JPH4, CPNE7, TENM4, GRM4, TNKS, GAD1, SV2A, SYT5, RIC3, CAMK2A, LRRTM4, KCNG4, DPP10, PPP1R27, RGS5, GRAP, RAMP3, MEOX1, AFAP1 L1, OPCML, LRIT3, PLA2G5, GALNT11, and KCTD4 in the aqueous humor sample, wherein decreased levels of the one or more biomarkers selected from RS1, SAG, SPINK4, FUT3, GDF10, LRIT2, FAIM, CDHR1, RCVRN, GSKIP, EYS, NPPC, HES6, FGF23, AP4M1, GUCA1A, SPATA33, MPPED2, ASIC4, JPH4, CPNE7, TENM4, GRM4, TNKS, GAD1, SV2A, SYT5, RIC3, CAMK2A, LRRTM4, KCNG4, DPP10, PPP1R27, RGS5, GRAP, RAMP3, MEOX1, AFAP1L1, OPCML, LRIT3, PLA2G5, GALNT11, and KCTD4 compared to reference value ranges for the levels of the one or more biomarkers in a control aqueous humor sample indicate that the patient has retinitis pigmentosa;
- and
- treating the patient for the retinitis pigmentosa if the patient has a positive diagnosis for retinitis pigmentosa.
1 more element
A method of diagnosing and treating diabetic retinopathy in a patient, the method comprising:
- obtaining an aqueous humor sample from an eye of the patient;
- measuring levels of at least two, at least three, or at least four biomarkers selected from LBP, CRP, ITIH3, APOA1, CPN2, C4BPA, HABP2, F13B, SERPINA10, IGFBP1, FN1, MMP19, ANGPT2, ROBO4, VEGFD, ANGPTL4, FLT4, FLNA, EPHA1, ENG, THBS1, CLIC4, NRP2, VEGFA, WARS1, CXCL8, TYMP, CCL2, MAPK14, and AKT1 in the aqueous humor sample, wherein increased levels of the one or more biomarkers selected from LBP, CRP, ITIH3, APOA1, CPN2, C4BPA, HABP2, F13B, SERPINA10, IGFBP1, FN1, MMP19, ANGPT2, ROBO4, VEGFD, ANGPTL4, FLT4, FLNA, EPHA1, ENG, THBS1, CLIC4, NRP2, VEGFA, WARS1, CXCL8, TYMP, CCL2, MAPK14, and AKT1 compared to reference value ranges for the levels of the one or more biomarkers in a control aqueous humor sample indicate that the patient has diabetic retinopathy;
- and
- treating the patient for the diabetic retinopathy if the patient has a positive diagnosis for diabetic retinopathy.
1 more element
A method of monitoring a patient having non-proliferative diabetic retinopathy for progression to proliferative diabetic retinopathy, the method comprising:
- obtaining an aqueous humor sample from an eye of the patient;
- measuring levels of one or more biomarkers selected from THBS1, CLIC4, NRP2, VEGFA, WARS1, CXCL8, TYMP, CCL2, MAPK14, and AKT1 in the aqueous humor sample, wherein increased levels of the one or more biomarkers selected from THBS1, CLIC4, NRP2, VEGFA, WARS1, CXCL8, TYMP, CCL2, MAPK14, and AKT1 compared to reference value ranges for the levels of the one or more biomarkers in a control aqueous humor sample indicate that the patient has proliferative diabetic retinopathy.
A method of distinguishing between a diagnosis of non-proliferative diabetic retinopathy and proliferative diabetic retinopathy for a patient, the method comprising:
- obtaining an aqueous humor sample from an eye of the patient;
- measuring levels of one or more biomarkers selected from FN1, MMP19, ANGPT2, ROBO4, VEGFD, ANGPTL4, FLT4, FLNA, EPHA1, and ENG in the aqueous humor sample, wherein increased levels of the one or more biomarkers selected from FN1, MMP19, ANGPT2, ROBO4, VEGFD, ANGPTL4, FLT4, FLNA, EPHA1, and ENG compared to reference value ranges for the levels of the one or more biomarkers in a control aqueous humor sample indicate that the patient has non-proliferative diabetic retinopathy;
- and
- measuring levels of one or more biomarkers selected from THBS1, CLIC4, NRP2, VEGFA, WARS1, CXCL8, TYMP, CCL2, MAPK14, and AKT1 in the aqueous humor sample, wherein increased levels of the one or more biomarkers selected from THBS1, CLIC4, NRP2, VEGFA, WARS1, CXCL8, TYMP, CCL2, MAPK14, and AKT1 compared to reference value ranges for the levels of the one or more biomarkers in a control aqueous humor sample indicate that the patient has proliferative diabetic retinopathy.
1 more element
A method of diagnosing and treating Parkinson's disease in a patient, the method comprising:
- obtaining an aqueous humor sample from an eye of the patient;
- measuring levels of at least two, at least three, or at least four biomarkers selected from TRIO, JPH4, CPNE7, GRM4, TNKS, SERAC1, ACVR2B, SV2A, RIC3, CAMK2A, BCL2L2, DBNDD1, SULT4A1, HABP4, SNPH, RAC3, SYT13, PAK5, NTRK1, C1QL4, KCNG4, DPP10, PPP1R27, PIH1D2, CDHR1, C17orf67, GSKIP, CEP112, HES6, FGF23, AP4M1, SPATA33, MPPED2, CHRNA5, and ASIC4 in the aqueous humor sample, wherein decreased levels of the one or more biomarkers selected from TRIO, JPH4, CPNE7, GRM4, TNKS, SERAC1, ACVR2B, SV2A, RIC3, CAMK2A, BCL2L2, DBNDD1, SULT4A1, HABP4, SNPH, RAC3, SYT13, PAK5, NTRK1, C1QL4, KCNG4, DPP10, PPP1R27, PIH1D2, CDHR1, C17orf67, GSKIP, CEP112, HES6, FGF23, AP4M1, SPATA33, MPPED2, CHRNA5, and ASIC4 compared to reference value ranges for the levels of the one or more biomarkers in a control aqueous humor sample indicate that the patient has Parkinson's disease;
- and
- treating the patient for the Parkinson's disease if the patient has Parkinson's disease.
1 more element
A method of diagnosing and treating uveitis in a patient, the method comprising:
- obtaining an aqueous humor sample from an eye of the patient;
- measuring levels of at least two, at least three, or at least four biomarkers selected from IGHM, TXNDC5, SLAMF7, MZB1, IGHD, CR2, IGHG4, LY9, FCRL5, TNFRSF13B, MMP9, IL1R2, GLIPR2, MPO, RETN, CD177, PSTPIP1, CLEC12A, HMGB2, LTA4H, VWF, TIE1, SELE, CDH5, ANGPT2, FLT4, ADGRF5, VEGFC, TEK, MYCT1, CXCL10, IL18BP, CCL22, TNFRSF8, CCL7, MMP12, IL10, CXCL11, CELA1, GNLY, CST7, CD8A, CD5, GZMK, GZMA, CCL5, CD7, LCK, and SH2D1A in the aqueous humor sample, wherein increased levels of the one or more biomarkers selected from IGHM, TXNDC5, SLAMF7, MZB1, IGHD, CR2, IGHG4, LY9, FCRL5, TNFRSF13B, MMP9, IL1R2, GLIPR2, MPO, RETN, CD177, PSTPIP1, CLEC12A, HMGB2, LTA4H, VWF, TIE1, SELE, CDH5, ANGPT2, FLT4, ADGRF5, VEGFC, TEK, MYCT1, CXCL10, IL18BP, CCL22, TNFRSF8, CCL7, MMP12, IL10, CXCL11, CELA1, GNLY, CST7, CD8A, CD5, GZMK, GZMA, CCL5, CD7, LCK, and SH2D1A compared to reference value ranges for the levels of the one or more biomarkers in a control aqueous humor sample indicate that the patient has uveitis;
- and
- treating the patient for the uveitis if the patient has a positive diagnosis for uveitis.
1 more element
A method of determining biological age of an eye in a patient, the method comprising:
- obtaining an aqueous humor sample from an eye of the patient;
- and
- measuring levels of at least two, at least three, or at least four biomarkers selected from LECT2, DCBLD1, SCGN, ACAN, AOC2, CAPS, TFF3, AMN, ABO, NETO1, CD274, PPBP, ABL1, HAMP, IGFBP1, AAMDC, A1BG, ADA2, MVP, CRYGC, A4GALT, A4GNT, AADAT, A2M, and ABI3 in the aqueous humor sample;
- and
- using a machine learning aging model to determine the biological age of the eye based on the levels of the one or more biomarkers selected from LECT2, DCBLD1, SCGN, ACAN, AOC2, CAPS, TFF3, AMN, ABO, NETO1, CD274, PPBP, ABL1, HAMP, IGFBP1, AAMDC, A1BG, ADA2, MVP, CRYGC, A4GALT, A4GNT, AADAT, A2M, and ABI3.
2 more elements
Dependencies are inferred from the claim text.