Biomarkers for huntington disease stratification, methods and uses thereof

A HD biomarker panel, the panel comprising:

• (a) ALB alone;
• (b) C4B alone;
• (c) IGHG1 alone;
• (d) TTR alone;
• (e) CNR1 alone;
• (f) PDYN alone;
• (g) PENK alone;
• (h) PPP1R1B alone;
• (i) APOE alone;
• (j) BDNF alone;
• (k) C1QB alone;
• (l) C7 alone;
• (m) FAT2 alone;
• (n) GNAL alone;
• (o) IGF2 alone;
• (p) NEFL alone;
• (q) PENK with ALB;
• (r) PENK with ALB and one of NEFL, IGF2, C7, BDNF, APOE, and IGHG1;
• (s) PENK with IGHG1 and NEFL;
• or
• (t) PENK with IGF2 and C7;
• wherein the biomarker panel is indicative of early biochemical changes in HD.

A HD biomarker panel, the panel comprising:

• (a) CHI3L1 alone;
• (b) C4B with IGHG1;
• (c) C4B, IGHG1, and NEFL;
• (d) CHI3L1 with C4B, IGHG1, and ALB;
• (e) PPP1R1B alone;
• (f) PPP1R1B with TTR;
• (g) TTR and CHI3L1 with one of:
• CTSD;
• and PPP1R1B;
• (h) C4B, TTR, and CNR1;
• (i) PPP1R1B, TTR, CTSD with one of:
• CHI3L1;
• ALB;
• C4B;
• and C1QB;
• (j) TTR, CHI3L1, and CTSD with one of:
• ALB;
• CYCS;
• CNR1;
• and C1QB;
• (k) TTR, ALB, and CYCS with one of:
• C4B;
• and PPP1R1B;
• (l) TTR, CTSD, and CYCS with one of:
• ALB;
• and C1QB;
• (m) C4B, TTR, CTSD, and CNR1;
• (n) C1QB, TTR, CTSD, and CNR1;
• (o) C1QB alone;
• (p) C4B alone;
• or
• (q) TTR alone;
• wherein the biomarker panel is for following the transition from pre-manifest HD to manifest HD.

A HD biomarker panel, the panel comprising:

• (a) PDYN;
• (b) PDYN with PENK;
• (c) PDYN and IGHG1 with one of:
• PENK;
• and C1QB;
• (d) PENK, CNR1, and IGF2;
• (e) CNR1, C1QB, and IGHG1;
• (f) CNR1, PPP1R1B, APOE, and IGHG1;
• (g) CNR1, PPP1R1B, BDNF;
• APOE, and IGHG1;
• (h) CNR1, BDNF;
• APOE, IGF2, and IDO1;
• (i) CNR1, BDNF;
• C1QB, IGF2, and IDO1;
• (j) CNR1, PPP1R1B, BDNF;
• C1QB, and IGHG1;
• (k) PDYN, CNR1, PPP1R1B, C1QB, and IGHG1;
• (l) APOE;
• (m) BDNF;
• (n) C1QB;
• (o) CNR1;
• (p) IDO1;
• (q) IGF2;
• (r) IGHG1;
• (s) NEFL;
• (t) PENK;
• (u) PP1R1B;
• or
• (v) TTR;
• wherein the biomarker panel is for monitoring progression of HD or severity of HD or progression and severity of HD.

A method for monitoring response to treatment of HD and determining treatment efficacy in a subject, comprising the steps of:

• (a) measuring levels of at least one biomarker in at least 2 longitudinal biological samples from the same subject and comparing the measured levels to an level of a matched biomarker determined in a clinically relevant population, wherein the at least one biomarker is from a first panel, comprising:
• NEFL;
• GNAL;
• DRD1;
• IGF2;
• IGHG1;
• CHI3L1;
• C7;
• FAT2;
• ALB;
• PDE10A;
• CLU;
• C4B;
• CYCS;
• DRD2;
• SIGMAR1;
• TTR;
• Q1QC;
• ID01;
• CNR1;
• CTSD;
• C1QB;
• PPP1R1B;
• APOE;
• BDNF;
• PDYN;
• and PENK, wherein the level of the one or more biomarkers in the biological sample is changed, and wherein at least one of the at least two biological samples is collected before the individual is treated for HD and at least one of the at least two biological samples is collected after the subject is treated for HD;
• (b) calculating a score for the at least one biomarker in the biological samples, by summing:
• the number of biomarkers in the first panel exhibiting a change in level relative to the of the biomarker determined in a clinically relevant population, and/or the number of biomarkers in the second panel exhibiting a change in level relative to the of the biomarker determined in a clinically relevant population;
• and
• (c) determining that said treatment(s) is effective if the score of the panel of biomarker(s) in the sample collected after treatment is lower than the score of at least one of the at least two biologicals samples collected before treatment.