Systematic in vivo candidate evaluation uncovers therapeutic targets for LMNA dilated cardiomyopathy and risk of Lamin A toxicity

Table 1 Effect of potential candidates on Lmna DCM in mice

Age	Virus	N	LVDD	P	LVWT	P	EF%	P	FS%	P
5.5 weeks	Ctrl	5	3.93 ± 0.16		0.69 ± 0.06		52.88 ± 4.73		26.86 ± 2.95
	Lmna DCM + Ctrl	5	4.30 ± 0.12		0.55 ± 0.05		18.57 ± 1.96		8.32 ± 0.91
	Lmna DCM + Lamin A	5	3.98 ± 0.24	1.34E-02	0.62 ± 0.02	9.66E-02	39.41 ± 4.38	1.91E-04	18.88 ± 2.46	7.61E-04

Age	Virus	N	LVDD	P	LVWT	P	EF%	P	FS%	P
5.5 weeks	Ctrl	5	3.93 ± 0.05		0.68 ± 0.03		55.25 ± 3.90		28.34 ± 2.57
	Lmna DCM + Ctrl	5	4.27 ± 0.12		0.52 ± 0.03		18.39 ± 2.80		8.24 ± 1.31
	Lmna DCM + Lamin C	5	3.97 ± 0.15	2.01E-02	0.67 ± 0.03	3.20E-04	46.68 ± 3.20	1.20E-06	23.03 ± 2.00	7.03E-06

Echocardiography of Lmna DCM mice with Lamin A (top panel) and Lamin C (bottom panel) upregulation at a dose of 1E + 13 vg/kg assessed at 5.5 weeks. P value represents comparisons to Lmna DCM, Brown-Forsythe and Welch ANOVA test with Dunnett’s T3 correction. LVDD, left ventricular diastolic dimension; LVWT, LV wall thickness; EF, ejection fraction; FS, fractional shortening

ISSN: 1479-5876