LMNA-associated congenital muscular dystrophy (L-CMD) is a rare genetic disease caused by point mutations in the LMNA gene and currently lacks a cure. This debilitating disease is characterized by muscle weakness, hypotonia, joint contractures, respiratory insufficiency, spinal rigidity, and cardiac anomalies that can lead to sudden death. The goal of this study is to develop effective gene therapies for L-CMD. Three different approaches were explored: over-expression of an exogenous LMNA wild type form, HITI technology, and CRISPR-mediated specific elimination of the mutant allele. AAV9 vectors were utilized as delivery vectors, and the effectiveness of the gene therapy approaches was assessed in mice with either one or two copies of the Lmna c.745C>T, p.R249W mutation, which presented with either a late onset cardiomyopathy phenotype or an early onset metabolic phenotype, respectively. A single, preventive dose of AAV9 particles for any of the three gene therapy approaches significantly increased the median survival of homozygous Lmnaᴿ²⁴⁹ᵂ/ᴿ²⁴⁹ᵂ mice in the metabolic scenario. However, heterozygous mice, which present a cardiomyopathy phenotype, responded differently to each therapy, with over-expression and HITI therapies leading to worse survival. The AAV9 delivery of Cas9 plus sgRNA specific for the c.745C>T mutation demonstrated clear survival benefits. These findings confirm the potential of gene therapy for L-CMD treatment and highlight the importance of carefully evaluating and selecting the appropriate approach.