Preclinical Advances of Therapies for Laminopathies

Abstract

Laminopathies are a group of rare disorders due to mutation in LMNA gene. Depending on the mutation, they may affect striated muscles, adipose tissues, nerves or are multisystemic with various accelerated ageing syndromes. Although the diverse pathomechanisms responsible for laminopathies are not fully understood, several therapeutic approaches have been evaluated in patient cells or animal models, ranging from gene therapies to cell and drug therapies. This review is focused on these therapies with a strong focus on striated muscle laminopathies and premature ageing syndromes.

Keywords: HGPS; LMNA; lamin A/C; laminopathy; preclinical models; progerin; therapy; treatment.

Figure 1

Pathophysiological mechanisms involved in SML. Summary of physiological mechanisms affected in striated muscle laminopathies due to LMNA mutations. Black solid arrows indicate the consequence of altered mechanisms. Doted lines indicate correlation between mechanisms.

Figure 2

Pathophysiological mechanisms involved in premature aging syndromes. Summary of physiological mechanisms affected in premature aging syndromes due to LMNA mutations. Black solid arrows indicate the consequence of altered mechanisms. Doted lines indicate correlation between mechanisms.