Spastic paraplegia type 5 (SPG5) is a rare subtype of hereditary spastic paraplegia, a highly
heterogeneous group of neurodegenerative disorders defined by progressive neurodegeneration
of the corticospinal tract motor neurons. SPG5 is caused by recessive mutations in the gene
CYP7B1 encoding oxysterol-7a-hydroxylase. This enzyme is involved in the degradation of
cholesterol into primary bile acids. CYP7B1 deficiency has been shown to lead to accumulation
of neurotoxic oxysterols. Oxysterols were found to impair metabolic activity and viability of
human cortical neurons at concentrations found in SPG5 patients, indicating that elevated
levels of oxysterols might be key pathogenic factors in SPG5. Monoclonal antibodies that
inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) have emerged as a new class of
drugs that effectively lower cholesterol levels. Evolocumab, a member of this class, is a
fully human monoclonal antibody that reduces LDL cholesterol levels by approximately 60%. We
thus performed this interventional trial with Evolocumab 420 mg for SPG5 patients.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
First Affiliated Hospital of Fujian Medical University