PCSK9 Inhibitor Treatment for Patients With SPG5

Sponsor
First Affiliated Hospital of Fujian Medical University
Study ID
NCT04101643
Phase
PHASE1/PHASE2
Status
Unknown

Conditions

  • Hereditary Spastic Paraplegia Type 5

Eligibility Criteria

Sex
ALL
Age
14 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • evolocumab — DRUG
    Eligible patients receive subcutaneous injections of evolocumab 420 mg

Study Details

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.

Key Dates

Start date
Sep 29, 2019
Status verified
Nov 2021
Primary completion
Jan 3, 2023
Completion
Jan 3, 2023

Study Design

Enrollment
30 participants (estimated)
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Evolocumab group
    Eligible patients receive subcutaneous injections of evolocumab 420 mg

Primary Outcome Measure

The change of 27-hydroxycholesterol (27-OHC) [ Time Frame: up to 4 weeks ]

Central Contacts