PCSK9 Inhibitor Treatment for Patients With SPG5

Fujian Medical University (FJMU)

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Hereditary Spastic Paraplegia Type 5

Treatments: Drug: evolocumab

Study type: Interventional

Funder types: Other

Identifiers

NCT04101643

MRCTA, ECFAHofFMU[2019]209

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 14 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 14-80 years
• Probands with clinically manifest hereditary spastic paraplegia
• Genetically confirmed diagnosis of SPG5

Exclusion criteria

• Comprised treatment with statins 3 months prior to enrolment
• Contraindications to PCSK9 inhibitor therapy
• Pregnancy was excluded in women of childbearing age

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Evolocumab group

Experimental group

Description:

Eligible patients receive subcutaneous injections of evolocumab 420 mg

Treatment:

Drug: evolocumab