Testing Miglustat Administration in Subjects With Spastic Paraplegia 11

IRCCS Fondazione Stella Maris10 enrolled

Overview

Hereditary spastic paraparesis type 11 (SPG11) is caused by mutations in the SPG11 gene that produces spatacsin, a protein involved in lysosomal function. Studies performed in skin cells (fibroblasts) from SPG11 patients, mice and zebrafish models of the disease showed that the material accumulated in the lysosomes is made of glycosphingolipids (GSL). Miglustat is a drug that inhibits an enzyme called glucosylceramide synthetase (GCS) which is used for the production of GSL. Miglustat, therefore, helps to delay the production of GSL. This study aims to collect preliminary data on the safety of miglustat on the SPG11 disease and to assess biomarkers.

We will analyze the safety of Miglustat

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Hereditary Spastic Paraparesis

Interventions

Eligibility

Sex: ALLMin age: 14 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Written signed informed consent; * Confirmed diagnosis of SPG11; * Age \> 13 years; * SPRS score ≥ 10 or ≤35; * Use of effective contraceptive methods and the performance of pregnancy tests (only fertile subjects). Exclusion Criteria: * Diagnosis of other concomitant neurodegenerative diseases; * Outcomes of severe pre- or peri-natal suffering; * Age ≤ 13 years; * SPRS score ≥ 35 or ≤10; * Hypersensitivity or intolerance to miglustat; * Participation in other pharmacological studies within 30 days of the first Study visit (T0); * The inability to take the drug; * Any additional medical conditions; * Subjects with severe renal impairment; * Refusal to use effective contraceptive methods and the performance of pregnancy tests (only fertile subjects).

Outcomes

Primary Outcomes

1-Changes from baseline blood tests at 24 weeks 2-Changes from baseline neurophysiological tests at 24 weeks 3-Report of severe adverse events

routine blood test

Time frame: At baseline, 24 weeks

Secondary Outcomes

Changes from baseline GM2/GM3 levels at 24 weeks

lipid assessments

Time frame: At baseline, 24 weeks

Assess changes in the scores of the Spastic Paraplegia Rating Scale (SPRS) at 24 weeks

SPRS rates disease severity (0-52) with lower numbers indicating less impairement

Time frame: At baseline, 24 weeks

Testing Miglustat Administration in Subjects With Spastic Paraplegia 11

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes