Hereditary Spastic Paraparesis
Conditions
Keywords
Autophagic Lysosome Reformation, SPG11, Miglustat, Lisosomal Storage Disorders
Brief summary
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.
Detailed description
We will analyze the safety of Miglustat
Interventions
DRUGMiglustat 100 MG
100mg/TID in 4w then 200mg/TID in 8 w
Sponsors
IRCCS Fondazione Stella Maris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-Changes from baseline blood tests at 24 weeks 2-Changes from baseline neurophysiological tests at 24 weeks 3-Report of severe adverse events | At baseline, 24 weeks | routine blood test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline GM2/GM3 levels at 24 weeks | At baseline, 24 weeks | lipid assessments |
| Assess changes in the scores of the Spastic Paraplegia Rating Scale (SPRS) at 24 weeks | At baseline, 24 weeks | SPRS rates disease severity (0-52) with lower numbers indicating less impairement |
Countries
Italy
Outcome results
None listed