Aspartoacylase, Canavan Disease, Deficiency Disease, Infantile, Leukodystrophy, Spongiform
Conditions
Keywords
Leukodystrophy, Canavan disease,, Aspartoacylase,, Lithium,, Glyceryl Triacetate
Brief summary
The aim of this study is to determine whether oral supplementation with lithium and acetate may improve the biological and clinical prognosis in patients with Canavan Disease.
Detailed description
Canavan Disease is an autosomal recessive devastating demyelinating disease caused by a deficiency in Aspartoacylase (ASPA) enzyme. There is no available treatment. ASPA deficiency leads to:- the accumulation of high levels of N-acetylaspartate (NAA), involved in myelin degeneration and epilepsy;- the deficient synthesis of acetate in oligodendrocytes, that could impair CNS myelination.Lithium administration induces a decrease in NAA in the brain of the tremor rats (animal model for CD) and in one patient (JANSON, 2005). On the other hand, administration of acetate could improve myelination in Canavan patients.For this reason, we propose to combine both treatments: Lithium Gluconate and Glyceryl Triacetate (GTA). Eighteen patients, aged 1 to 15 years, will receive oral GTA or Lithium during 4 months, then both treatment in association during 6 months. Patients will be sequentially evaluated up to the end of the treatment and 2 months thereafter for:-tolerance of the therapy (careful monitoring of clinical and biological parameters).- efficacy of the therapy on clinical, biological and radiological parameters. Particularly, we will evaluate using MRI-spectroscopy and CSF samples the decrease in NAA and increase in acetate levels in the brain.
Interventions
DRUGLithium Gluconate (drug) Glyceryl Triacetate GTA (drug)
Lithium 1.3 mEq/kg/day (three administrations a day)during the study GTA 500 mg/kg/day in four administrations a day during the study
Sponsors
European Leukodystrophy Association
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* Clinical and biochemical diagnosis of Canavan disease
Exclusion criteria
* Renal disease * Thyroid disease * Cardiac disease * Impossibility to perform brain MRI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary outcome will be a decrease of the NAA peak (> 20%) or the appearance of an acetate peak at the end of the treatment (10 months), using spectroscopy-MRI. | 10 months |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcomes will be assessed at 10 months (end of the treatment): -Improvement of neuromotor performances (GMFM and Mullen scales), spasticity, and neurological severity | 10 months |
| -Improvement of epilepsy (number of seizures) | 10 months |
| -Decrease in NAA and increase in acetate contents in fluids (CSF, plasma, urine). | 10 months |
Outcome results
None listed