efficacy metazym for the treatment metachromatic leukodystrophy treated with hematopoietic stem cell transplantation

Conditions: Metachromatic Leukodystrophy

Summary: there is currently no effective treatment for late infantile mld once clinical symptoms are evident. metazym is a recombinant human arylsulfatase a developed for an intravenous ert for the treatment of late infantile mld. the overall objective of this study is to evaluate the efficacy and safety of intravenous rhasa treatment in a patient with late infantile mld who had previously received hematopoietic stem cell transplantation (hct).

metachromatic leukodystrophy (mld) is a rare autosomal recessive disorder caused by the deficiency of the arylsulfatase a enzyme (arsa), resulting in accumulation of galactosyl sulfatide (cerebroside sulfate), a major constituent of the myelin sheath. accumulation of galactosyl sulfatides leads to a progressive degeneration of the white matter in the central and peripheral nervous system (cns, pns) and neuronal degeneration. the late infantile form of mld, which usually is diagnosed in the second year of life, is the most frequent and severe form of the disease. the prognosis is severe, leading to vegetative stage or death within few years after the diagnosis. there is no treatment for patients affected with this early onset form of the disease. in patients with late-onset mld (juvenile and adult forms), allogeneic hematopoietic stem cell transplantation can stabilize the cerebral demyelination. this treatment is however inefficient in patients with late infantile mld at a symptomatic stage. the overall objective is to evaluate the efficacy and safety of rhasa treatment in a patient with late infantile mld who had received hct at a presymptomatic stage of the disease. patient will receive rharsa (100 u/kg) intravenously every other week for a period of 18 months.

Eligibility criteria:
inclusion criteria: * subject's legally authorized guardian(s) must provide signed, informed consent prior to performing any study-related activities. * the patient must have a confirmed diagnosis of mld as defined by:arsa activity \< 10 nmol/h/mg in leukocytes prior to hct; presence of elevated sulfatide in urine prior to hct * the patient must have a residual level of voluntary function (as judged by the investigator), including presence of residual cognitive function (attention, executive and visual functions) as well as the presence of residual voluntary motor function in one upper or lower limb as a minimum. * the patient must have an age at the time of screening ≥ 6 months * the patient must have had onset of symptoms before the age of 4 years * the subject and his/her guardian(s) must have the ability to comply with the clinical protocol * the patients' medical record must document that the legal guardian(s) has had independent counselling or a consultation regarding stem cell transplantation in order to assure that the guardian(s) is fully informed regarding the risks and benefits of this alternative exclusion criteria: patient will be excluded from this study if they do not meet the specific inclusion criteria, or if any of the following criteria apply: * presence of a gross motor function measure (gmfm \< 25) * presence of severe pseudo-bulbar signs (weakness and disco-ordination of tongue and swallowing muscles leading to severe difficulty with swallowing) * spasticity so severe to inhibit transportation * known multiple sulfatase deficiency * presence of major congenital abnormality * presence of known chromosomal abnormality and syndromes affecting psychomotor development * presence of known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition * any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the investigator, would preclude participation in the trial * use of any investigational product within 30 days prior to study enrolment or currently enrolled in another study which involves clinical investigations * received ert with rhasa from any source

Keywords: metachromatic leukodystrophy enzyme replacement therapy allogeneic hematopoietic stem cell transplantation