Clinical trials addressing different leukodystrophies

Find the latest information related to clinical trials addressing different leukodystrophies in a single trial.

Status: Patient Recruitment
Drug: L-DOPA
Objective: To assay the effectiveness of L-DOPA in improving akinetic-rigid symptoms occurring in several leukodystrophies

Start date: July 2013
Estimated completion date: July 2014
On-going data analysis

Director of the study: Vincenzo Leuzzi, Department of Pediatric Neurology and Psychiatry, Sapienza University of Rome

  • Barbara Tavazzi, Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome
  • Giuseppe Lazzarino, Division of Biochemistry and Molecular Biology, Department of. Biology, Geology and Environmental Sciences, University of Catania
  • Claudia Carducci, Department of Experimental Medicine, Sapienza University of Rome
  • Andrea Celato, Department of Pediatric Neurology and Psychiatry, Sapienza University of Rome
  • Federica Rachele Danti, Department of Pediatric Neurology and Psychiatry, Sapienza University of Rome
  • Maria Teresa Giannini, Department of Pediatric Neurology and Psychiatry, Sapienza University of Rome

Location of the trial: Department of Pediatric Neurology and Psychiatry, Umberto I Hospital, Rome, Italy
Sponsor: Umberto I Hospital, Rome, Italy
Funding: ELA Italy (patient support)

This study was designed as a fully open trial. Due to disease heterogeneity and variability of motor and functions impairment it is not feasible to apply a standardized protocol. Patients have been sub-grouped according to the stage of the progression of their disease and the type of their prevalent motor dysfunction. An intra-patient comparison, before and after pharmacological therapy, have been used to assess clinical effectiveness. No placebo, gender or stricted age limits will be taken into account due to mentioned reasons.

Experimental protocol
Neurotransmitters dysfunction in white matter disorders is still a controversial matter but the efficacy of L-DOPA, as described in some case studies, reminds to a supposed biogenic amines defect. This protocol ground on previous, single-patient, description of the effectiveness of L-DOPA in treating some target symptoms occurring in several forms of leukodystrophies and leukoencephalopathies. For instance some white matter disorders affected patients develop, during the course of their disease, akinetic patterns together with hypomimia, rigidity, dizziness, dystonia, slowness of movements, tremor, speech and swallowing dysturbances, dysautonomia, hyporesponsiveness to social and nonsocial stimuli or neurobehavioural problems and with signs of dopaminergic impairment. This could be, in some ways, connected to a parkinsonian-like pediatric phenotype. The main target of the present protocol has been the assessment of the effect of L-DOPA/carbidopa in improving the central motor deficits affecting patients with leukodystrophy.

Time table of the trial
Time 0: patient recruitment

Time 1: clinical and biochemical assessment

  1. Assessment of biogenic amines in urine
  2. Clinical assessment tools:
  • Vineland Adaptive Behavior Scale
  • Gross Motor Function Classification System (GMFCS)
  • International Cooperative Ataxia Rating Scale (ICARS)
  • Dyskinesia Impairment Scale (DIS)
  • Standardized video recordings

3.    Treatment protocol: L-DOPA/carbidopa administered starting from a dosage of 1 mg/kg/day for fifteen days and 5 mg/kg/day for the following 30 days. Domperidone will be considered in preventing gastrointestinal disorders in some cases.

Time 3: At day 45 the patient was again assessed according to the same clinical protocol

Time 4: In case of not satisfactory or absent clinical effect the dosage will be increased up to 10 mg/kg/day for a further month and then patients again re-assessed at the end of this period according to identical clinical protocol.


Inclusion criteria

  • Patient affected by primary leukodystrophies or leukoencephalopathies
  • Presence of disabling akinetic-rigid symptoms, hypokinesia, bradykinesia, hypomimia, rigidity, rest tremor, dystonia etc.
  • Age > 2 years

Exclusion criteria

  • Severe clinical impairment with no reasonable expectancy of motor improvement
  • Prevalence of spastic or peripheral deficits
  • Any impairment of general conditions (such as severe breathing and nutrition difficulties, vital parameters instability) that may make risky the trial

Preliminary results
To date ten patients (seven females and three males), with the age ranging from 3 to 16 years old, have been enrolled with the following diagnosis :

  • Alexander disease: 1 patient,
  • Pelizaeus-Merzbacher or Pelizaeus Merzbacher like disease: 2 patients,
  • Metachromatic leukodystrohy: 3 patients,
  • Vanishing white matter disease: 1 patient,
  • Krabbe disease: 1 patient,
  • Unclassified primary leukodystophies: 2 patients.

A slight improvement in social interaction and motor symptoms (bradykinesia improvement, an expansion in movement repertoires and motor fluency). Our preliminary data seems to support previous studies concerning a marginal but real role of L-DOPA in treating target movement disorders symptoms in white matter diseases.

Contact: Vincenzo Leuzzi, phone: +390644712282 / e-mail: