A clinical trial: the role of L-DOPA in the treatment of movement disorders in patients suffering from leukodystrophy

Written on Thursday 5 June 2014

At the instigation of ELA Italy and its president Silvano Vona, a clinical trial to test the effects of L-DOPA on patients suffering from leukodystrophies is currently underway in Italy. This trial is based on results observed for Edoardo, Mr Vona’s son, who suffers from metachromatic leukodystrophy. In contrast to the clinical trials generally proposed to patients suffering from leukodystrophy, this procedure is for patients with declared disease symptoms.

L-DOPA, or levodopa, is a dopamine precursor used in the treatment of Parkinson disease. In the brain, dopamine fonctions as a neurotransmitter, i.e. a molecule responsible for transmitting signals between neurons.

What does it consist of?

The aim of this study consists of evaluating the efficiency of L-DOPA to act at the level of rigidity and akinesia occurring in a certain number of leukodystrophies. This akinesia, i.e. difficulty or  impossibility to initiate voluntary movements seen in patients suffering from leukodystrophies, could be linked to parkinsonian-like symptoms, but which are specific to the child.

The trial, directed by Pr. Vincenzo Leuzzi, has been carried out at the Umberto I hospital of Rome (Italy) since last July and is scheduled to run for one year. The medical team involved in the study is composed of Pr. Barbara Tavazzi (Biochemistry and Clinical Biochemistry Institute, Catholic University of Rome) and Drs. Giuseppe Lazzarino (Biochemistry and Molecular Biology Division, Catane University), Claudia Carducci (Department of Experimental Medecine, Sapienza University of Rome), Andrea Celato, Federica Rachele Danti and Maria Teresa Giannini (Department of Pediatric Neurology and of Psychiatry, Sapienza University of Rome).


Given the heterogeneity of leukodystrophies and the variability of motor disorders, the patients were divided into sub-groups based on the stage of their disease and their principal motor damage.

All patients, boys and girls, irrespective of age, received L-DOPA treatment, associated with carbidopa to prevent premature L-DOPA degradation in the body.

The L-DOPA/carbidopa treatment was initially at the dose of 1 mg per kilogram per day for 15 days, then was continued at a dose of 5 mg per kilogram per day for the following 30 days. If necessary, domperidone was prescribed to prevent gastro-intestinal disorders.

Different examinations were carried out before and after treatment, such as urine analysis, evaluation of motor function and behaviour of the patients.

In the absence of a satisfactory clinical effect after 45 days of therapy, the treatment will be changed to 10 mg per kilogram per day for a further month, at the end of which time the patients will be evaluated again.

Follow-up of patients and preliminary results

To take part in this trial, the patients suffering from a leukodystrophy or a leukoencephalopathy, aged above 2 years old, must show signs of akinesia and handicapping rigidity. If the patients had motor defects without the possibility of improvement, or problems of respiration and nutrition, they could not be included in the study.

From a practical point of view, ELA Italy gives financial support to the families whose children take part in the trial, for example by paying their board and lodging during the hospitalization of their child.

To date, ten patients (seven girls and three boys) aged between 3 and 16 years old have taken part in this study. They suffer from Alexander disease (one patient), Pelizaeus-Merzbacher disease or Pelizaeus-Merzbacher-like disease (two patients), metachromatic leukodystrophy (three patients), CACH syndrome (one patient), Krabbe disease (one patient) and indeterminate leukodystrophies (two patients).

A slight improvement concerning the social interaction of the patients and their motor defects was observed. These preliminary results underline the result of anterior studies describing a marginal but real role of L-DOPA in the treatment of movement disorders in diseases of the white matter.

For more information about this clinical trial, please contact Pr. Vincenzo Leuzzi by telephone on +390644712282 or by email at vincenzo.leuzzi@uniroma1.it

A new L-DOPA clinical trial: the explanations of Pr. Leuzzi

“Our aim is to evaluate the effect of levodopa/carbidopa on different forms of leukodystrophies accompanied by problems of rigidity and akinesia. This drug is generally used to treat advanced parkinsonian syndromes.

Levodopa is a precursor of dopamine, a major neurotransmitter in the brain that is implicated in the modulation of motor functions. At low doses, levodopa/carbidopa is well-tolerated both in adults and children. Some intestinal discomfort can occur and gastro-esophageal reflux may be aggravated in certain cases.
For this first clinical trial, we envisaged the recruitment of approximately ten patients on the basis of their movement disorder. This led to the selection of different forms of leukodystrophies.  We evaluated the patients’ clinical status and their movement defects before and after treatment, but we also measured the blood and urinary dopamine concentration and the occurrence of undesirable side-effects.

The most frequently observed improvements concern the attention span and hypokinesia, or the reduced capacity for movement. We hope to be able to show a clinical improvement that is inversely proportional to the disease severity in these patients. We are also in the process of exploring the time-span of the therapeutic effect. Effectively, in certain patients, the beneficial effect disappears after several days or several weeks.”

To find out more: the details of the clinical trial