Neuronopathic Gauchers Disease


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Neuronopathic Gauchers disease (Types 2 and 3) was discussed at two overseas meetings: the European Working Group for Gauchers Disease in Jerusalem on 6-9 September 2000 and at the National Gaucher Foundation Conference held in Arlington, Virginia on 12-13 November 2000.


Dr Raphael Schiffman, based at the National Institutes of Health, Bethesda, USA said at the National Gaucher Foundation Conference in November 2000 that neuronopathic Gauchers disease accounts for 5% of the total Gauchers population.

He described the symptoms and signs of this type of Gauchers disease ranging from problems with eye movement, severe blood and bone disease in most cases, to progressive neurological involvement causing eventual death in Type 2.

He pointed out that some patients with neuronopathic Gauchers disease (Type 3) have become stable when on sufficient doses of enzyme replacement therapy but said that even slightly affected sufferers of neuronopathic Gauchers disease will have some quality of life impairment. For instance they could not learn to drive a car.

Dr Schiffman said that Type 3 children on enzyme replacement therapy have achieved considerable bone increase in the cortical thickness of their legs and hips while their haematological (blood) problems and organ size decreased significantly.

The majority of sufferers have lung problems which enzyme therapy was not helping and in his experience there is no evidence that eye movement or cognitive ability has improved.

There therefore needs to be additional treatment approaches. OGT918 is theoretically promising but may have possible side effects. He and Dr Roscoe Brady plan to initiate a trial with OGT 918 in the near future on children with neuronopathic Gauchers disease.

Type 2 Gauchers Disease

Dr Roscoe Brady said that he, Dr Schiffman and his team are re-searching into the possibility of getting enzyme replacement therapy into the brain of sufferers of Type 2 Gauchers disease. He said that all previous attempts to get the enzyme into the brain had failed. Their aim is to insert a small catheter (tube) into the base of the brain and inject glucocerebro-sidase into it under slight pressure.

He discovered in tests on rats that when the enzyme is pumped into the brain in this way it is reasonably stable and is not toxic. The enzyme moves to the cortex (area) of the brain where the neurons (cells involved in nerve function) are damaged. Fortunately the neurons specifically took up the enzyme so no further targeting to these cells is necessary.

Dr Schiffman said this work is experimental. He pointed out that the same area of brain in a Gauchers Type 1 patient with Parkinson's symptoms, was affected as the area of brain in children with neuronopathic disease. The greater the area of brain affected, the more severe the symptoms.

Type 3 Gauchers Disease

Dr Gheona Altarescu, who formerly worked at the National Institutes of Health (NIH), USA and is now based at the Shaare-Zedek Medical Centre in Israel, spoke about enzyme replace-ment therapy in patients with Type 3, at the EWGGD meeting in September . While at NIH, she studied 21 Type 3 Gauchers disease patients, aged 8 months to 37 years. Their enzyme dose was adjusted to control manifestations in the blood, liver, spleen and bone. The patients were evaluated at the start and every 6 to 12 months thereafter. They were followed for 2 to 8 years.

Significant improvement of haemoglobin levels, platelet count and acid phosphatase occurred. Liver and spleen volume decreased and bone structure improved. Nineteen patients had lung disease which did not show symptoms but was unresponsive to enzyme replacement therapy.

Supranuclear gaze palsy (eye abnormality) remained stable in 19 patients, worsened in one and improved in one. Cognitive function remained unchanged or improved over time in 18 patients but decreased in three patients who developed a pro-gressive form of epilepsy. Cranial MRI and EEG were normal in 18 patients but deteriorated in the three patients who developed epilepsy. At relatively high doses (60 to 240 units/kilogram/bodyweight every two weeks, enzyme therapy reverses almost all systemic manifestations in patients with Type 3 disease and most treated patients do not deteriorate neurologically. Only one patient was on the very high dose.


Neuronopathic Gaucher's News Contents
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Source: Gauchers News March 2001.
© Copyright Gauchers Association 2001