Neuronopathic Gaucher Disease in the USA


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Dr Raphael Schiffmann is specifically interested in the clinical and biochemical effects of enzyme replacement therapy on the systemic and neurological involvement in patients with Type 2 and Type 3 Gaucher disease. He is Chief of Clinical Investigations and Therapeutics Section in the Developmental and Metabolic Neurology Branch of the National Institute of Neurological Disorders and Stroke, USA. Dr Schiffmann spoke about his work at the US Gaucher Conference on 3 October 1999 in Arlington Virginia . Susan Lewis reports:


Patients with Types 2 and 3 make up 5% of the total Gauchers population,' explained Dr Schiffmann.

Type 2 Gaucher Disease

We have tried to treat Type 2 children aged between 10 months and 3 years. All received enzyme replacement therapy at a dose of 60-120 units per kilogram of bodyweight (u/kg/bw) every two weeks.

Three had to have a tracheotomy (where a tube is inserted into their throat because their vocal cords contract preventing them from breathing). Unfortunately they died before five years of age.

Our impression is that intravenous enzyme replacement therapy (into a peripheral vein) does not slow brain disease. The reason is because the enzyme does not cross the blood-brain barrier.

We have to improve the entry into the brain either by direct infusion into the brain or by using drugs that open the blood-brain barrier.

We hope to accomplish a trial to inject enzyme replacement therapy into the brain, by pumping the enzyme directly into the brain to get into the neurons (cells in the brain). However we first have to assess its safety and not whether the drug works.

It is not understood why it is bad for the brain to have a deficiency of glucocerebrosidase.

We are also interested in using inhibitors such as the new drug on trial called OGT 918. This drug has potential but needs to be proven in trials.

Type 3 Gaucher Disease

Most Type 3 children have difficulty moving their eyes from side to side. They also have severe systemic disease affecting their blood, liver, spleen and bones. They can have normal or reduced intelligence.

Some have mild systemic disease but develop seizures which presents in childhood or early adulthood.

We have cared for 20 Type 3 patients, eight female and 12 male aged from two to 35 years. Seventeen were under 15 years old. We have followed them on treatment from between two and eight years old. Two developed progressive myoclonic epilepsy.

Treatment for Type 3 Gaucher Disease

We have treated the Type 3 children with between 60 and 420 u/kg/bw every two weeks, depending on the effect to their systemic disease. If there was no systemic response, we raised the dose but the usual dose was 60 u/k/bw every two weeks. These patients require high enzyme therapy dose from the start.

The bones of the children improved after a few years. One child, a girl, was eight months when she started treatment. At eight years old, she has normal bones. Another child had compression of the vertebrae. The vertebrae showed improvement both in size and height of the child. In other children, rods inserted in their spine help straighten their back but this procedure stops growth in the back.

However there are areas where enzyme replacement therapy is less effective such as in the lungs.


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Source: Gaucher's News February 2000. © Copyright Gauchers Association 2000