The Blood-Brain Barrier

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Dr David Begley is Co-Director of the Blood-Brain Barrier Research Group at Kings College London and has researched this subject since 1980. He spoke about the importance of the blood-brain barrier with regard to neuronopathic Gaucher Disease at the European Family Conference in November 2004.

The brain is a very special organ. It is of course the organ that makes us who we are and is where the person and personality resides.

Because nerve cells in the brain communicate with each other by chemical messages, the brain requires a very stable background against which these chemical messages can be sent from nerve to nerve. The composition of the fluid in the brain must be kept constant so that nerve cells can maintain a controlled electrical resting potential. Otherwise the background noise against which the nerve cells would have to communicate would become excessive and messages would become scrambled. Just like having a conversation at a noisy party.

The composition of the fluid in the body which bathes our cells is variable and changes when we eat, exercise or become excited. Thus the brain requires a buffer between itself and the body in general. This is the blood-brain barrier.

A protective barrier

The blood-brain barrier is created by the cells which line the small blood vessels (capillaries) of the brain, called endothelial cells. These cells form tight junctions between each other which are not generally present in most organs and stop a free exchange of substances occurring between the blood and the brain. This barrier protects the brain and creates its unique environment.

Hence, the brain requires special transporters to enable nutrients which it needs, such as glucose, to cross the barrier from the blood into the brain.

The presence of the blood brain barrier means that many drugs which are intended to treat central nervous disease have difficulty getting into the brain in the necessary quantity to be effective. This applies to conditions such as brain tumours, Parkinson's disease, Alzheimer's disease, epilepsy, malaria, HIV, meningitis and of course neuronopathic lysosomal storage diseases.

Many of the lysosomal storage diseases, including Gaucher Disease, have neuronopathic consequences. The lack of sufficient enzyme which creates the disease is also lacking in the lysosomes of the brain cells.


Evidence is growing that the blood-brain barrier itself may also become damaged in some lysosomal storage diseases thus contributing to the neurological symptoms, in addition to the problems directly caused by the accumulation of storage products in brain cells. Because of the presence of the blood-brain barrier the enzyme replacement therapies now in use to treat a number of lysosomal storage diseases do not reach the brain cells.

As life expectancy increases as a result of the current treatments in use, so the incidence of some of the neuronopathic problems may become more evident. Clearly the development of effective strategies for directing therapeutic compounds and enzymes through the blood-brain barrier in order to reach and treat the brain is essential and urgent.

Ways to pass through the barrier

Ways need to be found to enable drugs to pass through the blood-brain barrier and remain active and effective in the brain. This can possibly be done by, either tailoring the biochemical shape or form of the drug to allow it to pass through the blood-brain barrier passively or by using the natural nutrient transporters, or by developing complex molecular envelopes like Trojan Horses which sneak large packages of drug through the blood-brain barrier and avoid its defences. This latter system may well be required to deliver large molecules such as replacement enzyme into the brain.

Neuronopathic Gaucher's News Contents
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Source: Gauchers News May 2005.
Copyright © Gauchers Association 2005.