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Letters to the Editor
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Blood-brain barrier
Challenges facing CNS drug discovery and development
From Dr M. S. Alavijeh
My wife, who is a pharmacist, highlighted to me the article “Crossing
the blood-brain barrier: drug delivery to the brain is still elusive” (PJ,
2 October, p475). I read with much interest the article and certainly it
is true that, as oppose to drugs targeted for systemic therapy, drugs designed
as brain medicine must pass the blood-brain barrier (BBB) through the mechanisms
indicated in the article.
Central nervous system (CNS) disorders are major causes of mortality and
disability and are predicted to become the major medical need of the 21st
century. This is because the incidence of many CNS disorders increases
exponentially after age 65 and the number of people in the world over 65
is about to increase sharply because of a marked rise in fertility after
the 1939–45 war. The cost of getting a drug to market has been estimated
to be $1bn — it is probably more for CNS drugs, which take longer
to get to market (12–15 years) than non-CNS drugs (10–12 years).
What is more, the success rate for CNS drug candidates is considerably
lower than that for non-CNS drug candidates.
We are still far from fully understanding the complexity of the brain.
Despite many decades of effort, our progress in developing new therapies
for CNS disorders has been somewhat disappointing and unsatisfactory. A
limited understanding of disease mechanisms and how existing treatments
work has impeded discovery of more effective therapies. Indeed, a new drug
discovery paradigm, based on defined molecular mechanisms and understanding
disease, will be necessary for the development of completely new therapies.
Breakthroughs in genetics, along with approaches such as transcript profiling,
proteomics and systems biology, can be anticipated. This, coupled with
an increased appreciation and assessment of brain penetration and the liability
of compounds to cause CNS side effects will contribute to the more efficient
and effective provision of safe and effective medicines for CNS disorders.
It remains to be seen whether this is sufficient to meet the needs of the
epidemic of age-associated disorders of the brain that is about to hit
the world.
Mohammad S. Alavijeh
Chief Scientific Officer
Pharmidex |
The
Pharmaceutical Journal