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Beating the Blood Brain Barrier

Jamal Temsamani and Claude Laruelle of CLL Pharma go in search of a method that overcomes a formidable obstacle blocking the delivery of drugs to the brain

The prevalence of neurodegenerative diseases such as Parkinsonís disease, stroke, and Alzheimerís disease is increasing as the population ages. This, together with brain cancers, viral infections such as HIV, the threat of Creutzfeldt- Jakob disease and a broad range of psychophysical conditions, are putting increasing pressure on pharmaceutical companies to produce more effective drugs for brain disorders.

Brain diseases, however, are difficult to treat, not least because the brain is a highly complex and delicate organ, but also because it is inaccessible to many therapeutic molecules due to the blood brain barrier (BBB). It is estimated that this barrier prevents about 98 per cent of systemically delivered potential neurotherapeutics from entering the brain. Many novel drugs are under development, but to exploit new therapeutic approaches to the full, there is a compelling need for drug developers to find improved ways of overcoming the BBB.

THE NATURE OF THE BBB

The existence of the BBB was first suspected in the late 1800s, when it was noticed that water-soluble dyes injected into the blood stream did not stain the brain and spinal cord. The diffusion of a variety of molecules that readily distribute in many other organs simply does not occur at the BBB. Here, endothelial cells in the walls of blood vessels in the brain form a close-fitting monolayer connected by complex and largely impassably tight junctions (see Figure 1). Each brain capillary endothelial cell, in addition, is composed of two lipid membranes: the lumenal (facing the blood) and the ablumenal (facing the brain), which are separated by approximately 300nm of endothelial cytoplasm.


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Jamal Temsamani, PhD, joined CLL Pharma following the acquisition of Syntem. He has been the Vice President of Pre-Clinical Research and Development at Syntem since 1998. Jamal received his PhD in Molecular Biology from the University of Montpellier, France. After completing a post-doctoral fellowship at the Worcester Foundation for Biomedical Research, he joined Hybridon, Inc (MA, USA), where he served as Associate Director and Director of Discovery Group. In 1997, he was appointed Scientific Director of Hybridon Europe, where he was responsible for supervising and co-ordinating European collaborations. He has published more than 61 scientific articles and six book chapters and is co-inventor of 40 patents.

Claude Laruelle, PhD, is the Chief Executive Officer of CLL Pharma. Before founding CLL Pharma in 1995, he was CEO and R&D Director of Panmedica. He has held several other positions such as Vice President of pharmaceutical consulting firm Droit & Pharmacie and Research Engineer at Labaz-Sanofi. Claude holds a PhD in Physics and is a Chemical Engineer. He has developed 210 market authorisations for generics in Europe, is an inventor of 280 patents, and is the author of 27 scientific communications.

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Jamal Temsamani
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Claude Laruelle
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