Neurological, psychiatric, malignancies, infections and other diseases affecting the central nervous system (CNS) are already major pharmaceutical markets. And a recent paper in Drug Discovery Today remarks that drugs acting on the CNS represent the pharma industry’s “largest potential growth sector.” For example, the biotechnology company Allon Therapeutics suggests that sales for Alzheimer’s medicines should exceed $7.8 billion by 2010 in the seven major markets. It adds that the stroke market could reach $415 million by the same time.

Nevertheless, the blood-brain barrier (BBB) poses a formidable obstacle to on-going commercial, scientific and clinical success in CNS therapeutics. Writing in Drug Discovery Today, Pardridge comments that the BBB blocks essentially all large molecules (such as proteins and antibodies) and more than 98% of small molecules from reaching the CNS.

Circumnavigating the BBB

Not surprisingly, numerous academic, biotech and big pharma projects are trying to find ways around the BBB. According to Daniel Alkon, scientific director of Blanchette Rockefeller Neurosciences Institute (BRNI), West Virginia, some previous carriers including viruses and artificial polymers, delivered their payload across the BBB. However, these carriers “posed high levels of risk.” Other carriers, such as liposomes, often proved unstable or released their cargo in the liver, the lining of blood vessels and other unwanted locations.

Last week, however, BRNI researchers announced that they have patented a new mechanism of transporting medicines across the BBB. The system prevents the carrier from releasing its cargo until it reaches the BBB.

The new approach exploits a facet of the BBB’s natural physiology. The BBB uses a process called transcytosis to transport essential nutrients and other molecules, such as cholesterol, into the brain. The membrane on the blood side creates a ‘sac’ or vesicle around the molecule. This passes through the layer of cells that forms the BBB and releases the molecule into the CNS. In some cases, a specific receptor controls transcytosis.

A 'powerful' new tool

The method patented by BRNI uses low-density lipoproteins (LDLs), which normally carry cholesterol from the liver to the brain and other tissues. BRNI researchers coated the particles with apolipoprotein E, a naturally occurring protein, which attaches the particles to specific receptors expressed by cells that form the BBB. These receptors assist the particle across the barrier into the brain. The drug, contained in the particle’s central lipid core, hitches a ride across the BBB. Scientists at BRNI used the approach to deliver a variety of test substances into rats’ brains with, they say, no ill effects.

“This may lead to a powerful new tool that clinicians can use to treat brain diseases,” Dr Alkon said. “The blood-brain barrier provides effective protection to the brain against circulating toxins, bacteria and other harmful substances. But we need to have an effective means of delivering drugs across the barrier if we are going to offer patients better treatment options.”