Blood-Brain Barrier Carriers – the Next Frontier for CNS Diseases?

1283464811 24 Blood Brain Barrier Carriers the Next Frontier for CNS Diseases?

A successful way to move drugs across the blood-brain barrier is essential for treatment of Alzheimer’s and other CNS diseases.
Alzheimer’s disease, the most common form of dementia, affects many biological systems throughout the brain and body. New effective treatments for Alzheimer’s disease are badly needed, and many different drug classes have been investigated as potential therapies. However, all Alzheimer’s disease treatment strategies face one major limitation: the blood-brain barrier, a capillary network sealed in specialized endothelial cells that prevents most molecules from passing from the bloodstream to the brain.

The blood-brain barrier is well adapted to protect the brain from infection and toxicity, with sensitive mechanisms to transport essential molecules into the central nervous system and pump potentially harmful molecules out. These systems also prevent drugs from reaching central nervous system targets. The FDA has approved members of two drug classes, cholinesterase inhibitors and NMDA receptor antagonists, to improve Alzheimer’s disease patients’ cognitive symptoms. Both types of drug work by increasing the levels of important brain signaling molecules (acetylcholine and glutamate, respectively) in brain areas where cells are most severely affected by Alzheimer’s disease. However, like treatments for Parkinson’s disease, epilepsy, and brain tumors, these and future Alzheimer’s disease drugs must enter the brain to be effective.

The sophistication of the human blood-brain barrier is one of the reasons that many potential Alzheimer’s disease treatments that show promise in animal models are not effective in human clinical trials. If Alzheimer’s disease drugs can enter the brain at all, it is often at only a fraction of their original dose. Existing Alzheimer’s disease drugs could also be more effective if they could enter the central nervous system more efficiently. After years of neglect, the blood-brain barrier has become the focus of renewed interest, with applications for Alzheimer’s disease and other CNS diseases at the forefront of research.

Several different strategies have been adopted to move Alzheimer’s (and other CNS) disease drugs across the blood-brain barrier. Fats are known to cross the blood-brain barrier, but altering drugs into fat-soluble forms often reduces their effectiveness. Some drugs, such as anti-convulsants to treat epilepsy, can utilize the body’s system for transporting large, neutral amino acids across the blood-brain barrier, but the chemical structure of most Alzheimer’s disease drugs makes them unsuitable for this. Treatments that temporarily “open” the blood-brain barrier to a greater range of substances can be difficult to time correctly. Other investigations have focused on inhibiting or evading the brain’s system to remove toxic substances, maximizing the effectiveness of an Alzheimer’s disease drug once it enters the brain.

Some of the most promising developments in central nervous system drug delivery to date have been the result of exploiting molecules, such as nanoparticles and specific proteins, which can easily cross the blood-brain barrier. These molecules can be used as carriers for pharmaceuticals that could not normally enter the brain. BiOasis is currently developing its patented Transcend (TM) technology, which uses the p97 protein as a carrier molecule, for the delivery of pharmaceuticals to the brain. This type of technology could be particularly beneficial to Alzheimer’s disease drug development, because it can be applied to a wide variety of drug classes. Once the blood-brain barrier can be reliably traversed, many more potential CNS disease treatments may prove effective.

Technorati Tags: Alzheimer’s Disease, Alzheimer’s Drugs, BioAsis, Blood Brain Barrier, P97, Transcend