Blood-Brain Barrier: A Closer Look On How It Works

The BBB is to protecting the brain internally as the skull is to protecting it externally. The problem is the BBB does not differentiate what it keeps out. Life-saving chemicals, if they happen to be the wrong chemicals, simply won't get through. With very few exceptions, only small molecules soluble in fat clear the barrier. Only two percent of small-molecules get through. These include alcohol, caffeine, and nicotine.

Small-molecule compounds have been used to treat affective disorders, schizophrenia, chronic pain, and epilepsy, but they leave a lot to be desired. The problem, says William Pardridge MD of UCLA writing in the Jan 2003 Archives of Neurology, is that "small molecules are largely palliative medicines with often unfavorable safety profiles."

Dopamine is one of those types of small molecules, but unfortunately, their chemical structure stops them from passing the BBB. However, L-DOPA can follow a certain type of amino acid transporter through the BBB without even knowing it.

Dr. Pardridge and his team have been experimenting on encasing genes in liposomes coated with what they called a special polymer in order to attach them with antibodies. Why antibodies? The antibodies are the ones that sneak their way pass the brain-capillary receptors so the liposomes could complete their mission. In one of their experiments, they injected rats that had Parkinson’s with liposomes containing a gene that “boosts production of the enzyme tyrosine hydroxylase,” (a building block of dopamine). The rats’ abnormal symptoms were then reduced up to 70% three days later. By completing multiple experiments with the same procedures, rats with brain tumors doubled their lifespans. With weekly injections, delivery of antisense RNA that blocked production of a malignant growth factor was a success.

What’s the point in finding the cure to a neurological disease, if there is a high possibility that it won’t even make it pass through the BBB  in order to receive the full effect?  Since there is no academic neuroscience program that focuses on BBB transport biology or drug targeting, who knows how long it would take for it to become funded with the technology and research.  For example, if someone is trying to sell you a product that is 99% effective, wouldn’t you feel more confident if it had that one last percent? But once again, the Blood-Brain Barrier only has a two percent chance for the medication to become in full-effect. So would you take that risk? These are the kind of things that makes you wonder.