Drug Discovery Opinion

The blood-brain barrier (BBB) fulfills an essential role by restricting the entry of potentially neurotoxic chemicals into brain tissue. The downside of this protective function is that entry of therapeutic molecules into the brain may also be severely restricted; delivering adequate amounts of drugs is one of the biggest challenges in treating many brain diseases.

L-Dopa, used to treat Parkinson’s Disease, is transported into the brain using a carrier system (LAT 1) which normally transports large neutral amino acids. L-Dopa is close enough in structure to one of the endogenous substrates, phenylalanine, to gain entry using this transporter, but the constraints in terms of size and shape on the transported molecule mean that opportunities for such carrier-mediated transport are very limited.

Now Armagen Technologies has announced funding by the Michael J. Fox Foundation for Parkinson’s Research to develop a receptor-mediated system to deliver a neurotrophin into the brain. Receptor-mediated transport mechanisms involve attaching the drug molecule to a protein recognized by cell surface receptors and triggering an energy-dependant transcytosis. In this case, the neurotrophin, which protects the part of the brain that degenerates in Parkinson’s Disease, is fused to a monoclonal antibody which is able to cross the blood brain barrier and so deliver the neurotrophin into the brain tissue.

Receptor-mediated transport mechanisms offer greater flexibility in terms of the size and shape of drug molecules that can be transported, and are likely to be more widely applicable than carrier-mediated systems.

Bookmark It

Hide Sites

Related posts:

1. Statins Protect Mice from Symptoms of Parkinson’s Disease Statins lower cholesterol by inhibiting HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis, and new indications have continued to emerge...
2. P-Glycoprotein – A Close-up View P-glycoprotein (Pgp), with its ability to transport a wide range of xenobiotic compounds – including drug molecules – across cell...
3. E3 Ubiquitin Ligase CHIP Regulates LRRK2 Stability Although mutations in the gene for leucine-rich repeat kinase 2 (LRRK2) have been linked to both familial and sporadic cases...
4. Yeast Cells: Drug Discovery Factories Whitehead Institute researchers have described a new drug discovery technique which uses yeast cells to both synthesise and screen novel...
5. Neuroprotective Small Molecule TrkB Agonist Roles have been suggested for brain-derived neurotrophic factor (BDNF) – which helps to support neurons and also stimulates and controls...

Related posts brought to you by Yet Another Related Posts Plugin.

 Email This Post

This entry was posted on Monday, September 1st, 2008 at 8:36 am and is filed under News. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.