Pharmidex Pharmaceutical Services - Blood Brain Barrier Permeability Assessment

Headquartered in London, Pharmidex focuses on the prediction and assessment of the ability of potential new medicines to cross the permeability barrier between blood and brain – the Blood-Brain Barrier (BBB).

As world-leaders in this area, our offerings (Clarity™ , Penetrability™ and NeuroPK®) add value by accelerating time to market and improving the probability of success. This is achieved through a number of biological screens, coupled with our in silico technology to effectively predict BBB permeation.

Our offering can also be used by non-Central Nervous System (CNS) drug discovery projects that need to establish that their lead compounds do not cross the BBB and thus have a liability to cause CNS side-effects.

In collaboration with Genzyme Pharmaceuticals, we also offer CERENSESM - a breakthrough in the delivery and assessment of new CNS medicines. It can help realise the full value of all potential CNS medicines whose utility is constrained by poor BBB permeation.

PREDICTING BRAIN PERMEATION

Clarity™ is our proprietary in silico technology to predict the ability of compounds to cross the blood-brain barrier. Unlike other models available, it is informed on the basis of consistent data measuring brain penetration.

This screen allows libraries of virtual or actual compounds to be segmented on the basis of brain penetration, which serves to both reduce development time and increase the probability of success. We have established a strategic alliance with Strand Life Sciences - a premier in silico technology innovation company.

BLOOD-BRAIN BARRIER PERMEATION ASSESSMENT

We offer a variety of approaches to assess the ability of compounds to permeate the BBB.

Penetrability™ provides an in vitro assessment of the ability of compounds to cross the blood-brain barrier using Madine-Darby Canine Kidney (MDCK) II cells engineered to overexpress P-glycoprotein (P-gp). Like the intact BBB, MDCK cells have tight junctions and a high transmembrane resistance. It therefore provides a good model to assess passive diffusion across the BBB, which effectively and reliably predicts brain penetration in vivo. This, along with the ability to also assess P-gp transport, makes Penetrability™ a very useful model of BBB function in CNS drug discovery.

In situ brain perfusion measures the rate of entry across brain endothelium. It therefore represents a kinetic measure and is superior to measures of brain partition, such as determination of brain/plasma ratio.

NeuroPK® provides an assessment of the ability of compounds to penetrate into the brain substance and remain there long enough and at a sufficient concentration to exert the desired action at its target molecule. Brain interstitial fluid is the key compartment for a CNS active drug. NeuroPK® measures the concentration of a compound in this compartment over time, which permits calculation of Cmax, half-life and AUC. In addition to monitoring free drug concentration, we will also determine the concentration of test compound in whole brain, CSF and blood.

NeuroPK® will thus deliver a comprehensive assessment of the concentration and duration of a test compound in the interstitial fluid of a distinct brain region, in ventricular CSF as well as blood. These studies can be conducted at the discovery and preclinical phases using both rodent and non-rodent species. We can also conduct neuropharmacodynamic studies at the same time, which will permit relationships to be established between neuropharmacokinetic (PK) and neuropharmacodynamic (PD) data. These approaches can add real value to CNS drug discovery projects by both accelerating time to market and improving the probability of success. They can also be used by non-CNS projects that need to establish that their test compounds do not cross the BBB and thus have a liability to cause CNS side-effects.

DELIVERING COMPOUNDS ACROSS THE BBB

CERENSESM is a unique product development platform designed to substantially improve the development success of CNS medicines that normally exhibit poor permeation of the barrier that exists between the blood and brain (the BBB), and open potential new avenues for CNS medicines research.

CERENSESM is available exclusively from a newly formed partnership between Genzyme Pharmaceuticals and Pharmidex Pharmaceutical Services. The CERENSE product development platform can be reviewed at your company under confidentiality and a customised program of study tailored to your specific drug therapy needs. Drug compounds are assessed under a product collaboration agreement that is exclusive for the duration of your study.