1、CNS Drug Delivery: Beyond the Spinal CordMission: Improve outcomes for epileptic patients who dont respond to conventional treatments by administering reformulated, micro-doses of anti-epileptic drugs directly to the brain.Daniel J. Abrams, MD December 2012 This presentation includes the description
2、 of drugs, devices and their therapeutic uses that are in early stages of development, are not commercially available and have not been approved by regulatory institutions. Before commercialization is possible the drugs, devices and their therapeutic uses need to undergo additional preclinical and c
3、linical evaluation and obtain regulatory approval. Disclaimer on Product UseSignificant Unmet Medical Need for Neurological Disorders and Disease Large # of Indications Growing patient populations Few effective therapies Enormous cost of care 15M US PatientsEpilepsyU.S. Epilepsy MarketTotal Patients
4、 1.0% or 3 million1Refractory Patients 1,000,0002Most Severe Refractory Patients 600,000Refractory Epilepsy Treatment Market $2.5 billionAntiepileptic Drug Market (World, 2008) $11.34 billionImplantable Pump Market- Pain & spasticity applications10,000 units,$600 million1http:/www.epilepsyfoundation
5、.org/aboutepilepsy/whatisepilepsy/statistics.cfm2http:/ Blood Brain Barrier excludes most drugs from Brain and Spinal Cord . . . . . despite most dense vascular bed of any organ.*radioactively labeled tracer drug given intravenouslyGabapentin, smallmolecule (0.2kD)Prialt, peptide(3kD)siRNA(13kD)prot
6、ein antibody(150kD)Drugs keep getting bigger:Factors Frustrating CNS Drug TherapyPeripheral Capillary Brain Capillarypermeability restricted to: small molecules (600D) lipophilic substancesProteinGlucoseSelectivity of the Blood Brain BarrierAnatomy of the Blood Brain BarrierElectron Micrograph ofTig
7、ht JunctionsCrossing the Blood Brain Barrier1. betweenpermeabilize tight junctions3. arounddirect intracranial drug delivery2. throughenhance transport acrossthe endothelium19801982198819901991199219962000200420102012First human implant of SynchroMed pump (Medtronic)SynchroMed pump receives FDA appr
8、oval (Medtronic)Infumorph (IT morphine) approved (Medtronic)Lioresal (IT baclofen) approved for spasticity (Medtronic)MedStream (constant flow) pump approved (Codman JnJ)SynchroMed II pump receives FDA approval (Medtronic)Prialt (IT Ziconitide) approved for chronic pain (Azur)Gablofen (IT baclofen)
9、approved for spasticity (CNS Therapeutics)Prometra Programmable Pump approved for IT pain (Flowonix)MedStream Programmable Pump System approved for IT spasticity (Codman JnJ)IT Therapy Development History(Selected Highlights)Several Infusion Systems Availablefor Targeted Drug DeliveryMEDSTREAM Programmable Infusion Pump and Control UnitSynchroMed II Infusion Pump & Nvision Clinical ProgrammerPrometra Pump and Programmer
