A Letter from The Office of the Vice Chancellor for Research

OVCR Annual ReportFiscal Year 2011Technology Management & Intellectual PropertyMethod of Treating PruritusItch, or pruritus, is an unpleasant sensation that causes the desire to scratch, associated withmany conditions such as liver disease or kidney dialysis, can find no relief for the problem.Pruritus is also a serious condition experienced by animals. The present invention providesmethods for treating pruritus by providing methods of substantially inhibiting the activation ofbombesin receptors or by killing GRPR specific neurons in the spinal cord. Mitigation of itchthrough either of these mechanisms does not affect motor or sensory functions. PrimaryInvestigator: Zhou-Feng Chen, Anesthesiology.Novel Genetic Risk Factor for Alzheimer’s Disease ProgressionResearchers at Washington University have identified a novel genetic variant that stronglycorrelates with Alzheimer’s disease progression. Dr. Alison Goate and collaborators used anestablished biomarker for the decline of AD patients (cerebrospinal fluid tau phosphorylated atthreonine 181, ptau 181 ) to find genetic variants that influence levels of ptau 181 in the cerebrospinalfluid. The study found a highly significant association between ptau 181 levels and the rs1868402SNP located within a regulatory subunit of PPP3R1 (calcineurin B), a gene previously linked toAD pathogenesis. Carriers of the rs1868402 risk allele showed a 6-fold faster rate of diseaseprogression than AD patients without the variant. Direct examination of brain samples fromAD cases and controls revealed that rs1868402is in fact associated with reduced PPP3R1 mRNAlevels and increased tangle formation, providing biological validation for the genome-wideassociation study and further implicating PPP3R1 in disease pathology. As the first geneticvariant associated with rate of AD progression to be reported, its use in clinical trial design andpatient care will translate into a significant benefit to patients. Primary Investigator: AlisonGoate, PsychiatryBlood A Production and Clearance Measurements as a Diagnostic Test forAmyloidosis and Alzheimer's DiseasePrevious work from the Bateman and Holtzman labs have demonstrated clinical utility inmeasuring the synthesis and clearance rates of the amyloid-beta (Aβ) protein as a biomarker forefficacy of candidate Alzheimer’s drugs that target the protein. In a completely distinctinvention, the labs have demonstrated the ability to detect changes in Aβ in blood plasma, anassay that has utility for assessing drug candidates as well as diagnostic applications. PrimaryInvestigator: Randy Bateman, Neurology, and Dave Holtzman, NeurologyNovel Antithrombin Nanoceutical for Preventing Blood ClotsThe current invention comprises a first-in-class nanoparticulate antithrombotic that features apotent dual antithrombin/antiplatelet compound linked to a nanoparticle to function as a singleunit or drug. Advantages of this novel agent include (1) prolonged activity of drug at thenanoparticle surface and only at the site of active clotting, (2) potential for image-baseddetection and tracking of the agent and the acute thrombotic process, (3) the elimination ofharmful side effects after systemic delivery through the use of smaller drug amounts featuringsite-specific thrombin targeting and action, (4) well defined pharmacokinetics that are driven bythe nanoparticle itself and are independent of a subject’s genetics, and (5) the ability to multiplex anyother anticoagulant that is already on the market or in development for combination44