Ohio History Spring 2016

https://kent-islandora.s3.us-east-2.amazonaws.com/node/10126/OH-v123n1-thumb.jpgOHIO HISTORY Contents for Volume 123, Number 1, Spring 2016 Contributors ...... 4 Editor’s Note ...... 5 &nbsp; Love and Danger on the Underground Railroad: George and Edy Duncan’s Journey to Freedom, 1820 Roy E. Finkenbine&nbsp;...... 7 From Places Between to Industrialized Countryside: Creating Enriched Uranium and Coal-Fired Energy in the Ohio Valley in the Early Cold War Era, 1952–65 Megan Chew ...... 26 President William T. Jerome III: Why Bowling Green State University Remained Open after the Kent State Shootings Joshua Casmir Catalano ...... 51 The Wright Brothers’ Early Photography: A Research Note Casey Huegel ...... 73 Exhibit Review: The John P. Parker House, Ripley, Ohio ...... 88 &nbsp; Book Reviews ...... 91 On the cover: Daniel Henderson, a young neighbor of the Wright brothers, poses with arms crossed outside the Wright family home at 7 Hawthorn Street, Dayton, 1899‒1901. (Source: Library of Congress, Prints and Photographs Division, LC-W85-28)</p

A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer’s disease

Introduction: Despite significant progress, a disease-modifying therapy for Alzheimer’s disease (AD) has not yet been developed. Recent findings implicate soluble oligomeric amyloid beta as the most relevant protein conformation in AD pathogenesis. We recently described a signaling cascade whereby oligomeric amyloid beta binds to cellular prion protein on the neuronal cell surface, activating intracellular Fyn kinase to mediate synaptotoxicity. Fyn kinase has been implicated in AD pathophysiology both in in vitro models and in human subjects, and is a promising new therapeutic target for AD. Herein, we present a Phase Ib trial of the repurposed investigational drug AZD0530, a Src family kinase inhibitor specific for Fyn and Src kinase, for the treatment of patients with mild-to-moderate AD. Methods: The study was a 4-week Phase Ib multiple ascending dose, randomized, double-blind, placebo-controlled trial of AZD0530 in AD patients with Mini-Mental State Examination (MMSE) scores ranging from 16 to 26. A total of 24 subjects were recruited in three sequential groups, with each randomized to receive oral AZD0530 at doses of 50 mg, 100 mg, 125 mg, or placebo daily for 4 weeks. The drug:placebo ratio was 3:1. Primary endpoints were safety, tolerability, and cerebrospinal fluid (CSF) penetration of AZD0530. Secondary endpoints included changes in clinical efficacy measures (Alzheimer’s Disease Assessment Scale – cognitive subscale, MMSE, Alzheimer’s Disease Cooperative Study – Activities of Daily Living Inventory, Neuropsychiatric Inventory, and Clinical Dementia Rating Scale – Sum of Boxes) and regional cerebral glucose metabolism measured by fluorodeoxyglucose positron emission tomography. Results: AZD0530 was generally safe and well tolerated across doses. One subject receiving 125 mg of AZD0530 was discontinued from the study due to the development of congestive heart failure and atypical pneumonia, which were considered possibly related to the study drug. Plasma/CSF ratio of AZD0530 was 0.4. The 100 mg and 125 mg doses achieved CSF drug levels corresponding to brain levels that rescued memory deficits in transgenic mouse models. One-month treatment with AZD0530 had no significant effect on clinical efficacy measures or regional cerebral glucose metabolism. Conclusions: AZD0530 is reasonably safe and well tolerated in patients with mild-to-moderate AD, achieving substantial central nervous system penetration with oral dosing at 100–125 mg. Targeting Fyn kinase may be a promising therapeutic approach in AD, and a larger Phase IIa clinical trial of AZD0530 for the treatment of patients with AD has recently launched. Trial registration: ClinicalTrials.gov: NCT01864655. Registered 12 June 2014.Medicine, Department ofMedicine, Faculty ofNeurology, Division ofReviewedFacult

Structural abnormalities in the cuneus associated with Herpes Simplex Virus (type 1) infection in people at ultra high risk of developing psychos

It has been suggested that some cases of schizophrenia may be caused by an interaction between physiological risk factors and exposure to certain neurotropic infectious agents such as Herpes Simplex Virus type 1 (HSV1). This study investigated whether HSV1 exposure was associated with structural brain abnormalities in individuals who, because of genetic or other factors, were deemed at ultra high risk (UHR) of developing psychosis. Twenty-five UHR individuals with a history of HSV1 exposure (HSV1. +), 33 UHR participants without a history of HSV1 exposure (HSV1. -) and 19 healthy controls participated in the study. All participants underwent a T1-weighted structural MRI scan, and HSV1 exposure was determined based on the presence of IgG class antibodies in the blood serum. Voxel based morphometry revealed that the HSV1. + participants exhibited volumetric gray matter reductions in the cuneus, relative to both the HSV1. - and healthy control participants (p