Table of Contents
List of Exhibits ix
Prologue: Why I Wrote This Book 1
Chapter 1 Precision Medicine 5
1.1 Definition 5
1.2 Proposal for the Precision Medicine Initiative 10
Chapter 2 Chidren's Hospital of Philadelphia (CHOP) 13
Chapter 3 Center for Applied Genomics (CAG) 17
Chapter 4 Attention Deficit Hyperactivity Disorder 22
Chapter 5 Autism Spectrum Disorder (ASD) 31
Chapter 6 22Q11.2 Deletion Syndrome (22Q) 38
6.1 Introduction to 22q 38
6.2 DiGeorge Syndrome 41
6.3 Velocardiofacial Syndrome (VCFS) 43
6.4 Conotruncal Anomaly Face Syndrome (CTAF) 44
6.5 Optiz G/BBB Syndrome 44
6.6 Cayler Cardiofacial Syndrome 44
6.7 Other Symptoms 45
6.8 Cognitive/Learning Problems 45
6.9 Endocrine System 46
6.10 Immunological Issues 47
6.11 Neurological/Brain Conditions 47
6.12 Problems in Infancy 47
6.13 Psychiatric/Psychological Issues 48
6.14 Skeletal/Muscle/Orthopedic/Spine Problems 48
6.15 Speech/Language Issues 48
6.16 Summary 49
6.17 Ten Questions about 22q That Further Research and Precision Medicine May Answer 49
6.18 Looking Forward 51
Chapter 7 Genetics 101 57
7.1 Genotype and Phenotype 59
7.2 Genes 61
7.3 DNA 62
7.4 Cells 66
7.5 Chromosomes 68
7.6 Mutations 69
7.7 Receptors 71
7.8 Gluten 73
7.9 Glutamate 74
7.10 Glutamate Receptors 75
7.11 Metabotropic Glutamate Receptors (mGluRs) 75
Chapter 8 Hakon Hakonarson 83
8.1 Medical School 83
8.2 Medical Residency and CHOP 84
8.3 Back to Iceland 85
8.4 Director of CAG 87
Chapter 9 Cag's Biobank 90
9.1 Obtaining Samples for the Biobank 91
9.2 Medical Records 93
9.3 Sequencing Laboratory 95
9.4 What makes CAG unique? 98
9.5 Use of a Large Biobank 99
9.6 Genotype/Phenotype Visualization 103
Chapter 10 The Discovery Process 110
10.1 Introduction 110
10.2 The Discovery Process 112
10.3 Target Identification 114
10.4 Single Nucleotide Polymorphisms (SNPs) and Copy Number Variations (CNVs) 116
10.5 Target Validation 119
10.6 Microarrays and Biomarkers 120
10.7 Remaining Tasks in the Drug Discovery Process 121
Chapter 11 The Discovery 126
11.1 The Target in the Discovery 126
11.2 Validation of the Target in the Discovery 131
11.3 Lead Identification-Finding a Drug 133
11.4 Summary of the Discovery 138
Chapter 12 Neurofix Therapeutics, INC 144
12.1 NeuroFix 144
12.2 Efforts to Obtain Financing 147
Chapter 13 Philip Harper 149
13.1 Background 149
13.2 Army Career 149
13.3 Business Career 150
13.4 United States Investigation Services, Inc. (USIS) 150
13.5 Hakon and Phil 152
13.6 Improving the neuroFix Business Plan 152
13.7 Financing Opportunities 154
13.8 Phil Invests in neuroFix 155
Chapter 14 Neurofix Option Agreement With Chop 156
14.1 The Option Agreement 156
14.2 Exercising the Option 159
14.3 CHOP Patents 159
Chapter 15 Clinical Trials 167
Chapter 16 Neurofix Contract with Nippon 174
16.1 Nippon Shinyaku Co. Ltd. (Nippon) 174
16.2 Nippon Agreement 175
Chapter 17 The Neurofix Clinical Trial 180
17.1 Background for neuroFix's Proposed Clinical Trial 180
17.2 Existing Treatment for ADHD Patients 185
17.3 Animal Studies 186
17.4 Selection of Patients for the Clinical Trial 190
17.5 Patient Regimen 193
17.6 Patient Reaction to the Drug 195
17.7 Results of the Clinical Trail 196
17.8 Explaining the Results of the Clinical Trial 201
Chapter 18 Neighborhood Drug Company 204
Chapter 19 Tripartite Deal 211
19.1 Negotiations with CHOP 211
19.2 Introduction of Medgenics 213
19.3 Tripartite Deal 216
19.4 NeuroFix and Medgenics Agreement with CHOP 216
19.5 NeuroFix and CHOP Agreement with Medgenics 219
19.6 Medgenics and CHOP Arrangement with Hakon Hakonarson 221
Chapter 20 Medgenics Clinical Trials 228
20.1 ADHD Non-interventional Clinical Trial 228
20.2 ADHD Interventional Clinical Trial 231
20.3 22q Clinical Trial 233
20.4 Expectations 237
20.5 Commercialization of NFC-I 239
20.6 Future Discoveries 240
20.7 Future Studies of Autism 241
Chapter 21 Criticism of Precision Medicine 253
21.1 The Problem with Precision Medicine 253
21.2 The Paradox of Precision Medicine 255
21.3 Precision Medicine: Hope, hype, or both 256
21.4 Response to the Critics of Precision Medicine 258
21.5 My personal experience with precision medicine 266
Chapter 22 Conclusion 281
Epilogue 285
Research Notes 287
A Hakon Hakonarson articles about ADHD (2009 - 201 6) 287
B Hakon Hakonarson articles about ASD (2009 - 201 6) 291
C List of references cited frequently 296
Acknowledgements 299
