A

References

Abbott, A. 2011. Novartis to shut brain research facility. Nature 480(7376):161-162.

Altar, C. A., M. P. Vawter, and S. D. Ginsberg. 2009. Target identification for CNS diseases by transcriptional profiling. Neuropsychopharmacol 34(1):18-54.

Apud, J. A., F. Zhang, H. Decot, K. L. Bigos, and D. R. Weinberger. 2012. Genetic variation in KCNH2 associated with expression in the brain of a unique hERG isoform modulates treatment response in patients with schizophrenia. Am J Psychiat 169(7):725-734.

Banasr, M., J. M. Dwyer, and R. S. Duman. 2011. Cell atrophy and loss in depression: Reversal by antidepressant treatment. Curr Opin Cell Biol 23(6):730-737.

Bear, M. F., K. M. Huber, and S. T. Warren. 2004. The mGluR theory of fragile X mental retardation. Trends Neurosci 27(7):370-377.

Bhakar, A. L., G. Dölen, and M. F. Bear. 2012. The pathophysiology of fragile X (and what it teaches us about synapses). Annu Rev Neurosci 35:417-443.

Bolker, J. 2012. Model organisms: There’s more to life than rats and flies. Nat 491(7422):31-33.

Brandon, M. J., M. Malamas, N. Hoefgen, and T. Hage. 2008. PDE10 inhibition for the treatment of schizophrenia. Schizophr Res 102(1, Suppl. 2):39.

Bunnage, M. E. 2011. Getting pharmaceutical R&D back on target. Nat Chem Biol 7(6):335-339.

Cambridge Healthtech Institute. 2013. Drug targets and disease targets glossary and taxonomy. http://www.genomicglossaries.com/content/Targets.asp (accessed October 23, 2013).

Couzin, J. 2007. ALS trial raises questions about promising drug. Science 318(5854):1227.



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A References Abbott, A. 2011. Novartis to shut brain research facility. Nature 480(7376):161- 162. Altar, C. A., M. P. Vawter, and S. D. Ginsberg. 2009. Target identification for CNS diseases by transcriptional profiling. Neuropsychopharmacol 34(1):18-54. Apud, J. A., F. Zhang, H. Decot, K. L. Bigos, and D. R. Weinberger. 2012. Ge- netic variation in KCNH2 associated with expression in the brain of a unique hERG isoform modulates treatment response in patients with schiz- ophrenia. Am J Psychiat 169(7):725-734. Banasr, M., J. M. Dwyer, and R. S. Duman. 2011. Cell atrophy and loss in de- pression: Reversal by antidepressant treatment. Curr Opin Cell Biol 23(6):730-737. Bear, M. F., K. M. Huber, and S. T. Warren. 2004. The mGluR theory of fragile X mental retardation. Trends Neurosci 27(7):370-377. Bhakar, A. L., G. Dölen, and M. F. Bear. 2012. The pathophysiology of fragile X (and what it teaches us about synapses). Annu Rev Neurosci 35:417-443. Bolker, J. 2012. Model organisms: There’s more to life than rats and flies. Nat 491(7422):31-33. Brandon, M. J., M. Malamas, N. Hoefgen, and T. Hage. 2008. PDE10 inhibition for the treatment of schizophrenia. Schizophr Res 102(1, Suppl. 2):39. Bunnage, M. E. 2011. Getting pharmaceutical R&D back on target. Nat Chem Biol 7(6):335-339. Cambridge Healthtech Institute. 2013. Drug targets and disease targets glossary and taxonomy. http://www.genomicglossaries.com/content/Targets.asp (accessed October 23, 2013). Couzin, J. 2007. ALS trial raises questions about promising drug. Science 318(5854):1227. 79

OCR for page 79
80 THERAPEUTIC DEVELOPMENT FOR NERVOUS SYSTEM DISORDERS Dimos, J. T., K. T. Rodolfa, K. K. Niakan, L. M. Weisenthal, H. Mitsumoto, W. Chung, G. F. Croft, G. Saphier, R. Leibel, R. Goland, H. Wichterle, C. E. Henderson, and K. Eggan. 2008. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321(5893):1218-1221. Dölen, G., E. Osterweil, B. S. Rao, G. B. Smith, B. D. Auerbach, S. Chattarji, and M. F. Bear. 2007. Correction of fragile X syndrome in mice. Neuron 56(6):955-962. Drevets, W. C., J. L. Price, J. R. Simpson, Jr., R. D. Todd, T. Reich, M. Vannier, and M. E. Raichle. 1997. Subgenual prefrontal cortex abnormalities in mo- od disorders. Nature 386(6627):824-827. Drevets, W. C., J. Savitz, and M. Trimble. 2008. The subgenual anterior cingu- late cortex in mood disorders. CNS Spectr 13(8):663-681. Duff, K., and F. Suleman. 2004. Transgenic mouse models of Alzheimer’s dis- ease: How useful have they been for therapeutic development? Brief Funct Genomic Proteomic 3(1):47-59. Duman, R. S., and G. K. Aghajanian. 2012. Synaptic dysfunction in depression: Potential therapeutic targets. Science 338(6103):68-72. Duman, R. S., N. Li, R. J. Liu, V. Duric, and G. Aghajanian. 2012. Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacol 62(1):35-41. Egan, M. F., R. E. Straub, T. E. Goldberg, I. Yakub, J. H. Callicott, A. R. Hariri, V. S. Mattay, A. Bertolino, T. M. Hyde, C. Shannon-Weickert, M. Akil, J. Crook, R. K. Vakkalanka, R. Balkissoon, R. A. Gibbs, J. E. Kleinman, and D. R. Weinberger. 2004. Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. P Natl Acad Sci USA 101(34):12604- 12609. Epi4K Consortium. 2012. Epi4K: Gene discovery in 4,000 genomes. Epilepsia 53(8):1457-1467. European Commission. 2010. Sixth report on the statistics on the number of animals used for experimental and other scientific purposes in the Member States of the European Union. Brussels, Belgium: European Commission. http://ec.europa.eu/environment/chemicals/lab_animals/reports_en.htm (ac- cessed July 2, 2013). FDA (U.S. Food and Drug Administration). 2005a. Guidance for industry: Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. http://www.fda. gov/downloads/Drugs/Guidances/UCM078932.pdf (accessed April 10, 2013). FDA. 2005b. Guidance for industry, investigators, and reviewers: Exploratory IND studies. http://www.fda.gov/downloads/drugs/GuidanceCompliance RegulatoryInformation/Guidances/UCM0708933.pdf (accessed April 10, 2013).

OCR for page 79
APPENDIX A 81 FDA. 2013a. Fact sheet: Breakthrough therapies. http://www.fda.gov/Regulatory information/Legislation/FederalFoodDrugandCosmeticActFDCAct/Significant AmendmentstotheFDCAct/FDASIA/ucm329491.htm (accessed May 23, 2013). FDA. 2013b. Fast track, accelerated approval and priority review. http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/speeding accesstoimportantnewtherapies/ucm128291.htm (accessed May 23, 2013). Fishman, M. C. 2013. Power of rare diseases: Found in translation. Sci Transl Med 5(201):201ps11. Fleming, T. R., and J. H. Powers. 2012. Biomarkers and surrogate endpoints in clinical trials. Stat Med 31(25):2973-2984. Freund, P., T. Wannier, E. Schmidlin, J. Bloch, A. Mir, M. E. Schwab, and E. M. Rouiller. 2007. Anti-Nogo-A antibody treatment enhances sprouting of corticospinal axons rostral to a unilateral cervical spinal cord lesion in adult macaque monkey. J Comp Neurol 502(4):644-659. Gashaw, I., P. Ellinghaus, A. Sommer, and K. Asadullah. 2011. What makes a good drug target? Drug Discov Today 16(23-24):1037-1043. Giampà, C., D. Laurenti, S. Anzilotti, G. Bernardi, F. S. Menniti, and F. R. Fusco. 2010. Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Hunting- ton’s disease. PLoS ONE 5(10):e13417. Grskovic, M., A. Javaherian, B. Strulovici, and G. Q. Daley. 2011. Induced plu- ripotent stem cells—opportunities for disease modeling and drug discovery. Nat Rev Drug Discov 10(12):915-929. Hristov, M., W. Erl, and P. C. Weber. 2003. Endothelial progenitor cells: Mobi- lization, differentiation, and homing. Arterioscl Throm Vas 23(7):1185- 1189. Huffaker, S. J., J. Chen, K. K. Nicodemus, F. Sambataro, F. Yang, V. Mattay, B. K. Lipska, T. M. Hyde, J. Song, D. Rujescu, I. Giegling, K. Mayilyan, M. J. Proust, A. Soghoyan, G. Caforio, J. H. Callicott, A. Bertolino, A. Meyer-Lindenberg, J. Chang, Y. Ji, M. F. Egan, T. E. Goldberg, J. E. Kleinman, B. Lu, and D. R. Weinberger. 2009. A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolar- ization and risk of schizophrenia. Nat Med 15(5):509-518. Hyman, S. E. 2012. Revolution stalled. Sci Transl Med 4(155):155cm11. Insel, T. R. 2012a. Next-generation treatments for mental disorders. Sci Transl Med 4(155):155ps19. Insel, T. R. 2012b. Experimental medicine. National Institute of Mental Health director’s blog July 12. http://www.nimh.nih.gov/about/director/2012/ experimental-medicine.shtml (accessed May 7, 2013). IOM (Institute of Medicine). 2011. Glutamate-related biomarkers in drug de- velopment for disorders of the nervous system: Workshop summary. Wash- ington, DC: The National Academies Press. P. 34.

OCR for page 79
82 THERAPEUTIC DEVELOPMENT FOR NERVOUS SYSTEM DISORDERS IOM. 2013. Improving the utility and translation of animal models for nervous system disorders: Workshop summary. Washington, DC: The National Academies Press. Israel, M. A., S. H. Yuan, C. Bardy, S. M. Reyna, Y. Mu, C. Herrera, M. P. Hefferan, S. Van Gorp, K. L. Nazor, F. S. Boscolo, C. T. Carson, L. C. Laurent, M. Marsala, F. H. Gage, A. M. Remes, E. H. Koo, and L. S. Goldstein. 2012. Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature 482(7384):216-220. Kim, S. H., P. E. Fraser, D. Westaway, P. H. St George-Hyslop, M. E. Ehrlich, and S. Gandy. 2010. Group II metabotropic glutamate receptor stimulation triggers production and release of Alzheimer’s amyloid(beta)42 from isolat- ed intact nerve terminals. J Neurosci 30(11):3870-3875. Kishida, K. T., B. King-Casas, and P. R. Montague. 2010. Neuroeconomic ap- proaches to mental disorders. Neuron 67(4):543-554. Konopka, G., J. M. Bomar, K. Winden, G. Coppola, Z. O. Jonsson, F. Gao, S. Peng, T. M. Preuss, J. A. Wohlschlegel, and D. H. Geschwind. 2009. Human-specific transcriptional regulation of CNS development genes by FOXP2. Nature 462(7270):213-217. Konopka, G., T. Friedrich, J. Davis-Turak, K. Winden, M. C. Oldham, F. Gao, L. Chen, G. Z. Wang, R. Luo, T. M. Preuss, and D. H. Geschwind. 2012. Human-specific transcriptional networks in the brain. Neuron 75(4):601- 617. Krystal, J. H., E. B. Perry, Jr., R. Gueorguieva, A. Belger, S. H. Madonick, A. Abi-Dargham, T. B. Cooper, L. Macdougall, W. Abi-Saab, and D. C. D’Souza. 2005. Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine: Implications for glutamatergic and dopaminergic model psychoses and cognitive function. Arch Gen Psychiat 62(9):985-994. Leaf, C. 2013 (July 13). Do clinical trials work? New York Times. http:///www. nytimes.com/2013/07/14/opinion/sunday/do-clinical-trials-work.html?_r=0 (accessed October 22, 2013). Lee, J. H., S. Barral, and C. Reitz. 2008. The neuronal sortilin-related receptor gene SORL1 and late-onset Alzheimer’s disease. Curr Neurol Neurosci 8(5):384-391. Manji, H. K., C. W. Drevets, and D. S. Charney. 2001. The cellular neurobiolo- gy of depression. Nat Med 7(5):541-547. Marklund, N., F. M. Bareyre, N. C. Royo, H. J. Thompson, A. K. Mir, M. S. Grady, M. E. Schwab, and T. K. McIntosh. 2007. Cognitive outcome fol- lowing brain injury and treatment with an inhibitor of Nogo-A in associa- tion with an attenuated downregulation of hippocampal growth-associated protein-43 expression. J Neurosurg 107(4):844-853. Mayberg, H. S., A. M. Lozano, V. Voon, H. E. McNeely, D. Seminowicz, C. Hamani, J. M. Schwalb, and S. H. Kennedy. 2005. Deep brain stimulation for treatment-resistant depression. Neuron 45(5):651-660.

OCR for page 79
APPENDIX A 83 McCune, J. M., R. Namikawa, H. Kaneshima, L. D. Shultz, M. Lieberman, and I. L. Weissman. 1988. The SCID-hu mouse: Murine model for the analysis of human hematolymphoid differentiation and function. Science 241 (4873):1632-1639. Miller, G. 2010. Is Pharma running out of brainy ideas? Science 329(5991):502- 504. Montague, P. R., P. Dayan, and T. J. Sejnowski. 1996. A framework for mesencephalic dopamine systems based on predictive Hebbian learning. J Neurosci 16(5):1936-1947. Moore, G. J., B. M. Cortese, D. A. Glitz, C. Zajac-Benitez, J. A. Quiroz, T. W. Uhde, W. C. Drevets, and H. K. Manji. 2009. A longitudinal study of the ef- fects of lithium treatment on prefrontal and subgenual prefrontal gray mat- ter volume in treatment-responsive bipolar disorder patients. J Clin Psychiat 70(5):699-705. Moreno, H., W. E. Wu, T. Lee, A. Brickman, R. Mayeux, T. R. Brown, and S. A. Small. 2007. Imaging the Abeta-related neurotoxicity of Alzheimer disease. Arch Neurol 64(10):1467-1477. NIH (National Institutes of Health). 2002. Stem cell basics: Introduction. http://stemcells.nih.gov/info/basics/pages/basics1.aspx (accessed September 30, 2013). NINDS (National Institute of Neurological Disorders and Stroke). 2010. NINDS encephalopathy information page. http://www.ninds,nih,gov/disorders/ encephalopathy/encephalopathy.htm (accessed August 28, 2013). Norman, T., A. Edwards, C. Bountra, and S. Friend. 2011. The precompetitive space: Time to move the yardsticks. Sci Transl Med 3(76):76cm10. Orth, A. P., S. Batalov, M. Perrone, and S. K. Chanda. 2004. The promise of genomics to identify novel therapeutic targets. Expert Opin Ther Tar 8(6):587-596. Ostrowitzki, S., D. Deptula, L. Thurfjell, F. Barkhof, B. Bohrmann, D. J. Brooks, W. E. Klunk, E. Ashford, K. Yoo, Z. X. Xu, H. Loetscher, and L. Santarelli. 2012. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol 69(2):198-207. Paul, S. M., D. S. Mytelka, C. T. Dunwiddie, C. C. Persinger, B. H. Munos, S. R. Lindborg, and A. L. Schacht. 2010. How to improve R&D productivi- ty: The pharmaceutical industry’s grand challenge. Nat Rev Drug Discov 9(3):203-214. Pereira, A. C., D. E. Huddleston, A. M. Brickman, A. A. Sosunov, R. Hen, G. M. McKhann, R. Sloan, F. H. Gage, T. R. Brown, and S. A. Small. 2007. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. P Natl Acad Sci USA 104(13):5638-5643. Perrin, R. J., A. M. Fagan, and D. M. Holtzman. 2009. Multimodal techniques for diagnosis and prognosis of Alzheimer’s disease. Nature 461(7266):916- 922.

OCR for page 79
84 THERAPEUTIC DEVELOPMENT FOR NERVOUS SYSTEM DISORDERS Pizzagalli, D. A. 2011. Frontocingulate dysfunction in depression: Toward bi- omarkers of treatment response. Neuropsychopharmacol 36(1):183-206. Reitz, C. 2012. Alzheimer’s disease and the amyloid cascade hypothesis: A crit- ical review. Int J Alzheimer’s Dis 2012(2012):369808. Rinne, J. O., D. J. Brooks, M. N. Rossor, N. C. Fox, R. Bullock, W. E. Klunk, C. A. Mathis, K. Blennow, J. Barakos, A. A. Okello, S. Rodriguez Martinez de Liano, E. Liu, M. Koller, K. M. Gregg, D. Schenk, R. Black, and M. Grundman. 2010. 11C-PiB PET assessment of change in fibrillar amyloid- beta load in patients with Alzheimer’s disease treated with bapineuzumab: A phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol 9(4):363-372. Riordan, H. J., and N. R. Cutler. 2010. The death of CNS drug development: Overstatement or omen? J Clinical Studies 3(6):12-15. Rizzo, S. J., J. R. Edgerton, Z. A. Hughes, and N. J. Brandon. 2013. Future via- ble models of psychiatry drug discovery in pharma. J Biomol Screen 18(5):509-521. Rowe, C. C., K. A. Ellis, M. Rimajova, P. Bourgeat, K. E. Pike, G. Jones, J. Fripp, H. Tochon-Danguy, L. Morandeau, G. O’Keefe, R. Price, P. Raniga, P. Robins, O. Acosta, N. Lenzo, C. Szoeke, O. Salvado, R. Head, R. Martins, C. L. Masters, D. Ames, and V. L. Villemagne. 2010. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging 31(8):1275-1283. Rubin, L. L. 2008. Stem cells and drug discovery: The beginning of a new era? Cell 132(4):549-552. Rudin, M., and R. Weissleder. 2003. Molecular imaging in drug discovery and development. Nat Rev Drug Discov 2(2):123-131. Salvadore, G., A. C. Nugent, H. Lemaitre, D. A. Luckenbaugh, R. Tinsley, D. M. Cannon, A. Neumeister, C. A. Zarate, Jr., and W. C. Drevets. 2011. Prefrontal cortical abnormalities in currently depressed versus currently re- mitted patients with major depressive disorder. Neuroimage 54(4):2643- 2651. Sartorius, L. J., G. Nagappan, B. K. Lipska, B. Lu, Y. Sei, R. Ren-Patterson, Z. Li, D. R. Weinberger, and P. J. Harrison. 2006. Alternative splicing of hu- man metabotropic glutamate receptor 3. J Neurochem 96(4):1139-1148. Sartorius, L. J., D. R. Weinberger, T. M. Hyde, P. J. Harrison, J. E. Kleinman, and B. K. Lipska. 2008. Expression of a GRM3 splice variant is increased in the dorsolateral prefrontal cortex of individuals carrying a schizophrenia risk SNP. Neuropsychopharmacol 33(11):2626-2634. Savitz, J. B., S. L. Rauch, and W. C. Drevets. 2013. Clinical application of brain imaging for the diagnosis of mood disorders: The current state of play. Mol Psychiatr 18(5):528-539.

OCR for page 79
APPENDIX A 85 Schobel, S. A., N. M. Lewandowski, C. M. Corcoran, H. Moore, T. Brown, D. Malaspina, and S. A. Small. 2009. Differential targeting of the CA1 sub- field of the hippocampal formation by schizophrenia and related psychotic disorders. Arch Gen Psychiat 66(9):938-946. Schobel, S. A., N. H. Chaudhury, U. A. Khan, B. Paniagua, M. A. Styner, I. Asllani, B. P. Inbar, C. M. Corcoran, J. A. Lieberman, H. Moore, and S. A. Small. 2013. Imaging patients with psychosis and a mouse model establish- es a spreading pattern of hippocampal dysfunction and implicates glutamate as a driver. Neuron 78(1):81-93. Schughart, K., C. Libert, and M. J. Kas. 2012. Human disease: Strength to strength for mouse models. Nat 492(7427):41. Segal, E., M. Shapira, A. Regev, D. Pe’er, D. Botstein, D. Koller, and N. Friedman. 2003. Module networks: Identifying regulatory modules and their condition-specific regulators from gene expression data. Nat Genet 34(2):166-176. Seok, J., H. S. Warren, A. G. Cuenca, M. N. Mindrinos, H. V. Baker, W. Xu, D. R. Richards, G. P. McDonald-Smith, H. Gao, L. Hennessy, C. C. Finnerty, C. M. López, S. Honari, E. E. Moore, J. P. Minei, J. Cuschieri, P. E. Bankey, J. L. Johnson, J. Sperry, A. B. Nathens, T. R. Billiar, M. A. West, M. G. Jeschke, M. B. Klein, R. L. Gamelli, N. S. Gibran, B. H. Brownstein, C. Miller-Graziano, S. E. Calvano, P. H. Mason, J. P. Cobb, L. G. Rahme, S. F. Lowry, R. V. Maier, L. L. Moldawer, D. N. Herndon, R. W. Davis, W. Xiao, R. G. Tompkins, and Inflammation and Host Re- sponse to Injury, Large Scale Collaborative Research Program. 2013. Ge- nomic responses in mouse models poorly mimic human inflammatory diseases. P Natl Acad Sci USA 110(9):3507-3512. Serretti, A., and C. Fabbri. 2013. Shared genetics among major psychiatric dis- orders. Lancet 381(9875):1339-1341. Small, S. A., W. Y. Tsai, R. DeLaPaz, R. Mayeux, and Y. Stern. 2002. Imaging hippocampal function across the human life span: Is memory decline nor- mal or not? Ann Neurol 51(3):290-295. Small, S. A., M. K. Chawla, M. Buonocore, P. R. Rapp, and C. A. Barnes. 2004. Imaging correlates of brain function in monkeys and rats isolates a hippo- campal subregion differentially vulnerable to aging. P Natl Acad Sci USA 101(18):7181-7186. Sperling, R. A., P. S. Laviolette, K. O’Keefe, J. O’Brien, D. M. Rentz, M. Pihlajamaki, G. Marshall, B. T. Hyman, D. J. Selkoe, T. Hedden, R. L. Buckner, J. A. Becker, and K. A. Johnson. 2009. Amyloid deposition is as- sociated with impaired default network function in older persons without dementia. Neuron 63(2):178-188. Tan, H. Y., J. H. Callicott, and D. R. Weinberger. 2007. Dysfunctional and com- pensatory prefrontal cortical systems, genes and the pathogenesis of schizo- phrenia. Cereb Cortex 17(Suppl. 1):i171-i181.

OCR for page 79
86 THERAPEUTIC DEVELOPMENT FOR NERVOUS SYSTEM DISORDERS Temple R. J. 1995. A regulatory authority’s opinion about surrogate endpoints. In Clinical Measurement in Drug Evaluation, edited by W. S. Nimmo and G. T. Tucker. New York: John Wiley. P. 790. Thurman, D. J., C. Alverson, K. A. Dunn, J. Guerrero, and J. E. Sniezek. 1999. Traumatic brain injury in the United States: A public health perspective. J Head Trauma Rehab 14(6):602-615. Tufts Center for the Study of Drug Development (CSDD). 2012. Drugs to treat CNS diseases take 35% longer to develop than other drugs. http://csdd.tufts.edu/news/complete_story/pr_ir_marapr_2012 (accessed August 28, 2013). Uchida, N., D. W. Buck, D. He, M. J. Reitsma, M. Masek, T. V. Phan, A. S. Tsukamoto, F. H. Gage, and I. L. Weissman. 2000. Direct isolation of hu- man central nervous system stem cells. P Natl Acad Sci USA 97(26):14720- 14725. Warner, M. A., T. S. Youn, T. Davis, A. Chandra, C. Marquez de la Plata, C. Moore, C. Harper, C. J. Madden, J. Spence, R. McColl, M. Devous, R. D. King, and R. Diaz-Arrastia. 2010. Regionally selective atrophy after trau- matic axonal injury. Arch Neurol 67(11):1336-1344. Wegener, G., and D. Rujescu. 2013. The current development of CNS drug re- search. Int J Neuropsychoph 16(7):1687-1693. Willmann, J. K., N. van Bruggen, L. M. Dinkelborg, and S. S. Gambhir. 2008. Molecular imaging in drug development. Nat Rev Drug Discov 7(7):591- 607. Yang, S., X. Wang, J. Liu, Z. Liu, and J. Huang. 2011. The applications of in- duced pluripotent stem (iPS) cells in drug development. Front Biol 6(1):52- 57. Young, J. E., and L. S. Goldstein. 2012. Alzheimer’s disease in a dish: Promises and challenges of human stem cell models. Hum Mol Genet 21(R1):R82- R89.