Toward precision medicine in Parkinson's disease.

Precision medicine refers to an innovative approach selected for disease prevention and health promotion according to the individual characteristics of each patient. The goal of precision medicine is to formulate prevention and treatment strategies based on each individual with novel physiological and pathological insights into a certain disease. A multidimensional data-driven approach is about to upgrade "precision medicine" to a higher level of greater individualization in healthcare, a shift towards the treatment of individual patients rather than treating a certain disease including Parkinson's disease (PD). As one of the most common neurodegenerative diseases, PD is a lifelong chronic disease with clinical and pathophysiologic complexity, currently it is treatable but neither preventable nor curable. At its advanced stage, PD is associated with devastating chronic complications including both motor dysfunction and non-motor symptoms which impose an immense burden on the life quality of patients. Advances in computational approaches provide opportunity to establish the patient's personalized disease data at the multidimensional levels, which finally meeting the need for the current concept of precision medicine via achieving the minimal side effects and maximal benefits individually. Hence, in this review, we focus on highlighting the perspectives of precision medicine in PD based on multi-dimensional information about OMICS, molecular imaging, deep brain stimulation (DBS) and wearable sensors. Precision medicine in PD is expected to integrate the best evidence-based knowledge to individualize optimal management in future health care for those with PD.

[1]  E. Mayer,et al.  Gut/brain axis and the microbiota. , 2015, The Journal of clinical investigation.

[2]  Christian Duval,et al.  Are quantitative and clinical measures of bradykinesia related in advanced Parkinson's disease? , 2013, Journal of Neuroscience Methods.

[3]  Eric S. Lander,et al.  Cutting the Gordian helix--regulating genomic testing in the era of precision medicine. , 2015, The New England journal of medicine.

[4]  F Lhermitte,et al.  Does long‐term aggravation of Parkinson's disease result from nondopaminergic lesions? , 1987, Neurology.

[5]  I. McKeith,et al.  Motor subtype and cognitive decline in Parkinson’s disease, Parkinson’s disease with dementia, and dementia with Lewy bodies , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[6]  M. Neunlist,et al.  Activity‐dependent secretion of alpha‐synuclein by enteric neurons , 2013, Journal of neurochemistry.

[7]  D. Klonoff Precision Medicine for Managing Diabetes , 2015, Journal of diabetes science and technology.

[8]  G. Deuschl,et al.  MDS clinical diagnostic criteria for Parkinson's disease , 2015, Movement disorders : official journal of the Movement Disorder Society.

[9]  John F. Cryan,et al.  Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve , 2011, Proceedings of the National Academy of Sciences.

[10]  Jeffrey M. Hausdorff,et al.  Wearable Assistant for Parkinson’s Disease Patients With the Freezing of Gait Symptom , 2010, IEEE Transactions on Information Technology in Biomedicine.

[11]  Jeffrey M. Hausdorff,et al.  Identifying axial and cognitive correlates in patients with Parkinson’s disease motor subtype using the instrumented Timed Up and Go , 2013, Experimental Brain Research.

[12]  Grant D. Huang,et al.  Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease. , 2010, The New England journal of medicine.

[13]  L. Lannfelt,et al.  Immunotherapy targeting α-synuclein, with relevance for future treatment of Parkinson's disease and other Lewy body disorders. , 2014, Immunotherapy.

[14]  F. Horak,et al.  iTUG, a Sensitive and Reliable Measure of Mobility , 2010, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[15]  R. Dobbs,et al.  Peripheral aetiopathogenic drivers and mediators of Parkinson’s disease and co-morbidities: role of gastrointestinal microbiota , 2015, Journal of NeuroVirology.

[16]  B. Najafi,et al.  Precision Medicine: A Wider Definition , 2015, Journal of the American Geriatrics Society.

[17]  P. Damier,et al.  Colonic Biopsies to Assess the Neuropathology of Parkinson's Disease and Its Relationship with Symptoms , 2010, PloS one.

[18]  H. Forssberg,et al.  Normal gut microbiota modulates brain development and behavior , 2011, Proceedings of the National Academy of Sciences.

[19]  K. McCoy,et al.  The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. , 2011, Gastroenterology.

[20]  G. Petsko,et al.  Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations , 2015, The Lancet Neurology.

[21]  Michael J. Frank,et al.  Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism , 2007, Science.

[22]  Ned Jenkinson,et al.  Pedunculopontine Nucleus Stimulation Improves Gait Freezing in Parkinson Disease , 2011, Neurosurgery.

[23]  E. Pekkonen,et al.  Gut microbiota are related to Parkinson's disease and clinical phenotype , 2015, Movement disorders : official journal of the Movement Disorder Society.

[24]  P. Forsythe,et al.  Voices from within: gut microbes and the CNS , 2012, Cellular and Molecular Life Sciences.

[25]  H. Braak,et al.  Parkinson's disease: a dual‐hit hypothesis , 2007, Neuropathology and applied neurobiology.

[26]  R. Mach,et al.  Binding of the Radioligand SIL23 to α-Synuclein Fibrils in Parkinson Disease Brain Tissue Establishes Feasibility and Screening Approaches for Developing a Parkinson Disease Imaging Agent , 2013, PloS one.

[27]  Refet Firat Yazicioglu,et al.  Closing the loop for deep brain stimulation implants enables personalized healthcare for Parkinson's disease patients , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[28]  S. Haber,et al.  Closed-Loop Deep Brain Stimulation Is Superior in Ameliorating Parkinsonism , 2011, Neuron.

[29]  A. Probst,et al.  α‐Synuclein pathology of the spinal and peripheral autonomic nervous system in neurologically unimpaired elderly subjects , 2006, Neuropathology and applied neurobiology.

[30]  H. Braak,et al.  Gastric α-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology , 2006, Neuroscience Letters.

[31]  P. Bonato,et al.  Using Wearable Sensors to Enhance DBS Parameter Adjustment for Parkinson's Disease Patients Through Measures of Motor Response , 2006, 2006 3rd IEEE/EMBS International Summer School on Medical Devices and Biosensors.

[32]  Thomas O. Mera,et al.  Quantitative assessment of levodopa-induced dyskinesia using automated motion sensing technology , 2012, 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[33]  Hayriye Cagnan,et al.  Bilateral adaptive deep brain stimulation is effective in Parkinson's disease , 2015, Journal of Neurology, Neurosurgery & Psychiatry.

[34]  Thomas O. Mera,et al.  Feasibility of home-based automated Parkinson's disease motor assessment , 2012, Journal of Neuroscience Methods.

[35]  A. Brice,et al.  What genetics tells us about the causes and mechanisms of Parkinson's disease. , 2011, Physiological reviews.

[36]  Lorenzo Chiari,et al.  ISway: a sensitive, valid and reliable measure of postural control , 2012, Journal of NeuroEngineering and Rehabilitation.

[37]  María Teresa Arredondo,et al.  Gait assessment in Parkinson's disease patients through a network of wearable accelerometers in unsupervised environments , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[38]  K. Shannon,et al.  Is alpha‐synuclein in the colon a biomarker for premotor Parkinson's Disease? Evidence from 3 cases , 2012, Movement disorders : official journal of the Movement Disorder Society.

[39]  P. Brown,et al.  Adaptive Deep Brain Stimulation In Advanced Parkinson Disease , 2013, Annals of neurology.

[40]  Clement Hamani,et al.  Unilateral pedunculopontine stimulation improves falls in Parkinson's disease. , 2010, Brain : a journal of neurology.

[41]  Erika Check Hayden,et al.  Technology: The $1,000 genome , 2014, Nature.

[42]  J. Giuffrida,et al.  Objective motion sensor assessment highly correlated with scores of global levodopa-induced dyskinesia in Parkinson's disease. , 2013, Journal of Parkinson's disease.

[43]  Ron Alterman,et al.  Subthalamic deep brain stimulation with a constant-current device in Parkinson's disease: an open-label randomised controlled trial , 2012, The Lancet Neurology.

[44]  Joseph M Mahoney,et al.  Both coordination and symmetry of arm swing are reduced in Parkinson's disease. , 2012, Gait & posture.

[45]  Marcelo A. Wood,et al.  Automated scoring of fear-related behavior using EthoVision software , 2009, Journal of Neuroscience Methods.

[46]  Y. Agid,et al.  Clinical predictive factors of subthalamic stimulation in Parkinson's disease. , 2002, Brain : a journal of neurology.

[47]  Vincenzo Bonifati,et al.  The genetics of Parkinson's disease: Progress and therapeutic implications , 2013, Movement disorders : official journal of the Movement Disorder Society.

[48]  C. Duyckaerts,et al.  The second brain and Parkinson’s disease , 2009, The European journal of neuroscience.

[49]  Jeffrey M. Hausdorff,et al.  Objective Assessment of Fall Risk in Parkinson's Disease Using a Body-Fixed Sensor Worn for 3 Days , 2014, PloS one.

[50]  S E Ide,et al.  Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. , 1997, Science.

[51]  M. Helwig,et al.  Caudo-rostral brain spreading of α-synuclein through vagal connections , 2013, EMBO molecular medicine.

[52]  C. Ballard,et al.  Neuroimaging for Lewy body disease: Is the in vivo molecular imaging of α-synuclein neuropathology required and feasible? , 2010, Brain Research Reviews.

[53]  A. Benabid,et al.  Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. , 1987, Applied neurophysiology.

[54]  E. Benarroch,et al.  Neural control of the gastrointestinal tract: Implications for Parkinson disease , 2008, Movement disorders : official journal of the Movement Disorder Society.

[55]  B. Naliboff,et al.  Consumption of fermented milk product with probiotic modulates brain activity. , 2013, Gastroenterology.

[56]  J. Cummings,et al.  The role of dopaminergic imaging in patients with symptoms of dopaminergic system neurodegeneration. , 2011, Brain : a journal of neurology.

[57]  Hiroshi Mitoma,et al.  24-hour recording of parkinsonian gait using a portable gait rhythmogram. , 2010, Internal medicine.

[58]  T. Dinan,et al.  The impact of microbiota on brain and behavior: mechanisms & therapeutic potential. , 2014, Advances in experimental medicine and biology.

[59]  J. Obeso,et al.  Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up. , 2005, Brain : a journal of neurology.

[60]  Hayat Belaid,et al.  PPNa-DBS for gait and balance disorders in Parkinson’s disease: a double-blind, randomised study , 2015, Journal of Neurology.

[61]  Ali Keshavarzian,et al.  Colonic bacterial composition in Parkinson's disease , 2015, Movement disorders : official journal of the Movement Disorder Society.

[62]  Patrick T. Hickey,et al.  Neuroimaging of Parkinson's disease: Expanding views , 2015, Neuroscience & Biobehavioral Reviews.

[63]  A. Lang,et al.  Parkinson's disease subtypes: lost in translation? , 2012, Journal of Neurology, Neurosurgery & Psychiatry.

[64]  D. Devos,et al.  Colonic inflammation in Parkinson's disease , 2013, Neurobiology of Disease.

[65]  R. Mach,et al.  Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein , 2014, Applied sciences.

[66]  Elena Moro,et al.  New targets for deep brain stimulation treatment of Parkinson’s disease , 2013, Expert review of neurotherapeutics.

[67]  Jeffrey H. Kordower,et al.  Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson's Disease , 2011, PloS one.

[68]  E. Mayer,et al.  Principles and clinical implications of the brain–gut–enteric microbiota axis , 2009, Nature Reviews Gastroenterology &Hepatology.

[69]  N. Quinn,et al.  “Atypical” atypical parkinsonism: New genetic conditions presenting with features of progressive supranuclear palsy, corticobasal degeneration, or multiple system atrophy—A diagnostic guide , 2013, Movement disorders : official journal of the Movement Disorder Society.

[70]  Luca Palmerini,et al.  Balance Testing With Inertial Sensors in Patients With Parkinson's Disease: Assessment of Motor Subtypes , 2014, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[71]  Dimitrios I. Fotiadis,et al.  An automated methodology for levodopa-induced dyskinesia: Assessment based on gyroscope and accelerometer signals , 2012, Artif. Intell. Medicine.

[72]  F. Collins,et al.  A new initiative on precision medicine. , 2015, The New England journal of medicine.

[73]  D J Brooks,et al.  Advances in imaging Parkinson's disease. , 1997, Current opinion in neurology.

[74]  T. Dinan,et al.  Mind-altering Microorganisms: the Impact of the Gut Microbiota on Brain and Behaviour , 2022 .

[75]  Peter Brown,et al.  Deep brain stimulation of the subthalamic nucleus: A two-edged sword , 2006, Current Biology.

[76]  H. Braak,et al.  Staging of brain pathology related to sporadic Parkinson’s disease , 2003, Neurobiology of Aging.

[77]  J. Bienenstock,et al.  Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents. , 2013, American journal of physiology. Gastrointestinal and liver physiology.

[78]  D. Longo,et al.  Precision medicine--personalized, problematic, and promising. , 2015, The New England journal of medicine.

[79]  M. Blaser The microbiome revolution. , 2014, The Journal of clinical investigation.