Emerging therapies for Parkinson's disease: From bench to bedside

被引:73
作者
Tarazi, F. I. [1 ,2 ]
Sahli, Z. T. [1 ,2 ,4 ]
Wolny, M. [3 ]
Mousa, S. A. [3 ]
机构
[1] Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA
[2] Harvard Univ, Sch Med, McLean Hosp, Neurosci Program, Belmont, MA 02478 USA
[3] Albany Coll Pharm & Hlth Sci, Pharmaceut Res Inst, Rensselaer, NY 12144 USA
[4] Amer Univ Beirut, Sch Med, Beirut, Lebanon
关键词
Adenosine A(2A) antagonists; Anti-apoptotic agents; Deep brain stimulation; Pallidotomy; Stem cells; Viral vector gene therapy; DEEP-BRAIN-STIMULATION; LEVODOPA-INDUCED DYSKINESIAS; GAMMA-KNIFE THALAMOTOMY; HIGH-FREQUENCY STIMULATION; NEUROTROPHIC FACTOR; GENE-THERAPY; DOPAMINERGIC-NEURONS; GLUTAMATE RECEPTORS; MITOCHONDRIAL DYSFUNCTION; OXIDATIVE STRESS;
D O I
10.1016/j.pharmthera.2014.05.010
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The prevalence of Parkinson's disease (PD) increases with age and is projected to increase in parallel to the rising average age of the population. The disease can have significant health-related, social, and financial implications not only for the patient and the caregiver, but for the health care system as well. While the neuropathology of this neurodegenerative disorder is fairly well understood, its etiology remains a mystery, making it difficult to target therapy. The currently available drugs for treatment provide only symptomatic relief and do not control or prevent disease progression, and as a result patient compliance and satisfaction are low. Several emerging pharmacotherapies for PD are in different stages of clinical development. These therapies include adenosine A(2A) receptor antagonists, glutamate receptor antagonists, monoamine oxidase inhibitors, anti-apoptotic agents, and antioxidants such as coenzyme Q10, N-acetyl cysteine, and edaravone. Other emerging non-pharmacotherapies include viral vector gene therapy, microRNAs, transglutaminases, RTP801, stem cells and glial derived neurotrophic factor (GDNF). In addition, surgical procedures including deep brain stimulation, pallidotomy, thalamotomy and gamma knife surgery have emerged as alternative interventions for advanced PD patients who have completely utilized standard treatments and still suffer from persistent motor fluctuations. While several of these therapies hold much promise in delaying the onset of the disease and slowing its progression, more pharmacotherapies and surgical interventions need to be investigated in different stages of PD. It is hoped that these emerging therapies and surgical procedures will strengthen our clinical armamentarium for improved treatment of PD.
引用
收藏
页码:123 / 133
页数:11
相关论文
共 217 条
[1]  
Abbruzzese G, 2012, FUNCT NEUROL, V27, P147
[2]   THE FUNCTIONAL-ANATOMY OF BASAL GANGLIA DISORDERS [J].
ALBIN, RL ;
YOUNG, AB ;
PENNEY, JB .
TRENDS IN NEUROSCIENCES, 1989, 12 (10) :366-375
[3]   Tissue trans glutaminase catalyzes the formation of alpha-synuclein crosslinks in Parkinson's disease [J].
Andringa, G ;
Lam, KY ;
Chegary, M ;
Wang, X ;
Chase, TN ;
Bennett, MC .
FASEB JOURNAL, 2004, 18 (03) :932-+
[4]  
[Anonymous], GLOB PUBLIC HEALTH
[5]   Duodenal levodopa infusion for advanced Parkinson's disease: 12-month treatment outcome [J].
Antonini, Angelo ;
Isaias, Ioannis U. ;
Canesi, Margherita ;
Zibetti, Maurizio ;
Mancini, Francesca ;
Manfredi, Luigi ;
Dal Fante, Marco ;
Lopiano, Leonardo ;
Pezzoli, Gianni .
MOVEMENT DISORDERS, 2007, 22 (08) :1145-1149
[6]   Pros and cons of apomorphine and L-dopa continuous infusion in advanced Parkinson's disease [J].
Antonini, Angelo ;
Odin, Per .
PARKINSONISM & RELATED DISORDERS, 2009, 15 :S97-S100
[7]   N-acetyl-cysteine in the treatment of Parkinson's disease. What are we waiting for? [J].
Arturo Martinez-Banaclocha, Marcos .
MEDICAL HYPOTHESES, 2012, 79 (01) :8-12
[8]   Clinical utility of dopamine transporter single photon emission CT (DaT-SPECT) with (123I) ioflupane in diagnosis of parkinsonian syndromes [J].
Bajaj, Nin ;
Hauser, Robert A. ;
Grachev, Igor D. .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2013, 84 (11) :1288-1295
[9]   Brain dopamine receptors: A primer on their current status, basic and clinical [J].
Baldessarini, RJ ;
Tarazi, FI .
HARVARD REVIEW OF PSYCHIATRY, 1996, 3 (06) :301-325
[10]   N-Acetylcysteine elicited increase in complex I activity in synaptic mitochondria from aged mice:: implications for treatment of Parkinson's disease [J].
Banaclocha, MM .
BRAIN RESEARCH, 2000, 859 (01) :173-175