Emerging therapies for Parkinson's disease: from bench to bedside.
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 A2A 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.
Department of Psychiatry and Neuroscience Program, Harvard Medical School, McLean Hospital, Belmont, MA 02478, USA. Electronic address: ftarazi@hms.harvard.edu.
F I
FI
Tarazi
Department of Psychiatry and Neuroscience Program, Harvard Medical School, McLean Hospital, Belmont, MA 02478, USA; School of Medicine, American University of Beirut, Beirut, Lebanon.
Z T
ZT
Sahli
The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.
M
M
Wolny
The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.
S A
SA
Mousa
D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000494:pharmacology; D046690:Deep Brain Stimulation / Q000379:methods; D015316:Genetic Therapy / Q000379:methods; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors; D053860:Pallidotomy / Q000379:methods; D010300:Parkinson Disease / Q000628:therapy*; D016634:Radiosurgery; D033581:Stem Cell Transplantation; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D011503:Transglutaminases / Q000037:antagonists & inhibitors
D058917:Adenosine A2 Receptor Antagonists; D051017:Apoptosis Regulatory Proteins; C469991:DDIT4 protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D014157:Transcription Factors; D011503:Transglutaminases; D020930:MAP Kinase Kinase Kinases
Adenosine A(2A) antagonists; Anti-apoptotic agents; Deep brain stimulation; Pallidotomy; Stem cells; Viral vector gene therapy