New and emerging medical therapies in Parkinson’s disease

ABSTRACT

Introduction: Parkinson’s disease (PD) is one of the most challenging neurodegenerative disorders to treat as it manifests with a large variety of troublesome, and often disabling, motor and non-motor symptoms. Despite limitations, such as motor and other complications, levodopa remains the most effective drug in the treatment of PD.

Areas covered: In this review, we focus on phase 2 and 3 studies describing new and emerging medical therapies in PD. We discuss new formulations of levodopa, medications that prolong levodopa response and ameliorate levodopa-induced dyskinesias, and innovative delivery methods that are currently being evaluated in clinical trials or are in development with the promise of better efficacy and tolerability. We also describe novel non-dopaminergic drugs that have been identified for treatment of motor and non-motor symptoms. A specific section is designated for potential disease modifying therapies.

Expert Opinion: Alternative formulations of levodopa appear to be promising especially to help with the motor fluctuations either by providing sustained benefits with controlled released formulations or ameliorate sudden OFF by formulations such as inhaled levodopa. Several different medications affecting non-dopaminergic pathways are being evaluated which may aide levodopa. As the understanding of the disease grows further, numerous novel neuroprotective or disease modifying therapies have been suggested. This along with development of medications to treat various non-motor symptoms will help improve quality of life of patients with PD.

KEYWORDS:

• Emerging therapies
• Parkinson
• disease modifying therapies
• levodopa
• neuroprotection
• levodopa induced dyskinesia
• neuroprotection
• nondopaminergic drug
• α-synuclein
• amantadine

Article highlights

• Levodopa remains the mainstay of anti-PD treatment.

• New formulations of levodopa are being investigated in attempt to improve its pharmacokinetics and prevent or treat levodopa-related motor complications.

• Medications affecting non-dopaminergic pathways have been recently approved and will soon be approved for the treatment of levodopa-related complications and non-motor symptoms of PD. There has been an explosion of studies attempting to slow the progression of this neurodegenerative disorder.

• Improved treatment options for management of non-motor symptoms.

This box summarizes key points contained in the article.

Declaration of interest

J Jankovic has received research grants from: Adamas Pharmaceuticals, Inc; Allergan, Inc; Auspex Pharmaceuticals, Inc; CHDI Foundation; Civitas/Acorda Therapeutics; Huntington Study Group; Ipsen Limited; Kyowa Haako Kirin Pharma, Inc; Lundbeck Inc; Medtronic; Merz Pharmaceuticals; Michael J Fox Foundation for Parkinson Research; National Institutes of Health; National Parkinson Foundation; Omeros Corporation; Parkinson Study Group; Pfizer; Prothena Biosciences Inc; Psyadon Pharmaceuticals, Inc; St. Jude Medical; Teva Pharmaceutical Industries Ltd. He has served as a consultant or as an advisory committee member for: Adamas Pharmaceuticals, Inc; Allergan, Inc; Auspex Pharmaceuticals, Inc and Teva Pharmaceutical Industries Ltd. J Jankovic has received royalties from: Cambridge; Elsevier; Future Science Group; Hodder Arnold; Lippincott Williams and Wilkins and Wiley-Blackwell. He is on the editorial boards for: Medlink: Neurology; Expert Review of Neurotherapeutics; Neurology in Clinical Practice; The Botulinum Journal; PeerJ; Therapeutic Advances in Neurological Disorders; Neurotherapeutics; Tremor and Other Hyperkinetic Movements; Journal of Parkinson’s Disease and UpToDate. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed at-risk population. Disease modification by preventing the accumulation of the toxic α-synuclein is now a reachable goal. It remains to be seen, however, whether such therapeutic strategy will translate into safe and effective disease-modifying therapy.