Therapeutic options for Progressive Supranuclear Palsy including investigational drugs

ABSTRACT

Introduction: Progressive Supranuclear Palsy (PSP) is the most common atypical parkinsonian syndrome. PSP presents clinically with various phenotypes. The typical clinical findings of PSP-Richardson, the classical clinical phenotype include: vertical supranuclear gaze palsy, early postural instability and falls, symmetric akineto-rigid parkinsonism, early dysarthria and dysphagia and frontal cognitive deficits

Areas covered: In this article, we discuss the most important therapeutic targets for PSP patients based on the hypothesized pathogenesis of the disease, review undergoing disease modifying clinical experimental therapeutic trials and summarize common symptomatic and palliative approaches.

Expert opinion: Major experimental disease modifying therapeutic trials in PSP have included glycogen synthase kinase (GSK) 3 inhibitors, microtubule stabilizers, antioxidants and glutamatergic inhibitors. Tau antibodies, microglial inhibitors, anti-inflammatories, PERK modulators, Rho kinase inhibitors, CDK5 inhibitors, anti-sense oligonucleotides, and calpain inhibitors have shown promising effects in transgenic animal models of tauopathies and are being translated into PSP therapeutic trials. Unfortunately, most of the current symptomatic therapeutic approaches are based on small double-blind, placebo control studies, or open trials. It is expected that future symptomatic therapeutic trials will be methodologically robust including larger, well-designed double-blind, placebo, controlled design.

KEYWORDS:

• Progressive Supranuclear Palsy
• management
• therapy

Article highlights

• At present, there are no disease modifying therapies for PSP patients but several promising targets have been identified based on the wide range of potential mechanisms of neurodegeneration that may be involved. It will be necessary to determine which one/s are the most efficacious. It is possible that more than one therapeutic approach might be needed.

• Tau antibodies, glycogen synthase kinase (GSK) 3 inhibitors, microtubule stabilizers, microglial inhibitors, anti-inflammatories, antioxidants, PERK modulators, Rho kinase inhibitors, CDK5 inhibitors, anti-sense oligonucleotides, and calpain inhibitors are the most promising disease modifying therapeutic agents for PSP patients.

• Most of the current symptomatic approaches are based on small double-blind, placebo controlled studies, or open trials and further evaluation by rigorous double-blind, placebo, controlled therapeutic trials are needed.

• Symptomatic therapeutic strategies should cover the main sources of disability for PSP patients including falls and postural instability, gait disturbances, parkinsonism, behavioral and cognitive disturbances, pseudo-bulbar and eye movement abnormalities, malnutrition, and weight loss.

• A multidisciplinary team including movement disorder specialists, behavioral neurologists, a rehab team that consist of physical, occupational and speech therapists, neuropsychologist, psychiatrist and a social worker is necessary to provide the best approaches for treatment of various symptoms of PSP patients.

This box summarizes key points contained in the article.

Declaration of interest

I Litvan has been a member of the Biogen, Bristol Meyers Squibb and Lundbeck advisory boards and is a member of the Biotie/Parkinson Study Group Medical Advisory Board. She is an investigator in NIH grants: 5P50 AG005131-31, 5T35HL007491, 1U01NS086659 and 1U54NS09089-01; Parkinson Study Group, Michael J Fox Foundation, Abbvie, AVID Pharmaceuticals, C2N Diagnostics and Bristol-Meyers Squibb. She receives her salary from the University of California San Diego. 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.

Additional information

Funding

This paper was not funded