Therapeutic advances and research update in MSA and PSP

This post may be of interest to those wanting to know about what key research in PSP and MSA has taken place in the last few years, and what research is ongoing or recruiting.

This review article on PSP and MSA clinical trials was just published last week.  The article is written for MSA and PSP researchers, explaining how trials since 2013 have been conducted and highlighting priority areas for future therapeutic research.  The lead author is Werner Poewe, MD, an Austrian physician and researcher.  I believe at the most recent Movement Disorder Society meeting in San Diego, he led a discussion with MSA researchers.  Perhaps he reviewed his article at the meeting.

The article notes that an earlier study of riluzole in MSA and PSP proved the feasibility of conducting large controlled trials in these two disorders.  And the study validated disease-specific rating scales for MSA and PSP.  Nearly 800 subjects were enrolled in that study.  The results, published in 2009, were negative for the medication itself.

But that large riluzole study kicked off other trials — two large clinical trials in MSA (rasagiline, rifampicin) and two large clinical trials in PSP (tideglusib, davunetide).  Those four trials failed as well.  The authors describes those trials in detail.

The article lists all of the other trials conducted since 2013 in PSP and MSA, whether results were published or not.  These include a lithium trial in MSA, two droxidopa trials in MSA, a fluoxetine trial in MSA (unpublished), a high-dose CoQ10 trial (2400mg/day) in PSP, and a valproic acid trial in PSP (unpublished).  Unfortunately one rasagiline study in PSP failed to enroll the necessary number of participants.

Though the therapeutic agents being tested in these trials failed, the studies themselves “have made important contributions to our ability to refine designs in future clinical studies targeting these conditions. As a whole they have shown that enrolling sufficient numbers of patients into trials of the less common forms of degenerative parkinsonism is feasible and that this can be accomplished within reasonable time frames.”

The authors note that despite recent trials in PSP and MSA, “there is still a profound lack of symptomatic trials for these disorders.”

The authors state:  “Although autonomic dysfunction is a key driver of disability in MSA, new drugs to treat OH, such as droxidopa, have not been tested in trials specifically enrolling MSA cases only. Likewise, none of the non-pharmacological measures such as exercise-based approaches that are a central part of palliative therapy for patients with MSA or PSP have been tested in properly designed clinical trials.”

The authors call for future research to address two main areas of need:  “improving symptomatic control, independence and well-being of patients by symptomatic interventions, and altering the course of disease by interfering with the mechanisms underlying progressive neurological impairment and disability.”

In case you are interested in exploring the ongoing trials or trials not yet recruiting in MSA and PSP, see the following list:  (If a trial is recruiting, I’ve listed the NIH clinical trial number so that you can look up info on


  • two for droxidopa (one recruiting, NCT02071459, and one isn’t)
  • autologous mesenchymal stem cells (not recruiting)
  • EGCG – a green tea extract (recruiting, NCT02008721)
  • water/peudoephedrine (recruiting, NCT02149901)
  • AFFITOPE – active immunization against alpha-synuclein (recruiting, NCT02270489),
    nebivolol (not recruiting)
  • AZD3241 (the paper says not recruiting but it’s now recruiting, NCT02388295)


  • bone marrow stem cell therapy (ongoing, NCT01824121)
  • TPI-287 (ongoing, NCT02133846)

I think most of you will want to stop reading here.  Below, I’ve provided the abstract.



Movement Disorders. 2015 Jul 30.
Therapeutic advances in multiple system atrophy and progressive supranuclear palsy.
Poewe W, Mahlknecht P, Krismer F.

Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are relentlessly progressive neurodegenerative diseases leading to severe disability and ultimately death within less than 10 y. Despite increasing efforts in basic and clinical research, effective therapies for these atypical parkinsonian disorders are lacking. Although earlier small clinical studies in MSA and PSP mainly focused on symptomatic treatment, advances in the understanding of the molecular underpinnings of these diseases and in the search for biomarkers have paved the way for the first large and well-designed clinical trials aiming at disease modification. Targets of intervention in these trials have included α-synuclein inclusion pathology in the case of MSA and tau-related mechanisms in PSP. Since 2013, four large randomized, placebo-controlled, double-blind disease-modification trials have been completed and published, using rasagiline (MSA), rifampicin (MSA), tideglusib (PSP), or davunetide (PSP). All of these failed to demonstrate signal efficacy with regard to the primary outcome measures. In addition, two randomized, placebo-controlled, double-blind trials have studied the efficacy of droxidopa in the symptomatic treatment of neurogenic orthostatic hypotension, including patients with MSA, with positive results in one trial. This review summarizes the design and the outcomes of these and other smaller trials published since 2013 and attempts to highlight priority areas of future therapeutic research in MSA and PSP.

© 2015 International Parkinson and Movement Disorder Society.

PMID:  26227071