Category Archives: PSP

Easy Trick to Distinguish PSP from PD

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Tim Rittman, a clinical research fellow in neurology in the UK, recently posted to The PSP Association’s blog about his recent paper on using cognitive testing to differentiate Parkinson’s Disease (PD) and progressive supranuclear palsy (PSP).  Here’s a link to his blog post:

www.pspassociation.org.uk/2013/01/easy-trick-to-distinguish-psp-from-parkinsons-disease/#more-6112

The full post is copied below.

Robin

——————–

Tim Rittman
Post to The PSP Association’s Blog

I’m pleased the JNNP have published my paper on cognitive testing in Parkinson’s disease (PD) and two rarer but important diseases that can be confused, Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD), though a little surprised no one had done the study before now. The headlines are:

  • a short test of verbal fluency distinguishes extremely well between Parkinson’s disease and Progressive Supranuclear Palsy
  • it’s not so useful for distinguishing Parkinson’s disease from Corticobasal Degeneration, or between Progressive Supranuclear Palsy and Corticobasal Degeneration
  • the ACE-R test changes over time in Parkinson’s and Corticobasal Degeneration, but not so much in Progressive Supranuclear Palsy

If you want more details, either read the paper or get in touch! Even though it’s not the main chunk of my thesis, I enjoyed writing this paper. It gets to the heart of a challenging clinical problem (and deals with the fun part of being a neurologist!), that of making the correct diagnosis in similar diseases. It uses relatively simple tools, in the Revised Addenbrooke’s Cognitive Examination and verbal fluency scores, so should apply to most clinic or hospital situations.

Parkinson’s can be a tough disease to deal with, but usually responds well to treatment for many years. Giving a diagnosis of PSP or CBD has much great implications for patients and relatives in terms of the lack or treatment response, shorter prognosis, and challenging cognitive and motor symptoms.

To those who know PSP and CBD well, there is nothing particularly surprising in our results, although the high significance levels and good performance of the tests will hopefully give some confidence in existing knowledge. My hope is this will raise awareness among those less familiar with the disorders, and enable earlier recognition of PSP and CBD. JNNP has a wide readership among clinicians, so I’m really pleased they’ve published it. I may be optimistic, but if anyone finds the paper useful because they’re struggling with differential diagnosis, then I’d love to hear from you!

Bad News about Both PSP/CBD Experimental Trials in 2012

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I wanted to be sure everyone saw the very bad news that came out in 2012:  the two experimental drug trials in PSP — Davunetide and Nypta.

Hopefully the search will continue for a medication that can slow the progression of PSP and CBD — both tauopathies.  And hopefully cures can eventually be found for these diseases.

Adam Boxer, MD, the neurologist at UCSF’s Memory & Aging Clinic and the principal investigator of the Davunetide trial, has spoken forcefully in the past about pharmaceutical companies using PSP — rather than Alzheimer’s Disease — as the testing ground for tau-modifying agents.  I hope the failure of Davunetide doesn’t mean that Dr. Boxer’s theory has been disproven.

A small number of people in our local support group participated in the Davunetide trial; UCSF was the lead institution.  (A total of 313 people participated worldwide.)  And a couple of our group members participated in the pilot trial of Davunetide done at UCSF in PSP, CBD, and FTD.  I don’t believe anyone in our group participated in the Nypta trial.  (UCLA was the nearest institution participating.)  I would like to thank those who participated.  Without their sacrifice, we would not have known whether this medication was effective or not.

Anecdotal evidence in at least one local participant suggested
Davunetide was effective.  I guess that was placebo effect?

The manufacturer of Davunetide, Allon Therapeutics, had a phone call with investors the day the results were announced in mid-December 2012. Janet Edmunson, the chair of CurePSP, listened to a recording of the call.  One point that she passed on — that was not in the press release — was that perhaps not enough of the medication was given. Would a higher dose work?  Allon said the results are being further analyzed to “determine if there is any evidence of an effect or explanation for the absence of an effect.”

Apparently, the bad news about the worldwide Nypta trial came out in early 2012.  UCLA was the nearest participating medical center.  I don’t think Dr. Boxer mentioned this failed trial at the October symposium.  Noscira, the manufacturer of Nypta (tideglusib), said that the experimental medication failed in PSP but a trial in Alzheimer’s Disease would continue in 2012.  No results of that have been announced yet.

This seems to be the path of most medical research — some steps
forward and lots of steps back (or sideways).  We’ll just have to keep hoping for a breakthrough as the researchers continue to plod away.

If you’d like to read the details on the bad news, check out:

Allon Therapeutics press release regarding Davunetide
www.allontherapeutics.com/2012/12/allon-announces-psp-clinical-trial-results/
Excerpt:  “The study had co-primary outcome measures: the Progressive Supranuclear Palsy Rating Scale (PSPRS), and the Schwab and England Activities of Daily Living (SEADL).  Data analysis failed to detect an effect on either the PSPRS or the SEADL.”

Noscira CEO letter regarding Nypta (tideglusib)
www.noscira.com/noscira.cfm?idIdioma=2&idArticulo=97

Robin

“3 Questions to Ask About Assisted Living Memory Care Communities”

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This post will be of interest to those who may be looking at memory care facilities for their loved ones with dementia.  (This is the name given to care facilities that specialize in caring for those with dementia.  Since the most common dementia is Alzheimer’s Disease, and AD has prominent memory issues, these facilities use the word “memory care” rather than “dementia care.”)

Steven Russell, BSN’s treasurer, recently came across a column in the Huffington Post in December 2011 on three broad questions to ask memory care facilities:

1- how good is the quality of care?
2- how rich and individualized is the activity program?
3- how well-designed and maintained is the place?

For each broad question, there are many sub-questions provided.  The article was written by Marguerite Manteau-Rao, the Palo Alto-based social worker who is a long-time BSN friend.

Here’s a link to the article:

www.huffingtonpost.com/marguerite-manteaurao/memory-care-communities_b_1155043.html

3 Questions to Ask About Assisted Living Memory Care Communities
by Marguerite Manteau-Rao, LCSW
Huffington Post
Posted 12/21/11

Robin

 

 

Davunetide Study in PSP – Disappointing Results

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Tim Rittman, a clinical research fellow in neurology in the UK, recently posted to The PSP Association’s blog about the disappointing results in the davunetide clinical trial in PSP.  (UCSF was the lead institution in investigating this experimental drug.)

Here’s a link to the blog post:

www.pspassociation.org.uk/2013/01/davunetide-in-psp-disappointing-results/#more-6110

And the post is copied in full below.

Let’s hope there’s better luck next time!

Robin
————————————–

Tim Rittman
Post to The PSP Association’s Blog

Anyone looking after someone with dementia, particularly Progressive Supranuclear Palsy (PSP), can not fail to be disappointed by the recent failure of Davunetide in a phase III trial. Allon therapeutics announced just before Christmas that no clinical endpoint had shown improvement.

Whilst this is one in a growing line of failures for disease modifying treatment in dementia, some would argue Davunetide had more chance than its predecessors. Firstly, it targeted the tau protein, which builds up in and around the neurons of people with PSP. No doubt Allon were hoping that it would work, and then be taken in to trials of Alzheimer’s disease where tau is also found. Most previous drugs trials in Alzheimer’s disease have focused on beta-amyloid, another protein that can build up in the brain, but which is less certain to be a central part of the disease process and may be a tombstone of other events (for example see here). In PSP there is no amyloid, so targeting tau, and only tau, was supposed to work.

Most disappointing is that none of the secondary or exploratory endpoints showed any signs of change, although we are not told what these were. When designing a drug study, it is usual to pick hard clinical measures as a primary endpoint. I would have been hugely surprised if the primary endpoints had changed, given that the disease process in PSP is rather fast, and slowing it down once symptoms have developed is like stopping an out-of-control roller coaster. But perhaps Davunetide could have at least made a few dents in other measures, hinting that the approach to target tau was correct. I’m afraid we’re not given that comfort.

Does that mean it’s all been worthless? No. Each clinical trial has useful data in it, even if that data is not what we would wish to see. I do hope the full results see the light of day. Those who know me well also know I do not have a soft spot for drug companies. But I feel genuinely sorry for Allon. They are a relatively small company and this (commercial) failure has come as a big blow both in share price and job losses. I’m not sure whether the company can survive. If Allon does go under, I wonder what will happen to the data. The press release commented on further investigation as to why the drug didn’t work, my hope is this will be in the open and not behind closed doors under the defence of ‘commercial interests’. I’d love to get my hands on it if I could!

It is natural to pick on tau and beta-amyloid as targets for slowing down the disease. Both proteins are easily seen under even the simplest microscope, and have a long track record in lab and animal experiments. But we need to be more savvy about how we develop drugs in the future, targeting multiple pathways and developing drugs that target disease mechanisms we can’t see. This means new disease measures and new drug discovery techniques (that’s a whole different blog!). I only hope we have some encouraging news before the pharma industry turns its back on dementia completely.

 

Allon announces PSP clinical trial results (davunetide)

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This is very disappointing news out of Allon Therapeutics, a Canadian company paying for a trial of davunetide in progressive supranuclear palsy (PSP). I’ll see if I can find out more details. UCSF was the lead investigator of the study.

Robin

http://www.allontherapeutics.com/2012/12/allon-announces-psp-clinical-trial-results/

Allon announces PSP clinical trial results
December 18, 2012

VANCOUVER, B.C. — Allon Therapeutics Inc. (TSX: NPC) announced today that its pivotal clinical trial evaluating its lead product candidate davunetide as a treatment for progressive supranuclear palsy (PSP) failed to demonstrate efficacy in this population.

The study had co-primary outcome measures: the Progressive Supranuclear Palsy Rating Scale (PSPRS), and the Schwab and England Activities of Daily Living (SEADL). Data analysis failed to detect an effect on either the PSPRS or the SEADL.

The study also examined a series of secondary and exploratory endpoints. There was no evidence of a drug effect on these secondary or exploratory endpoints in the pre-specified analysis. The Company will undertake further analysis to determine if there is any evidence of an effect or explanation for the absence of an effect.