Category Archives: CBD

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.

 

WSJ Article About Tau Researcher

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This post is about tau protein. Tau is the protein involved in PSP, CBD, and Alzheimer’s Disease.

This Wall Street Journal article is on researcher Claude Wischik, tau protein, and Alzheimer’s research. Dr. Wischik “has long backed a minority view: that a protein in the brain called tau – not plaque – is largely responsible” for Alzheimer’s. Since this article is from the WSJ, there is an investment focus to part of the article.

For me, the most interesting part of the article was one sentence in parentheses. Dr. Wischik founded a company called TauRX Pharmaceuticals. They did a small study of a tau drug, called Rember, in Alzheimer’s patients. They never published the full results. “(Dr. Wischik says it didn’t to protect the company’s commercial interests.)”

There’s also a 5-minute video that focuses on the tau vs. amyloid debate. (This is sometimes called the “tauists vs. the BAPtists.” BAP = beta amyloid protein.) I’d recommend watching the video and then reviewing the article, if you are still interested.

Robin

5-minute video (after 15-second ad) on tau tangles, why Dr. Wischik focused on tau, why the rest of the community focused on amyloid, and what else is going on besides protein accumulation:

http://online.wsj.com/article/SB1000087 … bs%3Dvideo

http://online.wsj.com/article/SB1000087 … %3Darticle
(I was able to view the full article this morning though it’s listed as “subscriber content only.” Probably this website error will be fixed soon)

HEALTH INDUSTRY
Updated November 9, 2012
Wall Street Journal

An Outcast Among Peers Gains Traction on Alzheimer’s Cure
By Jeanne Whalen

Some people collect stamps, others vintage cars. As a young Ph.D. student at Cambridge University in the 1980s, Claude Wischik was on a mission to collect brains. …

Big news in PSP community – genetics study finally published!

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This is big news for the PSP (and CBD) community: the genetics study finally got published yesterday in the journal Nature Genetics. (I think Dr. Schellenberg had gotten side-tracked on some Alzheimer’s-related research, so it’s good to see the research finally seeing the light of day.) The data published are limited to PSP.

The CurePSP press release talks about “three new genes linked to” PSP being identified. In Dr. Schellenberg’s November 2009 update (see earlier blog post), he talked about four new genes being identified. The difference is that we’ve known about MAPT – the tau gene – being associated with PSP for a long time. (Dr. Irene Litvan did that research.) Dr. Schellenberg and other researchers found a second variant of MAPT that is also associated with PSP. So that’s how we get to four new variants.

This research is made possible through brain donations from those with PSP. Dr. Schellenberg said in November 2009 that 1212 PSP brains were donated and included in the first go-round with a target of 1000 more brains to be included in a replication study. As it worked out, the data published yesterday were based on:

* 1,114 PSP cases – stage 1
* 1,051 PSP cases – stage 2

At least four local support group members were included in stage 1 (including my father). And four were included in stage 2.

Many more brains have been donated in the last 18 months, and that tissue will be part of future studies.

Perhaps the next steps are developing tests that look for these genetic variations in the living. And developing treatments based on this new knowledge. Certainly other work into finding the cause and cure for PSP (and CBD) will take advantage of this new data as well.

I’ve copied the understandable CurePSP press release below. In another post, I’ll copy the abstract of the Nature Genetics paper, authored by the PSP Genetics Study Group. The authors are all the big names in PSP genetics research. I’m not entirely sure but I think it’s a disappointment that this is published as a letter rather than as an a research article; I believe that letters are not subject to the same sort of peer review as the articles. Still, it’s great that the research has been published.

Robin

CurePSP press release:

CurePSP-funded Study Identifies Three New Genes Linked to Progressive Supranuclear Palsy

TIMONIUM, Maryland, June 19, 2011 – An international team of researchers led by Gerard D. Schellenberg, PhD, a member of the CurePSP Genetics Consortium and professor of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania, has identified three new genes that can increase the risk of people developing Progressive Supranuclear Palsy (PSP).

PSP is a rare neurodegenerative brain disease, similar to Parkinson’s disease, which causes severe disability by destroying parts of cells that allow the brain to function normally. While PSP has underlying biological similarities to Alzheimer’s disease, a disease which primarily affects memory, PSP impacts a person’s physical movement and bodily functions. PSP leads to progressive decline in patients – there is no known cause or cure.

The study found significant genetic signals associated with PSP risk at several genes including STX6, EIF2AK3, MOBP, and confirmed two variants within MAPT (the tau gene), which influences tau expression in the brain. The identified genes encode proteins for vesicle functioning, protein folding, and myelin – critical functions that help the brain operate normally. The findings appear in the current issue of Nature Genetics (NG-A29596R1).

“The CurePSP Genetics Program and this genome-wide association study is perhaps the single most important research project to date funded by the Foundation,” said Dr. Richard Gordon Zyne, President-CEO of CurePSP. “The study, which is a product of our genetics program, is significant because it will help researchers better understand the factors that lead to the development of PSP.”

Understanding the cause of the disease is a critical step in the battle against PSP, and may lead to the creation of tools for early diagnosis, preventative drug treatments, and eventually, a cure.

The study was supported by grants from the Foundation for PSP | CBD and Related Brain Diseases (CurePSP), the Peebler PSP Research Foundation, and the National Institutes of Health (NIH)’s National Institute on Aging (NIA) and the National Institute of Mental Health (NIMH), among other organizations.