Deans' stroke musings: Potential Remyelinating Drug Meets Endpoint in Clinical Trial

Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Thursday, April 21, 2016

Potential Remyelinating Drug Meets Endpoint in Clinical Trial

First question. Does stroke cause demyelination? A fucking simple question that I have not been able to find out. If we had a stroke strategy and database of research trials and stroke protocols we could find out this answer. But we don't because we have fucking failures of stroke associations.
http://www.medpagetoday.com/MeetingCoverage/AAN/57458?xid=nl_mpt_DHE_2016-04-21&eun=g424561d0r
Clemastine, the antihistamine sold worldwide as Tavist, passed an initial clinical test as an agent to promote remyelination of nerves damaged in multiple sclerosis, a researcher reported here.
In a placebo-controlled phase II trial, MS patients with chronic optic neuropathy showed improvements in visual evoked potential latency (VEPL) and a trend toward better low-contrast visual acuity when treated with clemastine, said Ari Green, MD, of the University of California San Francisco.
From baseline VEPL values of 126 to 129 ms, patients treated for 2 to 3 months with clemastine at 4 mg twice daily in the crossover study showed a mean reduction of 1.9 ms (95% CI 0.5-2.9) compared with placebo treatment, he reported here at the American Academy of Neurology annual meeting.
Low contrast visual acuity ratings, which averaged 23 at baseline, improved by 2.5 points with clemastine versus 1.7 on placebo (P=0.09).
Patients in the study were randomized to a 3-month treatment period with either clemastine or placebo, followed by a switch to the other treatment for 2 months.
Clemastine did have one significant adverse effect, however: worsened fatigue ratings, Green said. This was expected as somnolence is a known side effect of the antihistamine class to which the drug belongs. Clemastine treatment was associated with mild worsening of fatigue on the multidimensional assessment of fatigue (P=0.017).
It's potentially a serious drawback for an MS treatment, since fatigue is already one of the condition's most debilitating symptoms. For this reason and others -- notably, that clemastine achieves relatively low saturation at the presumed target receptor -- Green told MedPage Today that clemastine would probably not end up as a recommended treatment for progressive MS.
Rather, he suggested, it points the way toward other agents with better pharmacodynamics that leave out the antihistamine effects and focus more specifically on remyelination.
The rationale for clemastine in this condition is that, in an in vitro screening study for drugs that promote oligodendrocyte proliferation -- these cells being critical to myelin formation -- clemastine came out on top.
A leading theory of progressive MS (for which there are no treatments currently recognized as substantially effective) is that the demyelination at the root of functional disability results from a failure of oligodendrocyte activity. Hence, a number of different research lines are currently focusing on approaches that boost this activity.
For the current study, Green and colleagues picked chronic optic neuropathy (as distinct from optic neuritis, an acute condition that also accompanies MS) as the condition to examine because a remyelinating effect could potentially be detected in a small study lasting a few months. That would not likely be possible for MS-type disability, Green said -- effects on walking ability, for example, would require longer treatment and more patients, and his group had no industry support for this research and hence insufficient funding for such a trial.
The current study did include the Expanded Disability Status Scale, the 6-minute walk test, and other MS functional outcomes as secondary endpoints. Green did not report those results here and would not talk about them with MedPage Today, citing a potential journal publication.
Anthony Reder, MD, of the University of Chicago, who was not involved with the study, said he thought the study was important in leading toward a treatment for progressive MS.
He marveled that a "cheap drug" could have such a notable effect in a short-duration study, and said he saw potential for it as an add-on to other therapies.
He agreed that clemastine has drawbacks, but called it "a clue" toward a workable remyelination approach.
And Edward Fine, MD, a neurophysiologist at the University of Buffalo in New York, complimented the researchers on the elegant study design, saying that VEPL was "rock solid" as measure of nerve function and marker of myelination.