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.
No comments:
Post a Comment