If you are interested in the quality of laboratory-based research you should read this article.
Baker et al. Mult Scler. 2011 Mar 3. [Epub ahead of print]
“It is great that the lab-based scientists have started doing their experiments to the same standards of quality required of clinical trials.”
COI: David Baker and Sandra Amor are members of our group.
At last the Sativex study results in print.
“Most neurologists don’t like the study design used in this trial, i.e. an enrichment design in which only the responders from the first phase were included in the second comparative phase to show the drug worked. It is important to remember that it is impossible to blind a trial that is testing cannabinoids as they have psycho-active effects. The reality of symptomatic therapies is that we always use them in this way in the clinic; i.e. we give someone a therapeutic trial and if they don’t respond or they develop intolerable side effects we stop the drug.”
Novotna et al. Eur J Neurol. 2011 Mar 1. doi: 10.1111/j.1468-1331.2010.03328.x. [Epub ahead of print]
Sativex Trial Design
This study shows that repeated injections of botulinum toxin into the detrusor muscle* of the bladder in PwMS, who have refractory over-activity of their bladders, leads to a consistent effect on bladder control and, importantly, results in sustained improvement in quality of life.
* “The detrusor muscle is the balloon-like muscle that relaxes when the bladder is filling and contracts when the bladder is emptying. In MS the detrusor muscle is typically overactive leading to a small contracted bladders (low volume or small balloon) that is irritable. The combination of these effects results in patients complaining of urinary frequency and urgency. Multiple botulinum toxin injections into the detrusor muscle relaxes the muscle, which increases the volume of the bladder and reduces the irritability of the bladder. As the injections into the bladder wall have to be done using a flexible scope under direct visual guidance the procedure and treatment are relatively expensive.”
Khan & Fowler et al. J Urol. 2011 Apr;185(4):1344-9. Epub 2011 Feb 22.
I used to work with Professor Clare Fowler who led this study; she was a very caring and thoughtful neuro-urologist who pioneered this treatment. One of my MS heroes!
A new trial design for doing neuroprotective MS clinical studies. The investigators propose using an adaptive design in that the trial changes over time so that only the winners (2 out of 4 of the active arms) in the first phase get through the final or definitive arm of the study.
“This study design is very appealing, but unfortunately it may go down poorly in the patient community. The study will take about 7 years to complete; 2 years to recruit, 2 years to do phase 1 and 3 years for the phase 2 arm of the study. In my opinion 7 years is simply too long in the life of someone with progressive MS to get an answer. We clearly need better and quicker trials for testing neuroprotective drugs in progressive MS.”
Friede et al. Stat Med. 2011 Feb 22. doi: 10.1002/sim.4202. [Epub ahead of print]
COI: I sit on the steering committee of the UK MS Society’s Clinical Trial Network that commissioned the work to design this study.
This study shows that in an animal model of advanced secondary progressive MS the drug FTY720 or Fingolimod is not capable of preventing or delaying the progression of disability independently of its effects on inflammation. The investigators allowed the animals to enter the progressive phase of the disease, before shutting down autoimmune driven inflammation by inducing immune tolerance (a fancy word for switching off the immune system’s attack on the brain and spinal cord) before starting the therapy.
“Does this mean that Fingolimod is not neuroprotective? No it does not, it only shows that in this particular setting that Fingolimod is not effective. Can I remind you that modifying this phase of the disease course remains the holy grail in MS therapeutics, i.e. modifying the progressive phase of MS after inflammation has been switched off with potent anti-inflammatory therapies. This is why we are concentrating so much of or time and effort on developing neuroprotective treatments.”
Al-Izki et al. Mult Scler. 2011 Apr 1. [Epub ahead of print]
Declaration of a conflict of interest: this study was supported by Novartis and it was done by our group.
When MS causes a new lesion in the brain it leaves behind a scar ~80% of the time. The scar may become a black-hole which indicates loss of underlying tissues. The lesions that cause black holes are considered to be more destructive than lesions than don’t leave behind black-holes.
“This study shows that interferon-beta, is as likely as glatiramer acetate, to prevent lesions from turning into black holes. This would indicate that both these DMTs affect the evolution of lesions and reduce their effect on brain tissue; this data would support both these drugs as having some neuroprotective effect.”
Exercise therapy may have a positive effect on MS-related fatigue, however, the findings of a systematic review show the impact of exercise can be highly variable.
“I think the problem with in the field of fatigue is that we still don’t know how to measure fatigue or even characterise it; for example mental/cognitive vs. physical (exercised-induced or temperature-sensitivity) or fatigue related to low mood or sleep deprivation. Sleep-deprivation is a common problem in PwMS and relates to many issues that are often relatively easy to manage, for example nocturnal spasms, pain and nocturia (getting-up to go to the toilet due to bladder problems). I think it is time we sorted this mess out.”
Andreasen A, et al. Mult Scler. 2011 Apr 5. [Epub ahead of print]
Could we use disease-activity free status to determine the effectiveness of new MS disease-modifying therapies? It may make it easier to do head-to-head studies.
Please see the following links:
Coles et al. Lancet Neurol. 2011 Apr;10(4):338-48.
Giovannoni et al. Lancet Neurol. 2011 Apr;10(4):329-337.
Why can’t patients improve on disease modifying therapies?
It looks as if the mitochondria are the target in focal axonal damage in EAE, the animal model of MS.