Saturday, 30 April 2016

Neural Stem Cells

Results from the AAN 2016 on neural stem cells 

( (Click)

Here are results from neural stem cell study.

EMA Panel Backs Daclizumab (Zinbryta) for Multiple Sclerosis

Daclizumab is given by self-administered subcutaneous injection once a month.
The humanized monoclonal antibody selectively binds to the high-affinity interleukin-2 receptor subunit (CD25) expressed at abnormally high levels on T cells in patients with MS. Daclizumab offers a targeted mechanism of action that does not cause broad and prolonged immune cell depletion, the company notes in a news release.
According to the CHMP opinion, the benefits of daclizumab include its ability to reduce the annualized relapse rate and risk for disability progression.
The positive CHMP opinion is based on results from two clinical trials. In the DECIDE study, daclizumab 150 mg administered subcutaneously every 4 weeks showed a reduced relapse rate and fewer new lesions on MRI compared with interferon β-1a (Avonex, Biogen) injected intramuscularly weekly.
In the placebo-controlled SELECT study, daclizumab reduced relapse rates and had positive effects on key measures of MS disease activity relative to placebo.
The most common side effects with daclizumab seen in clinical trials are elevations of liver enzymes and hepatic injury, cutaneous events, infections, gastrointestinal disorders, and depression. The CHMP recommends that daclizumab be prescribed by physicians experienced in the management of MS.
For more information on the mechanism of action of daclizumab check Gavin's post ~6 months ago. Personally, I am concerned about yet another drug with a potentially significant secondary autoimmunity problem, however the EMA was happy with daclizumab's risk:benefit profile.

Friday, 29 April 2016

What Does DrK think....Practice what you Preach!

Yesterday's drug delivery, giving six people options where there maybe none...and saving the NHS up to £600,000.
                  Can't wait for the EMA...Cladribine Ready to Go 

For those Health Care professionals and People with MS who may be interested. 

We have updated our Information concerning off-label cladribine use at BartsHealth.

Barts ms clinical guidance for cladribine from BartsMSBlog

There is also information concerning the subcutaneous Administration of Cladribine

Furthermore people enrolling must sign a consent form and be very clear why they are willing to try cladribine. 

We want the best choices for people in our care. 

These may well be the current MS Pharma produced DMT.

However, at BartsMS we are at least willing to try some thing different when these avenues may not be available. 

The documents above show we are prepared to consider Cladribine as an off-label treatment (as we have done it on a similar individual basis, for example, with Rituximab) in situations where (i) eligibility for licensed DMTs cannot be established, or (ii) pwMS, together with the BartsMS team, make an informed decision in favour of off-label treatment rather than a licensed DMT. 

ClinicSpeak: suicide in Swedish MSers

Are you depressed? Please download the Beck Depression Inventory and assess yourself. #ClinicSpeak #MSBlog #MSResearch

"The article below complements my post yesterday on loneliness and social isolation; it confirms that pwMS are at increased risk of both attempted suicide and completed suicide. Men are more successful at committing suicide than women. These are rather depressing figures, but as MS is strongly associated with depression they are not surprising. What can be done about it? All pwMS should be screened for depression and suicidal ideation, or suicidal thoughts, and if they are found to be at risk they should be offered help. Easier said than done? In a recent audit of our service a glaring omission was the patchy screening for depression in our MS clinics. I have included the Beck Depression inventory that you can download and score yourself. If you find you are depressed please see your GP, neurologist or MS CNS."

BACKGROUND AND PURPOSE: Patients with multiple sclerosis (MS) are known to have an elevated suicide risk, but attempted suicide is incompletely investigated. The relation between education level and suicidality has not been investigated in MS patients. Our objective was to estimate attempted suicide and completed suicide risks amongst MS patients.

METHODS: A total of 29 617 Swedish MS patients were identified through the Swedish Patient Register and matched with 296 164 people without MS from the general population. Cox regression analysis estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of MS with attempted and completed suicide, with adjustment for age, sex, education and calendar period.

RESULTS: The adjusted HR for attempted suicide amongst MS patients is 2.18 (95% CI 1.97-2.43) compared with the general population cohort. For completed suicide the HR is 1.87 (95% CI 1.53-2.30). In both groups women are at higher risk of attempting  suicide, whilst men are at higher risk of completing suicide. Education level is inversely associated with completed suicide amongst the non-MS cohort (0.68, 0.51-0.91), but not amongst MS patients (1.10, 0.60-2.04).

CONCLUSION: Multiple sclerosis patients are at higher risk of both attempted and completed suicide. No evidence was found of an inverse association between educational level and risk of completed suicide amongst MS patients. 

Thursday, 28 April 2016

Competition for Canbex

As you may know we are trying to develop a treatment for spasticity. Baclofen is the usual go to drug, but it is not without its problems. One is the Zombie effect because it is very sedating because it is sedative, because it inhibits nerve function making muscle weakness and having cognitive effects. 

It also has a low binding affinity for its target the GABA B receptor. So you need high blood/brain levels for it to work. 

Next the other problem it has a short half life = the time taken for half of the drug to disappear. This means that the drug is gone within 8hours.

This means that it can't get you through the night. Therefore you have to wake up. to dose in the night or you are going to wake up with stiffies...yet stiff legs and hands. 

So you have a peak and a trough in drug levels meaning cogfog to maintain therapy or if you try avoid the cogfog it is an "on" and "off" with the drug working. 

In this study presented at the AAN they have taken baclofen and re-formulated it to give a slow release to avoid the peaks and the troughs but to create a longer half life, so you can have a twice a day pill. In this study they show that the long-life pill is better than placebo but no different from baclofen and it drops the levels of side effects.

So if this drug makes it it this creates competition for our drug, if our drug every makes it. 

Our claim is not that it will work better than current drugs, it is that that it will avoid the side-effects e.g. sedation of current drugs. 

How does it do this? ....Magic?.....You will soon find out.

If you fit the profile and are interested in participating in our trial of VSN16R and can get to...or are willing to go to London (UCL or Barts), Liverpool or Sheffield, you can contact one of the centres (CLICK).

The study will last less than 1 month.