Thursday, 21 August 2014

A Prostate Cancer Drug maybe the answer to remyelination

IRX4204, a retinoid X receptor-agonist studied for prostate cancer, also promotes differentiation of oligodendrocytes and the formation of regulatory T cells and inhibits the formation of TH 17 cells in vitro, suggesting its potential for myelin repair in multiple sclerosis. In mouse models of MS, mice given IRX4204 had better EAE scores 13 days after treatment than those that were not given the drug. IRX4204 is highly specific to RXR and does not transactivate the retinoic acid receptors (RARs), avoiding some of the potential side effects associated with RAR agonists. Martin Sanders, MD, the chairman and chief executive officer of Io Therapeutics, a small company based in Santa Ana, CA, that owns the drug and is exploring its potential applications.

“It's already been used in humans — and that's huge,” Dr. Sanders said. “We have treated patients for up to 20 months and they've tolerated the drug well.

Neurology Today: 3 July 2014 - Volume 14 - Issue 13 - p 22-23 doi: 10.1097/01.NT.0000452276.24201.20.

This is an extension of Robin Franklin's groups finding that RXR receptor is expressed during remyelination. They also found that getting rid of RXR-gamma prevented oligodendrocyte multiplication in culture, showing that RXR is important in remyelination.

As a next step the Sanders group plan to test this in another animal model of remyelination to test whether the findings hold up. But if successful, there is no reason why they shouldn't move ahead to a Phase II clinical trial in MS patients. It has already been found to be safe in patients with prostate cancer; so there is no need to carry out a Phase I safety study in humans (Hooray!). 

PS: as it also reduces PSA levels, it may be a win win scenario for the men!

Barts MS Team away day - reporting back

Last Thursday we held our first team away day for over 5 years. When planning the day it was very clear that we had a mountain of topics to get through so getting everyone away from the distractions of Whitechapel was important. So, we ended up on a boat, in Regents Park, on a vintage red bus and then back on the canal. 

Before we could start discussing the huge agenda, we had to loosen up a bit. We started our team building with The Marshmallow Challenge to help us think innovatively, creatively and collaboratively.

We then used personas to help us imagine new goals for the team and inspire us to 'think big'.

But this wasn’t just a bit of fun, we really considered how to make (the more plausible) ambitions a reality.

Some of the big messages to come out of the day been around improving communication within the group, consolidating the ‘Barts MS’ brand that encompasses all of our initiatives and ensuring that our clinical service, research projects and public engagement efforts are inherently linked.

We also spent time considering individuals roles within the group and how peoples day-to-day work can feed into these main ambitions. Some of the new ideas to come out of the day involved:

    Innovative funding ideas
    Improving our MS Nurse service
    Our move to the new Royal London Hospital building and the potential for new clinics
    Barts MS within UCLP and QMUL
    This blog! (you might notice some new authors - please be gentle)
    Education via Centre of the Cell
    The Future of the MS Research Day
    New research avenues
    Operational procedures within the group

Apart from that, there was a lot of nitty gritty discussed that will ultimately make us a better functioning team. We hope you will see the benefits of the day through our work and in the coming years. And on top of all that, we even got a team selfie!

Sacre Bleu ProfG est dans le Monde

Actually its ProfG down under in the News about his recent paper.....this has helped get more info to support the Charcot Project....Merci.

Inflammatory genes in neurodegeneration

Durrenberger PF, Fernando FS, Kashefi SN, Bonnert TP, Seilhean D, Nait-Oumesmar B, Schmitt A, Gebicke-Haerter PJ, Falkai P, Gr├╝nblatt E, Palkovits M, Arzberger T, Kretzschmar H, Dexter DT, Reynolds R. Common mechanisms in neurodegeneration and neuroinflammation: a BrainNet Europe gene expression microarray study. J Neural Transm. 2014 Aug 13. [Epub ahead of print]

Neurodegenerative diseases of the central nervous system are characterized by pathogenetic cellular and molecular changes in specific areas of the brain that lead to the dysfunction and/or loss of explicit neuronal populations. Despite exhibiting different clinical profiles and selective neuronal loss, common features such as abnormal protein deposition, dysfunctional cellular transport, mitochondrial deficits, glutamate excitotoxicity, iron accumulation and inflammation are observed in many neurodegenerative disorders, suggesting converging pathways of neurodegeneration. We have generated comparative genome-wide gene expression data, using the Illumina HumanRef 8 Beadchip, for Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, Parkinson's disease, and schizophrenia using an extensive cohort (n = 113) of well-characterized post-mortem brain tissues. The analysis of whole-genome expression patterns across these major disorders offers an outstanding opportunity not only to look into exclusive disease-specific changes, but more importantly to look for potential common molecular pathogenic mechanisms. Surprisingly, no dysregulated gene that passed our selection criteria was found in common across all six diseases. However, 61 dysregulated genes were shared when comparing five and four diseases. The few genes highlighted by our direct gene comparison analysis hint toward common neuronal homeostatic, survival and synaptic plasticity pathways. In addition, we report changes to several inflammation-related genes in all diseases. This work is supportive of a general role of the innate immune system in the pathogenesis and/or response to neurodegeneration.

This is a massively complex piece of work creating masses of data. However this is the problem with micro array...there can be too much data. If you compare different disease and look at the protein messages going up or down. When looking at all genes there are none/few common to all diseases. Some of them could be associated with enhanced microglial and astrocyte responses. 

Alemtuzumab gets a license in Chile

Is early, effective, induction therapy the new treatment paradigm for MS? #MSBlog #MSResearch

"As promised the following are my slides from yesterday's talk at the SINS meeting in Santiago, Chile. I was asked to talk on alemtuzumab as it has just been given a license in Chile with the same broad indication as that in Europe. Most of the Chilean MSologists I spoke to have a lot of experience using rituximab off-license so I don't see any problems them using alemtuzumab in their current clinical practice."

CoI: multiple