Wednesday, 24 December 2014

The need for better treatments for spasticity

Vermersch P. MObility ImproVEment with spasticity in multiple sclerosis in Europe: the MOVE 1 EU study.Neurodegener Dis Manag. 2014 Dec;4(6):407-415.
SUMMARY  Aim: using a protocol similar to that of the MOVE 1 study in Germany, the multicenter, observational MOVE 1 EU study examined the burden of multiple sclerosis (MS)-related spasticity in other EU countries (Belgium, Finland, France, Ireland, Norway, Poland and Portugal). Materials & Methods: A 12-month retrospective chart documentation was combined with questionnaires for physicians and patients at the time of enrollment. A total of 281 patients from neurology departments and MS units formed the per protocol population. 
Results: in most patients, MS spasticity frequently restricted daily activities and caused some/moderate problems in EQ-5D subdomains of mobility, usual activities and pain/discomfort. Overall, 48% of physicians and 34% of patients were at least partly dissatisfied with the effectiveness of available pharmacotherapy options for MS spasticity. 
Conclusion: Results of the MOVE 1 Germany and MOVE 1 EU studies are aligned and highlight the need to optimize the therapeutic management of patients with MS spasticity across Europe so as to improve their overall well-being and quality of life.

This survey shows that you need better treatment or treatment strategies for the treatment of spasticity.

CoI Please look at the 2014 Advent Calendar

Remyelination with Citicoline

Skripuletz T, Manzel A, Gropengießer K, Schäfer N, Gudi V, Singh V, Salinas Tejedor L, Jörg S, Hammer A, Voss E, Vulinovic F, Degen D, Wolf R, Lee D, Pul R, Moharregh-Khiabani D, Baumgärtner W, Gold R, Linker RA, Stangel M. Pivotal role of choline metabolites in remyelination. Brain. 2014 Dec. pii: awu358. [Epub ahead of print]

Neuroprotective approaches for central nervous system regeneration have not been successful in clinical practice so far and compounds that enhance remyelination are still not available for patients with multiple sclerosis. The objective of this study was to determine potential regenerative effects of the substance cytidine-5'-diphospho (CDP)-choline in two different mouse animal models of multiple sclerosis. The effects of exogenously applied CDP-choline were tested in mouse myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. In addition, the cuprizone-induced mouse model of de- and remyelination was used to specifically test the hypothesis that CDP-choline directly increases remyelination. We found that CDP-choline ameliorated the disease course of experimental autoimmune encephalomyelitis and exerted beneficial effects on myelin, oligodendrocytes and axons. After cuprizone-induced demyelination, CDP-choline effectively enhanced myelin regeneration and reversed motor coordination deficits. The increased remyelination arose from an increase in the numbers of proliferating oligodendrocyte precursor cells and oligodendrocytes. Further in vitro studies suggest that this process is regulated by protein kinase C. We thus identified a new mechanism to enhance central nervous system remyelination via the choline pathway. Due to its regenerative action combined with an excellent safety profile, CDP-choline could become a promising substance for patients with multiple sclerosis as an add-on therapy.

Citicoline (CDP-choline; cytidine 5'-diphosphocholine) is an important intermediate in the biosynthesis of cell membrane phospholipids. Citicoline serves as a choline donor in the biosynthetic pathways of acetylcholine and neuronal membrane phospholipids, mainly phosphatidylcholine. This study suggests that it can promote remyelination. In EAE  there was an anti-inflammatory effect and less disease was accumulated and faster remyelination occurred in a chemical demyelination model. This molecule has been implicated as a neuroprotectant in other studies so could be a new tool to promote repair. But can this be translated.

Advent Calendar-24

So this is it for our drug development programme, we started with an idea and a number of years later we are ready to try treat  multiple sclerosis.

So you have your trial design and you eligibility criteria and you are ready for doing a phase II study in people with MS. This is to test the efficacy of the drug and also to check safety.
If (let's be hopeful and say when) this works then we are ready for the next step, so we will have to raise funds to do the pivotal Phase III trials.

This is the basis process that pharma will do to develop drugs to you. This is the end of our story so far.

When will ours be ready to go...Sometime in early 2015

CoI We are developing a drug for symptom control