The opening plenary session of this year’s MS Trust Annual Meeting was presented by Pam Macfarlane who welcomed the attendees and explained how far the MS Trust has come over the years. Dr David Bateman then talked about the future of neurology services followed by the Prof. Gavin Giovannoni discussing the future of MS therapy.
A Talk by Dr David Bateman – This presentation centred on improving neurology services and NHS England’s five year plan incorporating five domains, three of which are to improve effectiveness of treatment. There will be specialised commissioning in neurology; epilepsy surgery assessment, surgery for movement disorders, diagnosis of rare neuromuscular disorders and neurogenetics. The CCGs will cover the rest, e.g. all MS services (including disease-modifying therapy, DMT) and all GP referrals (as of April 2015). Multi-specialty Community Providers would become a focal point for a much broader range of care for registered patients. The NHS England community neurology project aims to establish a collaborative that brings together key organisations that together, drive the delivery of person-centred coordinated care for people with neurological conditions.
A Talk by Prof. Giovannoni – This presentation highlighted the near future of treating primary progressive MS (PPMS) with disease modifying treatments. The OPERA I and II trials, presented at the ECTRIMS 2015, found ocrelizumab to be safe and effective in patients. The ORATORIO trial reported positive outcomes for the first time in PPMS patients. However, some have taken the results with caution and suggest the results on disability are modest and would like to see how they translate in the real world. For example, an outstanding question is if the patients were younger, would a more pronounced effect be noticed?
Prof Giovannoni purported the idea that MS should be “rebranded” as a dementia and believes it to be a preventable one too. He described the brain atrophy process as “end stage brain disease” and suggested that the treatment pyramid for MS be flipped as demonstrated by rheumatologists, who have seen a decline in end-stage joint disease having “flipped the treatment pyramid”. For example, an anti-Lingo-1 antibody is being investigated for optic neuritis and results from various clinical trials were reported at the American Academy of Neurology for remyelination and neuroprotection (e.g. phenytoin) (www.mstrust.org.uk). It was suggested that remyelination is not required if the disease is treated early enough. A key message was that MS prevention trials need to happen sooner, referring to Scotland where there is an increase in patients presenting with MS.
The off-patent drug bill was mentioned, which is not favoured by the department of health and the current government. This bill is intended for the repurposing of off-patent drugs, for which there is considerable interest e.g. The MS-STAT study, the CLARITY and CLARITY extension study as well as the ORACLE MS study. These trials could assist rebalance the global inequality of access to DMTs he found during his sabbatical.
Amy Bowen gave an update on the MS Decisions project which was initially started at UCLH (Queens Sq.) in 2006 and the MS Trust fully took it on in 2014. The key project principles are to give patients choice. It gives detailed comparisons of DMTs and can be found at www.mstrust.org.uk.
Prof. Daphne Kos, AP University College Antwerp and KU Leuven, spoke about occupational performance of people with MS and how to assist them. It is established that the life balance of people with MS deteriorates as the disease advances. There are several apps that have been developed to assist people with MS, e.g. apps: showing wheelchair accessible places; registering completed activities; for coaching; and to monitor occupation balance.
Prof. Joanna Zakrzewska gave an overview on trigeminal neuralgia (TN) in MS. It is thought that 2-4% of those with TN have MS. The characteristics of TN are distinctive and one should be mindful of patients using words such as “electric shock and lightening”. Patients with MS and TN have more bilateral pain, use a wider range of medications and undergo more ablative surgery. The progression of TN shifts overtime from periods of remission to constant exacerbation with many patients suffering depression. The evidence of medical management has been reviewed and AAN and EFNS guidelines recommend Carbamazepine as first line treatment; whilst new drugs are in development, e.g. small molecules to block sodium channels.
The closing plenary saw Sue Thomas (chief executive of NHS commissioning excellence) give an overview of the burden of hospitalisation in MS and highlighted an alarming lack of knowledge in the prevalence of MS within the regions of the UK. Care for patients with MS, especially unplanned care, is a huge burden on the NHS; for example in 2013/2014 non-elective admissions for these patients in England cost the NHS £43 million. Many of the admissions could be avoided thus reducing the cost to the NHS. This compliments the findings of the GEMSS project (www.mstrust.org.uk) (presented by Geraldine Myers). The report highlighted the positive impact MS specialist nurses (MSSNs) have on the wider society, not just improving the quality of life for MS patients but also benefitting the economy (reducing both ambulatory care costs and prevention of unplanned hospital admissions) and bringing value to their families and carers.
The conference was closed by Prof. Neil Scolding who spoke about the advances in cell therapy for MS. Prof. Scolding highlighted three avenues for cellular therapy in MS, 1 – oligodendrocyte replacement, 2 – restorative cell therapy and 3 – immune system replacement.
The oligodendrocyte cellular therapy does not appear to be a fruitful path as these cells are already present within the brain and spinal cord. The question remains; if they are there, are they working normally? Can the cells be encouraged to be more “effective”? It appears that oligodendrocyte replacement has become more pharmacological rather than treatment directed to the lesion, such as small molecules for myelin repair e.g. anti-lingo antibodies and repositioned drugs.
With regard to immune system replacement there is a controversial theory that axonal loss is due to an immune system dysfunction. The haematopoietic stem cell transplantation (HSCT) combines conditioning of the immune system (using chemotherapy agents) to remove the bone marrow and replace with an intravenous bone marrow graft (which can be autologous or matched donor). Results look promising with evidence suggesting 80%-85% reduction in relapses. However, there were no comparative controls. It is prudent to note the mortality rates of HSCT are 1.3%-5% and this therapy’s effect on progression is debated.
Restorative therapy utilises bone marrow (BM) derived stem cells, which have a role in normal health and repair. It is thought that these cells, in the presence of tissue damage, can attract more of these cells to repair tissue. They can reduce inflammation locally and release growth factors, regulating the local tissue stem cells. This is the idea of neurological immune reprogramming via these cells to effect demyelination and protect and reduce axonal and neuronal loss. The SIAMMS trial demonstrated injecting BM derived cells intravenously is safe with an improvement in visual evoked responses, however the efficacy remained unclear. This led to the ACTiMuS trial; a phase II blinded crossover study (currently ongoing). This field is expanding/changing and moving fast. From 18 clinical studies reported or known to be in progress there are now at least 47. Of note, the need for regulated clinical trials is very important.
Overall the meeting was highly interactive and educational. The talks were very interesting and highlighted the need to drive health efficiencies without reducing the quality of care provided. Re-purposing of drugs would not only be crucial to the care of MS patients in the UK, but there is the potential to impact patients in countries where DMTs are scarcely available. The idea of re-programming the neurological immune system is one that is evolving and definitely one to watch.
