Background
MichaelODywer

Researchers at the National University of Ireland Galway have identified an enzyme that has a key role in the spread and survival of blood cancer cells. The discovery, which focussed on the cancer multiple myeloma, has just been published by the internationally acclaimed journal, Blood.

Multiple myeloma is a cancer of the blood which results from an overproduction of plasma cells, the white blood cells that produce antibodies. It leads to problems such as anaemia, bone damage, kidney failure and elevated calcium levels. There are about 240 new cases of multiple myeloma diagnosed each year in Ireland.

The research team was led by Health Research Board (HRB) Clinician Scientist, Professor Michael O’Dwyer and Professor Lokesh Joshi of the University’s Glycoscience Group, which is supported by Science Foundation Ireland. The group studies the complex sugars which cover all cells in the human body, and many of the proteins in the bloodstream. Dr Siobhan Glavey, a medical doctor funded by the HRB, also had a key role lead in the study and was lead author on the paper.

HRB Clinician Scientist, Michael O Dwyer, Professor of Haematology at the National University of Ireland Galway says; “While treatments for multiple myeloma have improved over the last decade, and most patients are living longer, there is no cure. Our research is crucial because it sheds new light on the biology of multiple myeloma which could lead to new strategies to overcome resistance to treatment.”

“Working in close cooperation with Dr Irene Ghobrial from the Dana Farber Cancer Institute at Harvard in the US and colleagues from the Institute of Cancer Research in the UK, we focused on alterations in a process called glycosylation, a process whereby proteins and lipids are modified by specific sugars, because of its role in cell-cell interactions and the spread of cancer cells in the blood.”

“In essence, we have linked the overproduction of a specific enzyme called sialyltransferase to disease progression and worse outcomes in multiple myeloma. The increase in this enzyme activity causes a series of knock on effects; increasing glycosylation, which in turn increases the interaction of the cancer cells with receptors on the walls of blood vessels called selectins which then encourages their circulation, spread and retention in the bone marrow.”

“Our aim now is to prevent these interactions that cause the spread using specific enzyme and selectin inhibitors”.

Dr Graham Love, CEO of the HRB, commented on the importance of the research: “Understanding what causes multiple myeloma to progress, or generate worse outcomes, is the first step towards improving treatment. This discovery reinforces the transformational role our Clinician Scientists have in bringing real clinical questions to a research environment and delivering results back to the bedside.”

Neural Stem Cells
Stem cells can be manufactured for human use for the first time in Ireland, following Irish Medicines Board licensing of a new facility in Galway.

NUI Galway’s Centre for Cell Manufacturing Ireland aims to culture adult stem cells to tackle conditions such as arthritis, heart disease, diabetes and associated conditions.

The centre, which is one of less than half a dozen in Europe authorised for stem cell manufacture, has been developed by researchers at NUIG’s regenerative medicine institute.

Stem cells serve as the body’s repair mechanism. They can be isolated from tissues such as bone marrow and fat, and cultured in laboratory settings.

More controversially, embryonic stem cells have been highly valued for their ability to turn into any type of cell in the body, but scientists can now use reprogrammed adult skin cells to create a stem cell that is very similar to embryonic versions.

The centre will be opened today by Minister of State for Research and Innovation Seán Sherlock, at a time when the Health Research Board and Science Foundation Ireland have approved funding there for clinical trials on using mesenchymal stem cells – cells that can differentiate into a variety of types – for treatment of critical limb ischemia, a condition associated with diabetes that can result in amputation.

The new centre’s director Prof Tim O’Brien explained that the stem cells must be grown in the laboratory to generate sufficient quantities, following their isolation from the bone marrow of adult donors, and the facility will help Ireland to develop therapies for a broad range of clinical problems which do not have effective treatments today.

“It will also allow us to translate discoveries from the basic stem cell research programme led by Prof Frank Barry at the Science Foundation Ireland-funded REMEDI to the clinic, and to be competitive for grant funding under the Horizon 2020 programme of the EU,” he said.

Stem cell research in Ireland is in what scientists have described as a “legislative lacuna”, but this relates to use of embryonic stem cells and does not in any way inhibit the use of adult stem cells, Prof O’Brien explained.

“We can only engage in clinical trials with clinical authorisation from the IMB and approval from the hospital ethics committee, and we are currently seeking such approval for clinical trials,”he said.

“The license to manufacture is an essential pre requisite to seek permission to undertake clinical trials. The license certificate must be included with the clinical trial authorisation application.”

NUIG president Dr Jim Browne said the centre develops Galway’s role as a “med tech hub of global standing”, while Irish Medical Devices Association board member John O’Dea has pointed to the lucrative revenue to be earned from regenerative medicine products, valued at about €1.3 billion in 2013 and with a 40 per cent sales growth last year.

Some 70 per cent of pharmaceutical companies are working on regenerative medicine therapies – an area described as a crossover between biology and engineering – and NUIG estimates that there are over 1,900 cell therapy clinical trials under way globally.

(Report taken from the Irish Times)