"Untold possibilities"

Last time I wrote about Bram Harrison, the DJ with Locked-in Syndrome. A bit of the I article I omitted was this: "Harrison is cognitively sharp, funny and mischievous; a technology geek who holds faith in medical progress, stem cell advances in particular, to perhaps unlock him one day." 
Browsing the MND Association website this afternoon I came across this article: Association-funded stem cell research achieves milestone. I remember talking to Tom Isaacs, with Parkinson's, who walked 4500 miles round the British coast raising funds for research into that disease, about ten years ago. He had great faith that research would see a cure even within his lifetime. He founded The Cure Parkinson's Trust, whose watchword is "Hope". Neither he nor I could have foreseen the exponential acceleration of research into neurological conditions over that time. What particularly excites me about the research described below is that it doesn't use embryonic stem cells (i.e. obtained from fertility-treatment excess embryos) but induced pluripotent stem cells (iPS cells) obtained from adult skin cells. For me it poses less of an ethical problem. Predictably this news didn't hit the national headlines, in contrast to embryonic stem cells - which seems to with strange regularity.


However, this is a really good news story for the reasons the article explains.

A cutting-edge stem cell research programme funded by the MND Association has produced a key development that could have a powerful impact on the search for treatments for MND.

The international research team, led by world-class scientists from the University of Edinburgh, King’s College London and Columbia University (New York), has for the first time used stem cells derived from adult skin to generate living human motor neurones that display key characteristics of MND.

These diseased neurones offer huge potential. As a uniquely realistic laboratory model of the disease they could allow for rapid screening of thousands of drugs, as well as furthering understanding of underlying disease mechanisms.

What did the researchers do?

Researchers started with skin cells donated by a 56 year old man with the rare, inherited form of MND caused by mistakes in the TDP-43 gene. Although abnormalities in this gene are uncommon, the protein produced by the TDP-43 gene has been implicated as a pivotal player in the majority of cases of MND.

Scientists used a special cocktail of chemicals to ‘reprogramme’ the donated skin cells, turning them first into stem cells similar to those derived from embryos and then into motor neurones.

Compared to motor neurones generated from the skin cells of healthy individuals, the neurones with the abnormal TDP-43 demonstrated decreased survival and increased vulnerability to damage.

The TDP-43 protein also displayed a greater tendency towards clumping together, or aggregating. This is a recognised hallmark of diseased neurones in MND and for the first time provides scientists with the opportunity to see the direct effect of abnormal TDP-43 on living human cells.

“Untold possibilities”

The team’s results, published as a ‘free to access’ article in the journal PNAS, provide proof of principle that skin cells can be successfully turned into diseased motor neurones.

At the same time they represent significant progress towards the key aim of this groundbreaking £800,000 programme: to develop and characterise a robust human cell model of MND that can be made available to scientists across the world.

Dr Brian Dickie, director of research development at the MND Association, said: “This advance is a significant milestone on the road to developing a laboratory model of MND that faithfully reflects the cellular events happening in the patient. It is also a testament to the importance of international collaboration, with eminent scientists from leading institutions around the world focused on the common goal of understanding and, ultimately, defeating this devastating disease”.

Prof Siddharthan Chandran of the University of Edinburgh, who is leading the programme, said: “Using patient stem cells to model MND in a dish offers untold possibilities for how we study the cause of this terrible disease as well as accelerating drug discovery by providing a cost effective way to test many thousands of potential treatments.”

How much better is it to cherish hope than to abandon it. Wasn't it Dante's Hell that had the sign over it, "Abandon Hope, all ye who enter here"? Well, here's a reason for hope, maybe not for my generation, or just maybe so....