A view from the President

After we posted yesterday’s blog (Thursday 10 October) about Giovanna Mallucci’s research in Leicester, we received a report on the story from the President of the MND Association, Prof Colin Blakemore.

The researchers identified a key pathway that might be a turning point in the search for effective treatments for many types of neurodegenerative disease and we couldn’t resist posting Prof Blakemore’s views:

The team at the MRC Toxicology Unit in Leicester has been studying mice with a so-called prion disease (very similar to Mad Cow Disease), produced by genetic modification of the mice or by infection. Prion disorders are known to be caused by unusual “misfolded” protein molecules accumulating inside nerve cells, and last year Professor Mallucci discovered why the nerve cells die. When unusual protein molecules build up inside a nerve cell, the cell shuts down the production of its own proteins in self-defence. But if the shut-down continues for too long, the nerve cell starves itself of its own proteins and dies.

One of the most puzzling aspects of other neurodegenerative disorders is that the many different sorts of disease (Alzheimer’s, Parkinson’s etc) affect specific types of nerve cells in particular parts of the brain. But there is good evidence that unwanted proteins of one sort or another accumulate inside nerve cells in most if not all of these neurodegenerative diseases. At the heart of Professor Malluci’s work is that hope that a drug that prevents the shutting-down process might be able to protect nerve cells in a wide variety of diseases, possibly including Motor Neurone Disease, PSP and CBD, as well as Alzheimer’s and Parkinson’s.

In her new report, published in the important journal Science Translational Medicine, Professor Mallucci describes success in halting the death of nerve cells in mice with prion disease, using drug therapy.  One the most important features of this work is that the drug (an experimental drug produced by GSK) is given by mouth and can cross from the blood into the brain – a crucial requirement for any drug intended for general use.

While this research is extremely exciting, it is important to be realistic about the hurdles that have to be overcome, and the time that it is likely to take, before a treatment for human disease might be available.

For one thing, it is not yet certain that the same type of drug will be effective in preventing nerve cell death in other sorts of neurodegenerative disease. But that question can surely be tackled in other mouse models of disease and perhaps in cultures of human nerve cells produced in the test tube from skin cells donated by patients (an approach that is being widely used to study the degenerative process and to test the effectiveness of potential new drugs).

Unfortunately, the particular GSK drug used in Professor Mallucci’s research is quite toxic. As she said “We’re still a long way from a usable drug for humans – this compound had serious side effects.” It caused dramatic weight loss, as well as diabetes, due to effects on the pancreas.  But with modern methods for drug design and testing, there is real hope that other effective drugs with fewer side effects will be found.

Even if less toxic drugs are soon discovered, it will take many years for the clinical trials needed to establish the effectiveness and safety in human patients. Medical charities are ready to play a very important role in that stage of the research, because their members include many patients who have already offered to take part in such clinical trials.

Colin Blakemore
President of the MND Association
Emeritus Professor of Neuroscience, University of Oxford
Former Chief Executive of the Medical Research Council