Picture of face and eye

Do the eyes have it? Could Resistant Nerves See Our Way to a Treatment?

The Science Show on ABC Radio National in Australia, features an interview with Professor Justin Yerbury on Saturday 17th August.

The article containing the interview titled ‘Resistant nerves could lead to treatment for neurodegenerative disease‘ is a fascinating insight into Prof Yerbury’s work on the  delicate balance of proteins in solution within our nerves and how this is interrupted in MND.

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Developing a drug screen using nerve cells from a mouse model of MND

In a previous research project funded by the MND Association, Prof Kevin Talbot and colleagues from the University of Oxford developed a new TDP-43 mouse model of MND. Compared to other mouse models of MND, this one accurately reflects the symptoms of the disease and levels of the TDP-43 protein as seen in humans.

TDP43 location in the cell
Location of TDP-43 protein (shown in red) in healthy nerve cells, and how it moves into different parts of the cell in MND

This model of MND also shows how the TDP-43 protein becomes displaced from the nucleus (command centre of the cell) out into the cell cytoplasm, which makes up the cell body. Once TDP-43 has moved to the cytoplasm it is very difficult to shift, as it forms protein aggregates or clumps. It is thought that these clumps contribute to motor neurone cell death.

Prof Talbot’s latest project, together with researcher Dr David Gordon, is using cultured nerve cells from this new mouse model to screen a large library of drugs (our project reference: 831-791).

In the next two years, they will create an automated computerised imaging system that can detect the TDP-43 protein within the nerve cells (and see if it has moved out of the nucleus). With this imaging software the researchers aim to screen thousands of drug compounds in a short space of time, including some which have been approved for other illnesses. A ‘good’ drug will make TDP-43 stay in the correct location within the nerve cell’s nucleus.Read More »

When is Lou Gehrig’s Disease not Lou Gehrig’s Disease?

A few months ago, I attended a media training day.  It involved a series of ‘mock’ interviews on radio and TV, performed in studios by experienced journalists. For the first couple of attempts, I was truly awful – it’s so easy to get tied in knots by reporters, especially if they are looking for a particular ‘newsworthy’ angle. 

 So, when I saw the story in the New York Times (picked up in the UK by the Guardian and Telegraph) suggesting that the famous baseball player Lou Gehrig might not have had Lou Gehrig’s disease (so whose disease did he have then?) I had a pang of sympathy for the researchers who were interviewed for the article.  I suspect when they found the article in the Sports section rather than the Science section, they realized the story might have turned out slightly different than they originally intended …..

 For the record, the story broke after a research team in Massachusetts published a research paper in a Neurology journal. The title of the paper is: ‘TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy’.  Not a mention of Lou Gehrig or baseball….

 The researchers had looked at post mortem brain and spinal cord tissue from 12 cases of chronic traumatic encephalography (CTE) which, as the name suggests, has long been associated with impact sports such as Boxing and American Football. Within those 12 cases, (all of whom were professional sportsmen: American Footballers, Boxers and Ice Hockey players…but still no mention of Lou Gehrig or baseball…) there were three cases where CTE and MND had been diagnosed in the same individual.

 They examined the protein aggregates (which can be thought of as classic cellular ‘hallmarks’ or ‘signatures’ of neurodegenerative diseases). They looked at CNS tissues from the CTE cases and compared them with those of the three CTE + MND cases. And found a very similar protein ‘hallmark’ in all cases, However, when they then compared this  with tissue from people with sporadic MND, who had no background in professional sports, they found that there were some key differences in the protein ‘hallmark’.

They therefore suggest that repetitive head trauma may not only be an underlying factor for CTE, but also could sometimes be a predisposing factor for MND and this is accompanied by a distinct protein hallmark. This is supported by some, albeit weak, epidemiological studies in MND, linking mechanical/head trauma with a slightly increased incidence of MND later in life.

Scientifically, this is a very interesting finding, but the fact that the protein hallmark is different is not the same as saying that the disease is not MND, as the New York Times suggests.  At this point I should point out that the newspaper actually talks about Amyotrophic Lateral Sclerosis (ALS:  the most common form of MND) as it is important to fully understanding the story.

 In their research paper, the scientists are very careful to use the term ‘motor neuron disease’ as much as possible. This is highly unusual for USA-based researchers, who virtually always talk about ALS instead of the more general ‘umbrella’ term of MND, favoured by us in the UK. They did this because they wanted to emphasize the point that MND is not a single disease. There are many ‘sub-types’ that come under the MND umbrella – some can be characterized by clinical signs, others can be clinically the same, but may be classified by close examination of the pathological hallmarks. All they are saying in their paper is that when there is a history of repeated head trauma associated with MND cases, there may a distinct pathological hallmark that occurs, but the disease is still very much MND.

Getting back to the ALS ‘subtype’ of MND, we know that the protein hallmarks can be different for different ALS cases. For example, the protein pattern is different for sporadic versus familial forms – and indeed between familial forms with different known genetic causes, such as the SOD1, FUS and TDP-43 gene mutations. They are all still forms of ALS.

Researchers openly acknowledge that ALS itself needs to be classified into distinct subtypes and that this is an ongoing process.  At the MND Association’s International Symposium, in 2007, the Opening Presentation by Prof Mike Strong was titled ‘ALS: one disease or many?’.  The research community knows that the answer is ‘many’.  The journalists at The New York Times – at least in the Sports Department – apparently do not.

 So, did Lou Gehrig have ALS or not? We can’t say for certain, as he was cremated, so the definitive examination of post-mortem tissue can’t be performed.  But, based on the clinical evidence, what we can say is that even if multiple head trauma from contact with fast-moving baseballs was a contributing factor, it was a contributing factor to a form of ALS – aka Lou Gehrig’s Disease!