About Martina Slapkova

Research Information Co-ordinator at the Motor Neurone Disease Association

Shining a light on our non-clinical fellow: Using blue light to control muscle movement

The MND Association is proud to support the brightest minds of MND research. Outside of general healthcare and biomedical project grants that are usually awarded to senior researchers, we also offer opportunities to young researchers – these take the form of PhD studentships and fellowships.

Fellowships are awarded to post-doctoral researchers who are able to support a research project as the leading investigator. Depending on their qualifications, the fellowship can either be clinical (for healthcare professionals) or non-clinical (for researchers with purely academic background). In the last round of non-clinical fellowship applications in October 2016, the MND Association awarded a senior fellowship to Dr Barney Bryson of University College London. In his upcoming project, due to start in August 2017, he will follow up on the findings he found together with his team, led by Prof Linda Greensmith.

Using light to move muscles

The idea behind Dr Bryson’s innovative project is that we can use a stimulator that emits light to create electrical signals in motor neurones (that form connections with affected muscles), rather than attempting to create long nerve connections between the muscles and the spinal cord.

We could think of this as creating a new electrical circuit from a power supply to an electric motor after lots of the wires have been damaged. Instead of reconstructing the long wires from the power supply to the motor, the researchers can directly plug in a new device that is capable of controlling the motor (or muscle in their case).

How can we use light to move muscles?

To control muscle movement by blue light, the researchers first had to create specially-modified stem cells from mice, from which specialized motor neurones could be generated. These motor neurones produce a specific neurotrophic factor and a gene that is sensitive to light, which enables them to survive longer after their implantation, and their activity to be controlled using pulses of light, respectively.

After these cells had been constructed, they were implanted into damaged sciatic nerves (one of the nerves controlling movements of the leg) in mice. Due to the survival-promoting neurotrophic factor, the implanted motor neurones were able to establish strong connections (innervation) with an atrophied muscle. Once innervated, an optical stimulator was then used to activate the transplanted motor neurons, creating electrical impulses that directly led to contraction of the connected muscles. They are now using a sophisticated implantable optical stimulator that was developed by Prof Ada Poon at Stanford University (Montgomery et al., 2015).

Optical stimulator implant (£1 coin for scale)

Optical stimulator implant (£1 coin for scale)

 How will this work be followed up now?

Much work still remains to be done before this approach could work effectively in human patients, which is a major focus of Dr Bryson’s fellowship project. Specifically, he will investigate how to best promote innervation of muscle fibres once the motor neurones are implanted. This will be done by closely observing the process of innervation in a laboratory dish and identifying the factors that promote best neurone-muscle connectivity. This part of the project is of great importance as strong connections are necessary for the muscles to receive an electrical instruction to contract.

How will this help people with MND?

While still at an early, pre-clinical stage, this project has a potentially immense impact for people with MND as it could re-establish electrical signals to the diaphragm, our main breathing muscle. When this muscle is affected, the person’s breathing ability deteriorates and an artificial way to support breathing has to be implemented (eg non-invasive ventilation). By implanting light-sensitive motor neurones to the phrenic nerve, which controls the diaphragm muscle, an optical stimulator emanating blue light could then directly control contractions of this muscle, greatly improving the person’s ability to breathe as a consequence. The hope is to also use this mechanism for peripheral muscles in order to improve person’s movement abilities.

Dr Barney Bryson

“This exciting project represents the next step in the continued development of an entirely novel strategy to overcome the progressive loss of ability to control specific muscles that occurs in MND.

“Although this future therapy is not aimed at preventing or slowing down the progressive loss of motor neurons that occurs in MND, it effectively circumvents the problem and could enable specific muscle functions and movements to be restored in an artificial manner in MND patients whose muscles have been paralysed, thus improving their quality of life.” Dr Barney Bryson

 

To find out more about MND Association-funded clinical fellowship projects, you can read about Dr James Bashford’s project investigating muscle fasciculations, or Dr Pietro Fratta’s project looking at understanding the role of RNA in MND.

Many thanks to Dr Bryson for his input and comments on this article.

To read more about the development of the optical stimulator that Dr Bryson uses, see the original research paper by Montgomery et al. (2015).

 

Life of an MND researcher – part 2: PhD edition

Each year, the MND Association dedicates the month of June to raising MND awareness. This year, we focus on the eyes – in most people with MND the only part of their body they can still move and the only way left for them to communicate. Alongside the Association-wide campaign, the Research Development team selected six most-enquired about topics, which we will address through six dedicated blogs.

In our previous article we introduced four MND researchers who gave us an insight what a typical day in the life of a researcher looks like and what carrying out a research study actually involves. In this continuation article, you will get the chance to look into the lives of four PhD students, who give us an overview of their projects and their usual daily duties. Continue reading

Collaborating to find treatment for MND

21 June – MND Awareness Day

Each year, the MND Association dedicates the month of June to raising MND awareness. This year, we focus on the eyes – in most people with MND the only part of their body they can still move and the only way left for them to communicate. Alongside the Association-wide campaign, the Research Development team selected six most-enquired about topics, which we will address through six dedicated blogs. 

It is at the heart of the Association to fight MND by funding and promoting research into understanding the disease so that we can defeat it. However, we would not be able to fight this battle on our own and the support of various people is crucial to defeat this MND monster.

Everyone working in the field of MND research has one aim – to find what causes this disease and find a treatment to cure it. We have already written about the long elaborate process behind developing and licensing new drugs but we have not yet talked about the people who are essential for this process to run successfully. Continue reading

Life of an MND researcher: part 1

Each year, the MND Association dedicates the month of June to raising MND awareness. This year, we focus on the eyes – in most people with MND the only part of their body they can still move and the only way left for them to communicate. Alongside the Association-wide campaign, the Research Development team selected six most-enquired about topics, which we will address through six dedicated blogs.

We all know that rigorous research is the key to finding a cure for MND. Scientists are working hard every day to find the causes of MND, developing new treatments that would help tackle the disease and also looking for new ways to improve the quality of life of people currently living with the disease. But what does it take to have research at heart of everything you do? What is the typical day in the life of a researcher and what does carrying out a research study actually involves?

We asked eight researchers to give us an idea of what their research is all about and what their typical day looks like. Read about four of them in the following blog and keep an eye out for ‘Part 2: PhD edition‘ in the next few days… Continue reading

The journey of a drug – what it takes to be approved

Each year, the MND Association dedicates the month of June to raising MND awareness. This year, we focus on the eyes – in most people with MND the only part of their body they can still move and the only way left for them to communicate. Alongside the Association-wide campaign, the Research Development team selected six most-enquired about topics, which we will address through six dedicated blogs.

So far, there is no cure for MND. In the past 22 years, we have only seen approval of two drugs that were either shown to prolong the life of MND patients by several months (riluzole in 1995 in the US) or to slow down symptom progression (edaravone in 2015 in Japan). It is only reasonable that you might wonder ‘what is taking so long?’ or ‘why are there not more drugs available?’.

It is very competitive in the world of medicinal drugs. From thousands of chemical compounds that are gradually eliminated as they go through different stages of drug development, only one makes it near the finish line. This line represents approval for marketing authorisation and there is no guarantee that this ‘top compound’ will actually make it to the end. So let’s have a closer look at the individual stages that a potential drug has to go through in order to be crowned the champion. Continue reading

ANXA11 – another gene closer to understanding ALS

A new research paper has been published today in the Science Translational Medicine journal, describing a new gene implicated in developing MND. What is this gene and why is it important for our fight against MND?

Although they are not the sole cause of MND, genes play a big role in someone’s probability of developing the disease. A number of such genes that make a person susceptible to developing MND have already been identified, with most of them causing the rarer, inherited form of the disease.

A new addition to a list of genes that are related to development of ALS, the most common form of MND, has been discovered by researchers from King’s College London. Dr Bradley Smith and colleagues screened genetic data of an unusually high number of people of European origin: 751 with inherited – familial – ALS (fALS) and 180 with non-inherited – sporadic – ALS (sALS). Detailed analysis of this data found that specific mutations in the ANXA11 gene are associated with around 1% of all fALS and 1.7% of all sALS cases. Continue reading

Exploring the interaction between TDP-43 and RNA

In light of the upcoming Biomedical Research Advisory Panel meeting happening on Friday 7 April that will discuss which new research projects the MND Association will fund, we are pleased to report on the progress of one of our already-funded researchers. In their three year project, funded by the MND Association, Prof Annalisa Pastore (King’s College London) and Prof Gian Tartaglia (University Pompeu Fabra, Barcelona) are investigating the process by which TDP-43 binds to RNA. Below is a summary of the progress they made during their first year.

Background to the project

Alumni Board Meeting 2008

Annalisa Pastore, King’s College London

One of the causes of amyotrophic lateral sclerosis (ALS), the most common type of motor neurone disease (MND), is related to faulty functioning of the TDP-43 protein, a component that is naturally present in all of our cells. In healthy cells, TDP-43 resides in the centre of a cell (the nucleus) where it attaches to RNA and supports correct gene expression – that is, it helps to extract information carried by a gene to form proteins, the main building blocks of our bodies.

Continue reading

What is the deal with magnetic fields?

A recently published paper exploring the connection between occupational risk factors and MND has sparked lots of interest, especially by the media. The study in question, led by Dr Roel Vermeulen from Utrecht University, The Netherlands, reviewed and studied five occupational exposures that had previously been suggested to be associated with developing MND (specifically, amyotrophic lateral sclerosis; ALS). These factors included exposure to electromagnetic fields, electrical shocks, solvents, metals and pesticides. While a few studies investigating these factors were already conducted in the past, their results are not consistent.

Despite the vast coverage of this topic in tabloids, we wanted to describe the research paper itself – to explain what exactly the researchers did, what they found and what it all means. Continue reading

New urine-based biomarker opens a gate to improved tracking of MND

Researchers from the Flinders University, Australia and University of Miami have discovered a new protein that can act as a biomarker to track disease progression in people with MND. A paper written under the leadership of Dr Shepheard and Dr Rogers was published today in the research journal ‘Neurology’.


What is p75 and what do we know so far

mndassociationgeneral3The biomarker is a protein called p75, which initially
supports the growth of neurones during embryonic development and its levels markedly decrease after birth. Throughout our lives, p75 only reappears in higher levels when the body detects injury of the nervous system, and shows its presence in urine.

The researchers have previously shown that, after birth, mice with a mutation in the SOD1 gene, known to cause MND, had high levels of p75 after about 40 days from the onset of MND. This also coincided with increased levels of p75 in motor neurones found in tissue of people with MND after death.

Continue reading

Families for the Treatment of Hereditary MND (FaTHoM)

Scientists from the University of Oxford have set up ‘Families for the Treatment of Hereditary MND’ (FaTHoM), an initiative to bring together the community of families affected by inherited forms of MND. Their first meeting will take place in Oxford on Tuesday 18th April.

Most people living with MND cannot identify a relative who has also had the condition. However, around 5% of people with MND will have a family history of the disease, which is known as inherited or familial MND. This happens when a single faulty gene is passed down from parents to their children across number of generations.

Continue reading