This blog is part of the ‘Highlights from Perth’ collection of articles, where you can read about the content of some of the talks and posters presented at the 30th International Symposium on ALS/MND. All presentations have a code beginning with ‘C’ followed by a number (e.g. C50). This will help you locate the specific abstract mentioned throughout the post in the official abstract book.
Researchers are invited to present their work as either a platform (oral) presentation or as a poster. Session 2B of the Symposium’s platform presentations looked at clinical trials. Here we summarise the session with four talks reporting concepts, updates and results of the trials being investigated. This includes the Healey ALS Platform Trial, Ibudilast, NurOwn, and Tofersen.
‘From antibiotics and insulin to blood transfusions and treatments for cancer or HIV, virtually every medical achievement in the past century has depended directly or indirectly on research using animals’ – from the Royal Society’s position statement on the use of animals in research.
We know that talking about using animals in research is an emotive topic. We appreciate that some people will never accept that using animals in research is necessary, and we understand that it is not our place to try and influence anyone’s opinion on the use of animals in research. The purpose of this blog is to explore how using animal models of MND can further our understanding of this devastating disease, and how animals make it possible for potential new treatments for the disease to move forward into clinical trials in people.Read More »
After its successful premiere in 2017, the University of Oxford organised another meeting of people affected by inherited MND, called ‘Families for the Treatment of Hereditary MND (FaTHoM)’. This turned out to be yet another excellent day where MND clinicians-researchers presented on topics such as genetics of MND, genetic testing and gene therapies. Below you can find out more about what was presented on the day and links to the videos of recorded talks.
Understanding familial MND
Introducing the rationale of the meeting, Prof Martin Turner set the scene by explaining the great difficulty in understanding the disease due to its many possible causes. Being such long cells, many things can go wrong in the motor neurones and in the vast amount of their support cells (such as astrocytes or microglia). But one factor can help us understand the disease better – genes.
A recent press release by the pharmaceutical company Biogen reported preliminary results from an ongoing clinical trial investigating a form of precision therapy in people with SOD1-related MND. This drug, known as tofersen, is now in the final stages of Phase 1/2 testing in centres across the world, including Sheffield in the UK.
Tofersen is an antisense oligonucleotide (ASO), designed to prevent the faulty disease-causing protein from being made. Proteins, the building blocks of the body, are created from our genetic information (DNA) via its photocopy (RNA). If a piece of DNA is damaged, the RNA will also be damaged, leading to formation of a faulty protein and creating issues in the body. Tofersen is a synthetically-created RNA directed to stick to the faulty photocopy (RNA) preventing it from making faulty proteins.Read More »
The research team frequently gets asked about the effectiveness of alternative therapies and their use as treatments for MND. Here we report on a recent paper that looked at the effects of ashwagandha, or Indian ginseng, in a SOD1 mouse model of MND.
For around 3000 years Withania somnifera (WS), commonly known as ashwagandha or Indian ginseng, has been used in Ayurvedic and indigenous medicine around the world, and is thought to have powerful rejuvenating and life-prolonging qualities. But there is increasing evidence which suggests that the plant extracts (root, leaf or fruit) also have neuroprotective properties, and this has been demonstrated in several models of neurodegenerative diseases including MND.Read More »
Love them or loath them, the band Steps’ first single ‘5,6,7,8’ was a techno line dance song released in 1998 from their debut album ‘step one’, with the B side ‘words of wisdom’.
Using this forced and purely tenuous link and an equally awkward segue, I would like to share with you the news that the journal Neurology this week published further words of wisdom from Professor Adriano Chio, Professor Ammar Al-Chalabi and colleagues, that revisits the multistep hypothesis of MND. Their previous work showed that when no genetic cause is considered, developing MND is a six-step process. In their most recent work, the team investigated how many of the steps does a genetic mutation account for in this multistep process, with a focus on the most common MND causative genes SOD1, TARDBP, and C9ORF72.Read More »
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
The 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.
With all the talk of new gene discoveries in recent years, the Sunday morning scientific session returned to the original discovery in 1993 that mutations in the SOD1 gene were responsible for around a fifth of familial (inherited) MND cases and 2-3% of all cases of the disease.
Although much of our understanding of MND in the past two decades comes from SOD1 laboratory models of the disease, we still don’t know exactly how SOD1 kills motor neurons. But that hasn’t stopped several groups from working on a number of innovative ways of protecting motor neurons from SOD1 toxicity. Although focused on a relatively rare form of MND, some of the strategies being followed could potentially also be applicable to other forms of the disease.
A number of articles were published in various news sources on 11 July 2014, highlighting how scientists in Sheffield are working towards testing a promising treatment for a rare inherited form of MND caused by the SOD1 gene. Here we write about the research and what it means for people living with MND.
The Sheffield Institute for Translational Neuroscience (SITraN) specialises in research into MND and other neurodegenerative diseases. Recently the institute received an anonymous donation of £2.2 million to help translate their research from the lab to the clinic. This is a huge amount of money into MND research and this donation will enable the researchers to further our understanding of the disease.
We know that approximately 10% of cases of MND are inherited. This means that they are characterised by a strong family history and the disease is caused directly by a mistake in a specific gene. Of these 10% of cases, 2% are caused by the SOD1 gene (meaning that for every 100 cases of MND, 10 cases are inherited and of these, only 2 are directly caused by the faulty SOD1 gene).
Prof Mimoun Azzouz’s research at SITraN was reported in a number of news outlets, highlighting how his research is paving the way to a treatment for a rare form of MND. His research is at a relatively early stage, where he has only just begun investigating the use of a technique known as ‘gene therapy’ in mice affected by the SOD1 inherited form of MND. If the research goes to plan, he will be able to submit a proposal for regulatory approval by August 2015.Read More »
The 24th International Symposium on ALS/MND began in Milan today with a record number of over 950 delegates attending to hear the latest news in MND research.
Inherited MND is a rare form of MND characterised by a family history of the disease. Over recent years more and more genes have been discovered, which has lead to an increase in individuals wishing to pursue genetic testing.
A genetic test consists of a sample, which is then sent off to a genetic laboratory. Here the blood sample is then screened for the MND-causing genes.
The gene that is faulty in inherited MND can differ between one affected family and another. Mistakes in genes called SOD1, TARD-BP, FUS and C9ORF72 between them account for about 65 – 70% of cases of inherited MND. Scientists have yet to identify the gene defects that cause the remaining 30%.