Here you can find the latest MND research news from around the world. Stay tuned to find out about clinical trial outcomes, breakthroughs in the lab, interesting research papers and more.
Tofersen receives positive opinion from European Medicines Agency Committee
23 February 2024
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has announced a positive opinion for the approval of tofersen (Qalsody) for the treatment of SOD1 MND. The recommendation is for a marketing authorisation under exceptional circumstances, which means tofersen will be subject to monitoring once approved. The CHMP panel reviews the scientific evidence and forms an opinion on whether new drugs should be approved in Europe. The committee based their review on data from the phase 3 VALOR trial and its open label extension. This positive recommendation will now be sent to the European Commission who will make the final decision on approval in the EU within 67 days. You can read more about this recommendation here or in a press release.
The EMA determines approvals for the EU. It is thought that Biogen are currently pursuing the International Recognition Procedure (IRP) for approval in Great Britain (England, Wales and Scotland). This procedure allows the regulator for Great Britain, known as the Medicines Healthcare products Regulatory Agency (MHRA), to take into account the decisions from trusted regulatory partners, such as the EMA, when making the decision to approve new treatments.
Regulatory approval in Great Britain does not automatically mean the treatment will be available on the NHS. First, it must be assessed by NICE, who advise the NHS whether a new treatment is cost effective. During their evaluation NICE review evidence from clinical trials, assess the benefits and quality of life the treatment would provide and weigh these against the cost of the treatment. Tofersen is in the early stages of this process with NICE.
A phase 3 trial of tofersen, called ATLAS, is currently underway. This trial is investigating whether treatment before physical symptoms appear can delay the onset of symptoms and slow disease progression when symptoms do develop. You can find out more about tofersen and ATLAS on our website.
SAR443820 clinical trial does not meet primary endpoint
20 February 2024
Denali Therapeutics reported that the phase 2 clinical trial of SAR443820 (HIMALAYA) did not meet its primary endpoint. This suggests that there was no significant change in ALSFRS-R (from baseline to 24-weeks) for those who received the treatment compared to those who received the placebo (dummy drug). Further details on the trial outcome are expected in the coming months. You can read more about SAR443820 here.
Single-dose gene therapy stops MND progression in early laboratory research
15 February 2024
Researchers from Macquarie University have developed a single-dose gene therapy which has been found to clear clumps of a toxic protein, called TDP-43, in early laboratory testing. Toxic clumps of TDP-43 are found in 97% of cases of MND. The researchers found that when TDP-43 is faulty, levels of another protein, called 14-3-3θ, are increased. These two proteins then interact, and this leads to build up in cells. The new potential gene therapy (CTx1000) can help to control the interaction between the two proteins.
In early laboratory testing, in models of MND, a single dose of CTx1000 only targeted faulty TDP-43. This meant that the healthy version of TDP-43 could still be produced and work as it should, while the faulty version was prevented from forming. The researchers now hope to continue the development of CTx1000 which will hopefully lead to testing in clinical trials. You can read more about CTx1000 here.
MND Association announces new £5 million investment to give more people with MND access to clinical trials
6 February 2024
The MND Association are developing a new network of MND Association Research Nurses across England, Wales and Northern Ireland. The new Network aims to give everyone diagnosed with MND a chance to take part in research. The specialist nurses will help people with MND navigate the research trial process – providing information, identifying trials and research opportunities patients are eligible for, explaining what’s involved, and supporting their ongoing involvement. MND Association Research Nurses will work alongside multidisciplinary teams in Care Centres and Networks, with the first nurses expected to be in post by the end of the year. Find out more in a news story.
Function of the cell's powerhouse linked to MND severity
29 January 2024
Researchers from Sheffield Institute for Translational Neuroscience (SITraN) have discovered that the function of the powerhouse of the cell (mitochondria) can affect how long people with MND live. Mitochondria are essential for cell survival and previous research has suggested that the mitochondria may not produce enough energy in people with MND.
The researchers found that the function of the mitochondria does not affect the risk of developing MND. However, there was a link between function of the mitochondria and survival. This suggests that new therapies could be developed to change the function of the mitochondria and potentially slow disease progression and increase survival time. You can read more here.
AB Science provide update on European approval process for Masitinib
26 January 2024
AB Science have provided an update on the ongoing marketing authorisation application of masitinib for the treatment of MND by the European Medicines Agency (EMA). The Committee for Medicinal Products for Human Use (CHMP), part of the EMA, have asked AB Science to submit a written response to the List of Outstanding Issues. This has pushed back the timeline to a decision. A decision whether to approve masitinib is now expected before mid-2024.
Masitinib is a potential treatment for MND which is currently being tested in a phase 3 clinical trial in the US and Europe. A previous phase 2/3 trial showed potentially promising results for a specific group of people with MND. You can read more about Masitinib here.
New research investigates family members risk of MND
22 January 2024
A new research study has suggested that family members of someone with C9orf72 MND may have an increased risk of developing MND, regardless of whether they carry the gene change or not. Researchers looked at 131 families from Ireland who had been affected by C9orf72 MND, the most common genetic form of MND. They found that some family members were also diagnosed with MND but did not have the C9orf72 gene change. This suggests that family members may have a higher risk of developing MND, even if they do not have the gene change. The researchers emphasised that each family is different and that this research highlights the importance of individualised support. Further research is now needed to understand more about why this increased risk may occur and if this is observed in other populations.
Top-line results from trial testing oral edaravone suggests no benefit
10 January 2024
Ferrer have announced the top-line results from the Phase III ADORE clinical trial testing oral edaravone (FNP122) in people with MND. The trial did not meet primary or secondary endpoints. There was no significant different in change in ALSFRS-R (from baseline to 48-weeks) for those who received the treatment compared to those who received placebo (dummy drug). This suggests that oral edaravone is not beneficial for people with MND. The data also showed no improvement in long-term survival when comparing oral edaravone to placebo over 72-weeks. This formulation of oral edaravone (FNP122) was found to be safe and well-tolerated. You can find out more about the results here or read more about the ADORE trial here.
Ferrer have also announced that the open-label extension of the ADORE study, where everyone on the trial has an option to receive the treatment, will now end due to the lack of benefit observed.
Further results from the CNM-Au8 trial announced
22 December 2023
Clene Nanoscience has reported additional data from the HEALEY ALS Platform trial. The additional data is from ‘post-hoc’ analysis of the trial, which means the analysis was completed after the trial was concluded and was not the primary objective of the trial.
Neurofilament light chain is a marker of nerve damage and levels are high in people with MND. Reducing the levels suggest a reduction in disease activity and less damage is happening to motor neurons. During the 24-week randomised portion of the trial, those who received CNM-Au8 had a 10% reduction in neurofilament compared to those who received the placebo. After 24-weeks everyone on the trial was now able to receive the treatment. A 16% decrease in neurofilament from baseline to 76-weeks for those who received CNM-Au8 compared to those who initially received placebo. Read more in the press release.
Clene also announced that they had approached the US Food and Drug Administration (FDA) to discuss accelerated approval for CNM-Au8. It has been reported that the FDA have rejected this request, stating that the results offered insufficient evidence of the reduction of neurofilament light chain.
A new precision-medicine gene therapy was shared at the 34th International Symposium on ALS/MND
9 December 2023
Researchers from University College London and The Francis Crick Institute have developed a brand-new type of gene therapy that could be used to treat ALS, FTD and other neurodegenerative diseases. This new technique uses biology that is known to go wrong in neurons in MND and exploits it to increase the levels of proteins that are usually decreased in diseased motor neurons.
TDP-43 is a protein which becomes faulty in ALS and FTD and it’s function of regulating protein instructions is lost. This means that the instructions can contain pieces of information that are not needed to produce the protein (cryptic exons). This new gene therapy relies on these cryptic exons being included. The therapy contains a gene that is engineered to have a cryptic exon which, when included in the protein instructions, kickstarts the cell to make a specific protein (such as UNC13a or Stathmin-2) which is usually reduced in the disease.
This precision medicine approach means that the gene therapy only acts in cells that are affected by the disease and only when TDP-43 becomes faulty. The gene therapy could help to reduce the toxic effects of faulty TDP-43 in neurons and restore protein levels in ALS/FTD.
Top-line results announced from phase 2b trial of potential treatment called Prime C
6 December 2023
NeuroSense have announced the top-line results from the Phase 2b trial of Prime C. This Phase 2b trial included 69 people with ALS, from Canada, Italy and Israel, who were randomised to get either Prime C or a dummy drug (placebo) for six months. The initial results from this trial have shown that the potential treatment is safe and well tolerated by people with ALS. Prime C was also found to slow disease progression by 29% on the ALSFRS-R and slow decline in lung function by 13% for those on prime C compared to placebo.
While this was a small trial, the initial results are very promising and support the need for a bigger phase 3 trial, which is already being planned. Further results from this trial will be announced in early 2024 which will tell us more about how the treatment is working within the body. You can read more in a press release.
BrainStorm Cell Therapeutics have announced a meeting to discuss another clinical trial of NurOwn
20 November 2023
BrainStorm Cell Therapeutics have revealed that they will be meeting with the Food and Drug Administration (FDA) on the 6th December to discuss the path forward for NurOwn. After the FDA advisory committee voted against the approval of NurOwn in September, the application to the FDA was withdrawn and another phase 3 trial was recommended to test the potential therapy. BrainStorm Cell Therapeutics and the FDA will discuss the design of this trial so that it meets the FDA requirements for re-submitting the application if the results are positive. You can read more in a press release or find out more about NurOwn here.
New gene therapy targeting TDP-43 shows promise in animal models of MND
9 November 2023
A new gene therapy, being developed by a company called Sola Biosciences, has been found to extend survival and improve motor function in mice with MND. SOL-257, the potential gene therapy, aims to target a protein called TDP-43 which becomes faulty in around 97% of people with MND. The possible new therapy is designed to help restore the structure of TDP-43 and kick start the breakdown of the faulty protein, which might help to slow the progression of the disease and may reduce motor neuron death.
SOL-257 was tested in two different mouse models of MND. Treatment was given in the very early stages of MND in one mouse model and three months after the onset of disease in the other model. In the early treatment group, the gene therapy was shown to extend survival of the mice to 17 weeks compared to 8 weeks without treatment. In the later stages of disease, the treatment was found to reduce the number of toxic clumps of TDP-43 and improve motor function and muscle strength of the mice compared to those who did not receive the gene therapy. These findings support the continued development of the potential therapy for MND. You can read more about it here.
Virtual MND Research Institute officially launches
3 November 2023
The new UK Motor Neuron Disease Research Institute (UK MND RI) officially launched in London on 3 November 2023. The Institute aims to accelerate the search for effective treatments, and ultimately, a cure for MND. The virtual Institute brings together a network of MND labs, clinical centres and researchers carrying out world leading MND research across the UK. It is co-directed by MND clinician researchers Professor Ammar Al-Chalabi at King’s College London and Professor Chris McDermott at the University of Sheffield.
The Institute will enable clinicians, researchers and people with MND, together with charities, including the MND Association and other funders, to work together in a more coordinated way, to speed up drug discovery and drug development. Scientific discoveries will be translated into knowledge that drives new approaches to treatment, and then test those potential treatments in clinical trials. Find out more in a news story or follow the UK MND RI on social media to keep up to date with the latest information and news.
New research assesses the risk of developing MND for people with the C9orf72 gene mutation
20 October 2023
Researchers from University Medical Centre Utrecht have assessed the risk of developing MND for people who carry a gene change in the C9orf72 gene. Previous studies had estimated that the risk of developing MND for these people was between 90 and 100%. The researchers looked at first degree relatives (parents, siblings and children) of those with C9 MND in the Netherlands and collected data on them using surveys. They found that the mean risk of developing MND at age 80 for first-degree relatives who carry the C9orf72 mutation was around 24%, much lower than previously reported. However, they also discovered that risk was different for different families and could be anywhere between 16% and 60%. This means that, while the risk may be lower than previously thought, individualised testing would be needed for each family to accurately predict the risk for each family. You can read the publication here.
BrainStorm announce they are withdrawing the Biologics License Application for NurOwn
18 October 2023
BrainStorm have announced that they are withdrawing the Biologics License Application (BLA) for NurOwn in the United States. This is following the Food and Drug Administration (FDA) Advisory Committee meeting which discussed the approval of NurOwn for the treatment of ALS. Overall the Committee voted against the approval of NurOwn. BrainStorm have also announced that they will be requesting a meeting with the FDA to discuss the path forward for NurOwn, as well as looking at the next steps, including the development of protocol for an additional clinical trial. You can read more in a press release or find out more about NurOwn here.
AMX0035 receives confirmation of negative opinion from European Medicines Agency Committee upon re-examination
13 October 2023
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) have confirmed their initial negative opinion for the conditional approval of AMX0035 (Albrioza). This is the result of a re-examination of the application following a negative opinion that was announced in June. The CHMP panel reviews the scientific evidence and forms an opinion on whether new drugs should be approved in Europe. The committee based their review on data from the phase 2 CENTAUR trial. You can read more in a press release.
The EMA determines approvals for the EU. Since Brexit, a process (known as the European Commission Decision Reliance Procedure) has been put into place so that the regulator for Great Britain (England, Wales and Scotland), known as the Medicines Healthcare products Regulatory Agency (MHRA) may rely on a decision taken by the EMA on the approval of new treatments.
A phase 3 confirmatory trial of AMX0035, called PHOENIX, is currently underway. Topline results are expected mid-2024 and, if successful, may help to support a re-application to the EMA. You can find out more about AMX0035 and PHOENIX on our website.
Additional data announced for the CENTAUR trial of AMX0035
10 October 2023
Amylyx, the company behind AMX0035 have announced the publication of additional data from the Phase 2/3 trial CENTAUR. This additional data comes from a new analysis which compared the long-term survival data (data from the trial and the open label extension) of those on AMX0035 with a historical control group. The historical control group was made up of data from the PROACT database which includes records of participants who have previously taken part in other clinical trials. Using this historical control group rather than the placebo group in the trial (who then went onto receive the drug on open label extension) removes any bias that could come from switching to receiving the active treatment.
The new analysis found that the median overall survival was 10.4 months longer in the group who were taking AMX0035 than in the PROACT control group. The findings also suggested that those taking the drug had a 52% lower risk of death over the duration of follow-up when compared to the historical control group. You can read more here.
A phase 3 confirmatory trial of AMX0035, called PHOENIX, is currently underway. Topline results are expected mid-2024. You can find out more about AMX0035 and PHOENIX on our website.
Phase 3 trial investigating TUDCA ends
3 October 2023
The phase 3 clinical trial investigating the safety and efficacy of tauroursodeoxycholic acid (TUDCA) in people living with ALS has completed. Data analysis will start very soon, with top line results expected to be announced by the end of December 2023. The open-label extension phase, where everyone receives the treatment regardless of whether they were randomised to the placebo group, is ongoing at all centres. You can read more here or find out more about TUDCA here.
MND-SMART stops trialling trazodone and memantine due to lack of benefit
28 September 2023
The independent trial committee for the MND-SMART clinical trial recently reviewed the stage 2 interim analysis for memantine and trazodone. It was decided testing should not continue for either drug as it is highly unlikely that the either drug will show benefit for people living with MND. This decision was based on the fact that there was no significant improvement in the rate of change in the ALSFRS-R scale compared to the placebo – indicating no change in the rate of progression of the disease. As a platform trial, MND-SMART allows for drugs to be removed quickly if they are not showing any benefit. Platform trials also allow for the easy addition of potential new drugs into the trial. There are plans to add an additional three drugs into MND-SMART over the next couple of years.
MND-SMART is still trialling amantadine, which was introduced into the trial in April 2023. There will be an opportunity for people who have been on the trial to re-join MND-SMART and be randomised into the other arms of the trial. You can find out more on MND-SMART’s website.
FDA Advisory Committee vote against the approval of NurOwn in the US
28 September 2023
BrainStorm has announced the outcome of the Food and Drug Administration (FDA) Advisory Committee meeting on NurOwn as a treatment for MND. Overall, when asked the question “Does the data presented demonstrate substantial evidence of effectiveness for the treatment of mild to moderate ALS?” the panel answered no. The panel voted 17 to 1 (and 1 abstain) that the evidence presented did not demonstrate that NurOwn is an effective treatment of mild to moderate ALS. You can read more about the Advisory Committee vote here.
Although the FDA considers the recommendations of its advisory committees, the recommendations of the panel are non-binding. The final decision regarding the approval of the Biologics License Application for NurOwn will be made by the FDA by 8 December 2023. You can read more about NurOwn here.
New funding scheme aiming to accelerate MND research launched
28 September 2023
A new programme aiming to accelerate the pace of research into MND has been launched today by Dementias Platform UK. The MND Translational Accelerator Programme aims to help develop discoveries from the laboratory into potential new treatments, also known as translational research. Researchers can apply for a slice of £6 million funding as part of the Programme when applications open in October 2023. This £6 million investment, funded by the Medical Research Council and the National Institute for Health Research (NIHR), is part of the government’s Department of Health and Social Care’s £50 million commitment to research in MND. Head to the website to learn more about the funding and how to apply.
New investment into MND Association funded research could help take new potential treatment into clinical trial
27 September 2023
Research that was initiated by a research grant funded by the MND Association and is currently being supported through a joint project with LifeArc has led to a spinout company from the University of Sheffield. This spinout company, called Crucible Therapeutics, has recently received £5 million investment from Northern Gritsone and Argobio Studio. Crucible Therapeutics aims to develop new potential gene therapies for the most common genetic form of MND and FTD, known as C9orf72.
Funding from the MND Association and LifeArc is currently supporting the development of the gene therapy at the University of Sheffield. The therapy aims to reduce the effect of a protein, known as SRSF1, which has been found to cause toxic RNA molecules to move to the wrong place within the cell. It is hoped that preventing the RNA molecules from moving to the wrong place will have a therapeutic effect in people with MND/FTD. Crucible Therapeutics will work in collaboration with the University of Sheffield and the Cell and Gene Therapy Catapult (CGT Catapult) in the development of this gene therapy. The new investment aims to help push this work into early clinical trials. You can read more about the research involved in this project here or more about the new investment here.
Additional data from CNM-Au8 clinical trials suggests potential survival benefit
27 September 2023
Clene Nanoscience has reported additional data from both clinical trials of CNM-Au8, including the RESCUE-ALS trial and the HEALEY ALS Platform. The additional data from the RESCUE-ALS trial includes long-term follow-up (2 years) from the open-label extension part of the trial. The open-label extension is where everyone involved in the trial gets access to the treatment, regardless of whether they received the placebo in the randomised part of the trial. This data suggested a significant average survival benefit of 19.3 months for those who initially received the treatment compared to placebo. The full results are expected to be published soon. You can read more about the RESCUE-ALS results here.
The data from the HEALEY ALS Platform trial also highlighted a potential survival benefit of CNM-Au8. This data is described as ‘post hoc’ which means this analysis was completed after the initial data from the trial was seen by the researchers. Post hoc analysis normally allows researchers to gain additional information which could then be further confirmed in another clinical trial. The researchers used the PRO-ACT database, which is a large database of information from people living with MND in the United States, and compared it to the survival data in the trial. This comparison showed a significant improvement in survival, with a 49% decrease in the risk of death. This means that more people were still alive at the end of the trial who received treatment compared to the survival data seen in the real-world database. You can read more about the HEALEY Platform trial results here.
CNM-Au8 is an oral-suspension of gold nanocrystals, which has been shown to improve motor neurone survival in laboratory studies. You can read more about CNM-Au8 here.
New phase 1 clinical trial tests a potential device which may slow progression of MND
14 September 2023
PathMaker has announced that the launch of a phase 1 trial to test their device called the MyoRegulator for the time in people with MND. This device aims to reduce hyperexcitability which is an abnormal and more frequent sending of electrical signals and this can cause damage to the neurons over time. It is thought that reducing hyperexcitability may help to preserve motor neuron health and slow disease progression. MyoRegulator is non-invasive and is delivered through the skin to send messages to neurons in the spinal cord.
The phase 1 trial is an open label trial, meaning that everyone in the trial will test the device, and will recruit people with MND in the US to test the safety of this device and see whether it may be practical to use and beneficial for people with MND. You can read more here.
Researchers awarded first funding from the MND Association's Pre-Fellowship scheme
12 September 2023
Two UK researchers have been announced as the first to receive funding through the MND Association's new Pre-Fellowship scheme. The first-of-its-kind Pre-Fellowship Scheme for MND is funded by the MND Association and administered by MND Scotland. Dr Alannah Mole, University of Sheffield, and Dr Emily Carroll, University of Oxford have been selected to receive the funding. The scheme provides 12-18 months of 'pump priming' funds to bridge a funding gap and aims to help retain early career researchers who have chosen to investigate MND. This scheme will allow the award holders to gather data needed to show the potential of their research, which could lead to longer-term fellowships. Dr Mole's research will examine the sequence and timing of events that ultimately lead to nerve cell failure in MND. While Dr Carroll will look at existing drugs, which are currently used to treat other conditions, to see whether they could be effective in the treatment of MND. You can read more about the research projects here.
New treatment candidate shown to reduce inflammation in MND
7 September 2023
A new potential therapy called AB126, being developed by Aruna Bio, is designed to reduce inflammation and promote motor neuron protection and survival. This therapy consists of exosomes which are small packets of proteins and other compounds needed for cells to communicate with each other. The AB126 exosomes are made from brain stem cells and is thought to increase the growth and repair of neurons.
In models of MND, AB126 was found to reduce inflammation and a biological marker of neuron damage known as Neurofilament light chain (NfL). This early testing shows promising results for continuing to develop and test AB126 to fully understand whether it may be beneficial as a treatment for MND. You can read more here.
Replacement motor neurones could restore muscle function in MND
22 August 2023
Researchers from University College London have been able to use replacement motor neurones in mice with nerve injuries. These replacement motor neurones can then be activated by light and improve muscle function. Researchers found that the replacement motor neurones needed regular activation with the light to help start to improve muscle function. This research suggests that damaged motor neurones can be bypassed, and muscles can be activated by using replacement motor neurones. The researchers state there are still many challenges to be overcome before this approach could be used in people with MND, including whether attaching the replacement motor neurones would work with human motor neurones. You can read more here.
Update from clinical trial investigating daily dose of Oral Edaravone
7 August 2023
Mitsubishi Tanabe Pharma America have announced that the Phase 3b clinical trial investigating a new dosing regime for Oral Edaravone (MT-1186) will be discontinued. Oral edaravone is already approved for the treatment of MND in the US with a on/off dosing regimen administered in 28-day cycles. This trial was designed to determine if taking a daily dose of oral edaravone would be more beneficial for people with MND. Pre-planned interim analysis from the trial showed that if the trial continued there is low chance that the daily dose would be more beneficial than the on/off 28-day cycle dose. The trial used the ALSFRS-R scale to measure the efficacy of the drug. While the trial investigating this dosing regime has been stopped, preliminary findings suggest that the efficacy of the on/off 28-day cycle dose is consistent with the Phase 3 trial which supported the FDA approval. You can read more here or find out about the Phase 3b trial here.
In Europe, a Phase 3 trial (ADORE) is testing a different formulation of Oral Edarvone, known as FNP122. This trial is also testing a once-daily dose of the potential treatment. The trial has closed for recruitment in 2022 and topline results are expected in 2024. You can read more about the ADORE trial here.
Immune cells could be a target for MND therapy
2 August 2023
Researchers have found that a protein called alpha-5 integrin is found at consistently high levels in immune cells found close to damaged motor neurones in people with MND. When researchers used an antibody to block the protein, in mouse models, they found it slowed disease progression and improved motor function.
Immune cells are essential for maintaining the health of the brain and spinal cord, but can be found to be overactive in MND, causing inflammation and damage to motor neurones. The researchers found that the immune cells which had high levels of alpha-5 integrin also produced more inflammatory molecules. Integrins are found on the surface of cells and are involved in helping cells attach to nearby cells. They also receive and transmit signals that tell the cells how to behave. The researchers proposed that the immune cells, known as macrophages, with high levels of alpha-5 integrin may recruit other immune cells and worsen inflammation. Further work is now needed to gather more evidence on the benefit of the antibody. You can read more here.