Tirasemtiv not found effective for treatment of MND

In their official press release published on 21 November 2017, Cytokinetics Inc. announced that they will not be continuing work on tirasemtiv after disappointing results in the latest Phase 3 clinical trial. The trial, known under the acronym ‘VITALITY-ALS’, tested whether the drug has a beneficial effect on the breathing function and muscle strength of people with MND. This is very unfortunate news for everyone affected by the disease, however, Cytokinetics are already testing another compound with the hope that this will be more effective and better tolerated than tirasemtiv.

Tirasemtiv is a drug that aims to improve quality of life of people living with MND by increasing strength of their skeletal muscles (controlling body motion and posture) and therefore postponing muscle fatigue. It compensates for the missing nerve signal from a motor neurone to a muscle that instructs it to contract. Tirasemtiv activates a protein called troponin by increasing its sensitivity to calcium, which is crucial for muscle contraction. Continue reading

Lithium revisited: Is there a baby in the bathwater?

At last year’s Airlie House workshop to develop new ALS/MND Clinical Trial Guidelines the focus was, of course, on MND, but there was also important input and learning from outside the field.

One of the most fascinating presentations was from an oncologist who was explaining how detailed genetic analysis of tumours was leading to an understanding of why some experimental cancer drugs appeared to only work in a small subgroup of patients. The take home message from the cancer field was that there should be more effort made in future MND trials to identify and analyse smaller subgroups of patients, in case a potentially positive effect might be missed.

A new research paper, published in the journal Neurology, raises some intriguing findings from the trials of the drug lithium that were carried out several years ago. Lithium generated a lot of excitement when researchers in Italy reported a positive effect of the drug in the SOD1 mouse model of MND. Almost as an afterthought, their research paper mentioned that they had tested the drug in a small short-term trial in patients and it appeared to have some effect. Continue reading

Lighthouse Project shines a beacon on HERVs and their role in ALS

There is recent evidence to suggest that Human Endogenous Retroviruses (HERVs) may be involved in amyotrophic lateral sclerosis (ALS). HERV-K has been directly linked to motor neurone damage and has been found in the brain tissue of patients with ALS.

The MND Association recently awarded a small grant to fund part of the ‘Lighthouse Project’ which is investigating the safety and any beneficial effects of an antiretroviral drug on ALS symptoms. Continue reading

Edaravone – a month on since the FDA announcement

It’s been over a month since the announcement by the FDA of their decision to licence edaravone / Radicava for people with MND in the USA. The speed of the FDA’s decision took the drug company MT Pharma and the MND research community by suprise. It is encouraging that edaravone has been licenced to treat MND after two decades of failed drug trials. Since the FDA announcement the effects of the drug and what it means for people with MND has been extensively discussed and some of the trial data has been published.

This blog is an update on what studies have been done on edaravone and the likelihood of people with MND noticing a beneficial effect if they were to receive it. 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

Edaravone (Radicava) approved to treat MND in USA – what does this mean for people with MND in the UK

On Friday 5 May in America, the FDA, the organisation that approves drugs, announced that they’d granted a licence for the drug known as a Edaravone (to be marketed as Radicava ) for the treatment of MND. It’s unexpected news and we’re currently working out what this means for people with MND in the UK. Below is more information on what we know so far:

Continue reading

Prize winning posters in Dublin

As well as all the networking, debate and new information being shared, the International Symposium on ALS/MND is also a time to celebrate achievements by the giving of awards. The Biomedical and Clinical poster prizes are an opportunity to recognise and celebrate the excellent research and clinical practice being conducted by those early in their career.

Now in its fourth year we hope that the poster prizes will help give the winners career a boost, and give them the encouragement and motivation to continue in MND/ALS research.poster-prize-winners-low-res This year the Panel selected an international group of winners: Dr Albert Lee from Australia and Elsa Tremblay from Canada were jointly awarded the Biomedical poster prize and Ruben van Eijk from The Netherlands won the Clinical poster prize. Each winner received a certificate and a glass engraved paperweight.

The prize winning research ranged from understanding the consequences of a newly discovered gene mutation linked to MND, to why the junction between nerves and muscles is one of the earliest signs of motor neurone damage, to a new statistical analysis to make clinical trials quicker and more efficient. Below I’ve explained more about the research that the winners presented. Continue reading

ALS/MND Clinical Trial Guidelines: your opportunity to comment!

A few months ago we wrote an article about the ALS Clinical Trials Workshop which took place in Virginia, USA. Since then the Guidelines Working Groups have been busy turning the large number of issues debated into a first draft of a new set of guidelines. This is open for comment from 1- 31 August.

The guidelines will be posted on this website, and comments can be sent to guidelines.public.comments@gmail.com.

The guidelines are divided into sections:

  • Preclinical studies
  • Study design and biological and phenotypic heterogeneity
  • Outcome measures
  • Therapeutic / Symptomatic interventions in clinical trials
  • Patient recruitment and retention
  • Biomarkers
  • Different trial phases and beyond – (there are two sections on this)

Within each of these sections, there are many recommendations. The Clinical Trials Guidelines Investigators want to ensure that all interested people and stakeholders have an opportunity to provide input – whether you are a researcher, clinician or person with MND.

Thank you very much for your help.

For more information, please see a copy of their press release below: Continue reading

Correcting the early damage seen in MND

Previous research in humans and zebrafish has shown that before symptoms arise in MND, early changes occur in the interneurones. This type of nerve cell provide a link between the upper and lower motor neurones in the brain and spinal cord.

The job of one type of interneurone (called inhibitory interneurones) is to apply the brakes on motor neurones. They work just like brakes on a bike stop the wheels from moving.

The interneurones control when chemical signals/messages (or action potentials) can be passed along the nerve cell. In MND these brakes are less effective (so to use the bike analogy, the brakes might be rusty or not connected properly).

Interneurones are being studied in more detail in a project led by Dr Jonathan McDearmid (University of Leicester), in collaboration with Dr Tennore Ramesh and Prof Dame Pamela Shaw (Sheffield Institute for Translational Neuroscience) (our reference: 835-791). Continue reading

Protecting motor neurones against oxidative stress in MND

During the early stages of MND it is proposed that motor neurones are more susceptible to an imbalance of oxygen within the cells, known as oxidative stress. Prof Dame Kay Davies, at the University of Oxford, has previously shown that increasing the levels of the gene Oxr1 can protect motor neurones from death caused by oxidative stress and delay MND in mice. You can read about this work here. Continue reading