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 annals of ALS clinical trials is strewn with failed studies. Only two out of more than 70 clinical trials have been positive, and even these showed only very modest benefit. Is this dismal record strictly due to the extraordinary complexity of neurodegenerative disease in general, and ALS in particular? Or is it due to methodological flaws that could be repaired?”
Robert G Miller, Professor of Neurology, Stanford University
Although there is not much we can do about disease complexity, improving the way treatments are trialed is something that can be achieved. Imagine a world without clinical trials, where independent companies or individuals would be allowed to sell their self-made ‘drugs’ without any evidence that they were ever used on anyone with the disease, let alone that they would improve one’s condition. No one would know what the drug is (which could simply be a water solution), how it works and whether as soon as the drug is taken, we would be poisoned.
Thankfully, this is not the case and clinical trials, although not perfect, are considered the gold standard for approving any treatment. However, there are still some improvements that can be done to make trials easier to access and provide more accurate estimates of drugs’ effectiveness much faster.
Is it possible that a drug that treats congestive heart failure could improve respiration in people with MND? Or that a drug used to treat cancer could reduce motor neuron inflammation and possibly slow progression of the disease? In this blog we take a look at drug repurposing – using a drug developed to treat a particular disease to treat another that is unrelated – what it is, and what it might mean for people living with MND.Read More »
In November 2018 the Home Office released a draft Guideline scope for Cannabis-based products for medicinal use in which they announced that specialist doctors (like consultant neurologists) on the Special Register of the General Medical Council will be able to prescribe cannabis-based medicinal products to some patients. Before this, the only cannabis-based medicines licensed for use in the UK were nabiximols (Sativex), used as a treatment for spasticity (where muscles are continuously contracted, causing stiffness or tightness of the muscles, interfering with normal movement and speech), in multiple sclerosis (MS).Read More »
There has recently been a flood of news stories on the outcomes of the Australian Phase 1 clinical trial investigating Copper ATSM (CuATSM) which is a small man-made compound that can selectively deliver copper to cells. The results were first presented at our International Symposium in Glasgow back in December.
MND is a terrible disease and anyone affected by it is looking for good news. We really hope that CuATSM will provide a new treatment for MND that is going to have a positive effect on people’s disease progression.
However, CuATSM is not yet at a stage where a clinician can prescribe it as a treatment. Drug development is a long journey, where any drug has to pass important rigorous checks before approval as a medicine. This trial is an important ‘first’ in the drug development process.
This blog is part of the ‘Highlights from Glasgow’ collection of articles, where you can read about the content of some of the talks and posters presented at the 29th International Symposium on ALS/MND.
In the Clinical trials and trial design (4B) session we heard from two speakers looking at ways to improve current design of clinical trials. In his plenary talk, Mahesh Parmar (C20) provided his perspective on the necessity of changes from his experience working on cancer trials, highlighting that any efforts to improve clinical trials should be focused on Phase 3 where the most money and time is spent. One solution that stuck with a lot of clinicians attending Prof Parmar’s talk was the design used in the STAMPEDE trial, a large clinical trial assessing effectiveness of new treatments for people affected by prostate cancer, which has been running since 2005. The innovation of this approach is the ongoing protocol that allows to test multiple treatments within the same established clinical trial, allowing new drug candidates to be tested (relatively) straight away, avoiding the creation of a brand new clinical trial. This design improves efficacy of testing new treatments, systematic approach to testing, and access to a large pool of participants who could take part in multiple treatment trials over time.
Brian Dickie, the Director of Research Development at the MND Association said: “Prof Parmar’s presentation generated a lot of interest amongst clinicians who are regularly involved in MND trials and there was a strong feeling that this is the direction that we need to be taking with MND as it could increase the efficiency and reduce the cost. That said, it will take a while to put the building blocks in place and we certainly wouldn’t want to hold up trials that are already in advances stages of planning, so I would expect to see a gradual introduction of changes to trials design over the coming years.”
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.Read More »
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.Read More »
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.Read More »
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.Read More »