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

Could a Diabetes drug be useful in treating MND?

Today we announce a new collaboration for a preclinical research study on the diabetes drug liraglutide, in the hope that positive results will lead to a clinical trial in MND. Here’s a little more about the rationale behind the study.

The idea that drugs licensed for one disease may have some use in another completely different disease is not new, but it has gained much more attention in recent years. Researchers are developing a new understanding of disease processes, leading to new ‘drug repurposing’ opportunities, with the additional potential to reduce the time and cost of drug development.

Significant advances in genetics and molecular biology in recent years have greatly increased our understanding of the pivotal, carefully balanced cellular processes that usually keep motor neurons healthy but, when disrupted, can cause a cascade of degeneration leading ultimately to their death. Continue reading

Irish angiogenin research leads to promising results

Angiogenin was discovered as a cause of MND for a small number of families affected by the inherited form of MND in 2006. Since then, research has been ongoing to better understand the role of angiogenin and to see if we can use this information to develop future treatments.

This week, we learnt of two inter-woven news stories related to angiogenin. One was related to a new biological finding of the vital role that angiogenin plays and the second expands on this work and led to the testing of angiogenin in mice that model MND. Prof Jochen Prehn leads the Irish research group who made these findings from Royal College of Surgeons in Ireland.

Angiogenin to the rescue!

Through their research, the Irish group identified that angiogenin acts as an emergency service call from our motor neurones to support cells. The findings were published in the Journal of Neuroscience and help us to better understand both the biology of angiogenin and how we can use this to develop future treatments for MND.

In essence, the research group outlined the following pathway for how angiogenin works and how it can go wrong:

When motor neurones are in trouble, they send out angiogenin as their ‘999’ call. This ‘call’ is received by our support cells – the neighbouring astrocytes (so called because they are star shaped).

As angiogenin whizzes it’s way between the outside of the motor neurone and the astrocyte, it needs to find a particular ‘door’ to enter. Cells are quite particular as to what they let inside, so no ‘Joe Bloggs’ can simply walk into a cell unless it has permission to pass (the exception being if it’s something really small!).

As angiogenin plays an emergency service role, it has a pass to be led into the astrocyte. Through this study, the research group were able to specify exactly which ‘gatekeepers’ and doors are used by angiogenin to enter the astrocyte.

Once inside the astrocyte, angiogenin goes into the control centre of the cell – the nucleus. Here, it rolls up its sleeves and starts editing copies of (supposedly, emergency service) genes to help the astrocyte to create more supportive proteins. We don’t yet know what these genes are, but it was declared as a next step for the project in the published paper.

In MND cells with mistakes in the angiogenin gene, it’s function as an editor of gene copies doesn’t happen. Angiogenin is still created in the motor neurone, and passes through into the astrocyte, but it’s supportive function isn’t happening.

This study therefore raises the possibility that angiogenin could be developed and tested further as a possible future treatment for MND to help this supportive function continue.

Testing angiogenin in mice

The second angiogenin story relates to a presentation that was given at the recent European Network for the Cure of ALS (ENCALS) meeting in Dublin by Prof Prehn’s group.

As a follow on to their previous work, Prof Prehn’s research group tested the effectiveness of angiogenin as a treatment for MND in mice. These are called pre-clinical studies, and are essential to provide enough evidence to move to human clinical trials.

In a similar move to our Cogane study, the group have identified through a rigorous MND mouse study that angiogenin could be a promising treatment. Overall, they concluded that it prolongs life by 10 days in mice (which is more effective than riluzole), increased the survival rates of motor neurones, and delayed the progression of symptoms when given after symptom onset.

This study will need to be published and verified in another model, or by another lab following preclinical guidelines to ensure that these results are reliable. After that, the next steps would be for human clinical trials to be initiated. This means that angiogenin could start to be tested in humans in the next few years.

In summary…

Together, these studies prove the value in better understanding the causes of MND, even when the genetic mistake may only cause the disease for a small number of families.

Being able to move a biological finding from the laboratory toward the clinic is always encouraging news.

All in all, it’s great news for the first day of our month of optimism!

Cogane produces encouraging results in MND Association-funded study

Prof Linda Greensmith

Prof Linda Greensmith

Thanks to funding and some strategic ‘match-making’ by the MND Association, a new drug may have taken one step closer to beginning clinical trials in MND after producing promising results in an animal model of the disease.

The drug, known as Cogane, was developed by the biotechnology company Phytopharm. It had already demonstrated in laboratory tests that it could help to protect neurones by promoting the production of natural, nerve nourishing substances called neurotrophic factors and early animal testing had hinted at its potential beneficial effects in MND. However, its journey towards clinical testing in MND had hit a road block because it hadn’t been extensively put through its paces in large numbers of the most widely used animal model of the disease, the SOD1 mouse. Without robust data from this model, there would have been little to encourage further investment in Cogane’s development.

So up stepped the Association to introduce Phytopharm to Professor Linda Greensmith at University College London, a leading MND researcher with considerable expertise in SOD1 mouse testing. With funding from the Association, Prof Greensmith and her team were able to conduct a rigorous study of the effects of Cogane, administered to the mice after they had developed MND-like symptoms.

The drug produced some significant improvements in muscle strength and motor neurone survival and managed to produce positive effects even in mice that had reached the later stages of the disease. To give more substance to these preliminary but very encouraging results, the research team will now go on to the painstaking work of examining more closely Cogane’s effects on the motor neurones and other key cells that play a critical role in the progression of MND. 

After the disappointment of the Trophos trial results, it’s great to be able to share some positive news on the drug development front. We know from long experience that it’s wise to limit our excitement over positive results from the mouse model – after all, plenty of drugs have shown promise at this stage and have then gone on to fail in clinical trials. However, Prof Greensmith’s experience and expertise mean that Cogane will have been tested with the utmost rigor. As she herself commented, the results indicate that “Cogane has significant potential as a therapy for ALS and merits further evaluation”.  We don’t yet know what Phytopharm’s next steps will be – these may become clearer once the more detailed data from Prof Greensmith’s work have been published, which could take the best part of a year. Let’s hope that we have a given Cogane enough of a boost to push it out of the drug development ‘doldrums’.

Read the Phytopharm press release.