Parkinson’s UK research highlights for 2013

Now that 2014 has arrived, this is a good time to reflect on 2013 and what we have been achieved. And it was a really busy and productive year for research at Parkinson’s UK. So, here are some of the highlights of what we have achieved.

1. We funded over £5million in research grants

This was our highest amount that we have ever spent on research grants in a single year. It included project grants, innovation grants, career development awards and PhD studentships. All of these were rigorously scrutinised by external review and represent the highest quality cutting-edge research. Further details of the grants awarded can be found on the research website. This brings our total spend on research to over £65million since the charity started.

2. Our GDNF clinical study got underway

Clinical studies carried out almost ten years ago suggested that the Glial Derived Neurotrophic Factor (GDNF) protein may have a protective effect against Parkinson’s and may even reverse its progression by stimulating nerve cells to regrow. However, there were problems with the initial trial design and the drug was withdrawn. In 2012, Parkinson’s UK teamed up with Medgenesis, the North Bristol NHS Trust, and the Cure Parkinson’s Trust to design a new clinical trial.  NBT have been working to develop a new way of delivering the GDNF into the part of the brain affected by Parkinson’s and Medgenesis are providing the drug for the trial. An initial three month trial with six participants took place in the first half of 2013. This was to ensure that the procedure was safe and that the GDNF was being administered to the correct part of the brain at the appropriate concentrations.  Following the success of this “safety phase”, a full study involving 36 participants has now started with people currently being recruited. The study will last 18 months and further details can be found on the Parkinson’s UK website.

3. Participation in clinical trials

Parkinson’s UK is funding two long-term studies of people with Parkinson’s. This involves the recruitment of people who have been diagnosed within the last three years and following the progression of their condition over time. This will help us to really understand how Parkinson’s progresses, how we can diagnose it more accurately at an earlier stage and what the best medications are. Tracking Parkinson’s is the largest study of its kind in the world and aims to recruit 2,400 people with Parkinson’s and 600 first degree relatives (brothers and sisters). Recruitment is taking place at over 50 centres throughout the UK and already we have recruited over 1,800 participants. As part of the Monument Discovery Award, we are recruiting over 1,200 people from the Thames Valley region in a parallel study. The first results from this study have recently been published and these reported age and gender differences in symptoms as well as providing information on non-motor symptoms. We are now working to make the data available to researchers worldwide so that the best use can be made of it.

We have also helped to recruit over 1,300 participants without Parkinson’s for the PRECICT-PD study. This has used changes in the sense of smell as well as finger tapping tests to identify people who may be at higher risk of developing Parkinson’s. These people will then be followed over time to see who may develop Parkinson’s and this information will be key to our identifying people at risk of developing the condition more accurately and at an earlier stage. This research is being carried out by Dr Alastair Noyce who holds one of our career development awards and demonstrates our commitment to investing in the brightest young researchers. The initial results of the study have now been published.

Parkinson’s UK also provides details of current research projects within the UK in which people can take part. These include both clinical and non-clinical research. We are approached on a regular basis by researchers who want to recruit volunteers. We can play a key role by connecting researchers with study volunteers. There are 21 trials currently recruiting and listed on our website.

4. Identifying biomarkers of Parkinson’s

If we are to make an early and accurate diagnosis of Parkinson’s, we need to have reliable “biomarkers” – indicators that somebody has Parkinson’s. These will complement the clinical evaluations that are used primarly at present. One way is to develop a blood test where changes specific for Parkinson’s can be identified. We invited applications from researchers worldwide to submit a proposal to use the technique of proteomics to develop blood markers. After receiving 27 applications from 12 countries, the contract was awarded to Prof Simon Lovestone who has used a similar approach for the study of Alzheimer’s. We have also awarded a large grant to a group at the University of Nottingham to develop new sensitive scanning techniques to help improve our diagnosis of Parkinson’s. Both of these will involve people who have been enrolled into our Tracking and Discovery cohorts.

5. New uses for old drugs

The development of new drugs is extremely expensive and there are a lot of failures. In 2013, less than 40 new drugs were approved for use in Europe. So, it would be much cheaper and more efficient to use an existing drug to treat another condition (called repositioning or repurposing). Parkinson’s UK funded research a few years ago to suggest that exenatide, a drug used to treat diabetes, may help to slow down the development of Parkinson’s using an animal model. Based on these findings, a small clinical trial suggested that this may also be the case in man and a larger study is now underway.  Another project funded by Parkinson’s UK using skin cells from people with Parkinson’s screened 2,000 existing drugs and found that at least one with particular promise called ursodeoxycholic acid (or UDCA). This is a drug used for decades to treat certain forms of liver disease. And we have awarded a career development award to Dr Heather Mortiboys at the University of Sheffield to continue this work.

6. Involvement of people with Parkinson’s

Everything that we do is driven by the needs of people affected by Parkinson’s and it is key that they play an integral part in our research programme. In addition to participation in clinical trials, there are many more ways in which people can become involved in research. Our Research Support Network is a group of over 800 members who have a particular interest in research. Some, for example, help to assess our research grant applications. Others visit our researchers to discuss their researchers while there are also opportunities for people to sit on project steering groups and really shape the research at an early stage. And we regularly host events to which members of the public can come along.

6. Communicating the impact of our research

While it is vital that we continue to fund the highest quality research, it is also important that we ensure that our research is making a real difference, either in the shorter or longer term. In addition to providing us with regular updates on their progress which are rigorously assessed, all of our researchers are required to provide us with details of publications arising from their research, other research funding that arose from work that we funded and other tangible outcomes. We have put this together in a short cartoon video which highlights our outputs as well as in a pictorial form. We also use a variety of communications channels to publicise both the research that we are funding as well as other key discoveries in the field. These include the Parkinson’s UK website, our research magazine Progress, the research pages of The Parkinson magazine, Synapse (our researchers’ newsletter), twitter, facebook and others. It is vital that we keep people updated on all that we are doing and achieving.

7. Our wider influence

In addition to the research that we fund, Parkinson’s UK has had a particular influence within the wider research arena in 2013. Through our active campaigning strategy, we have served as the voice of Parkinson’s research both within the UK and in Europe and we represent people with Parkinson’s at many levels. Our Chief Executive Steve Ford attended the G8 summit on dementia to highlight the importance of dementia for people with Parkinson’s. We are also represented on external bodies such as the Executive Council of the Association of Medical Research Charities, the Medical Research Council Brain Bank Steering Committee and the Parkinson’s Clinical Study Group of the Dementias & Neurodegenerative Diseases Research Network (DeNDRoN). We are frequently invited to attend Parliamentary and other events to promote Parkinson’s research and lobby for increased levels of funding. One of the highlights of the year was the invitation to speak at the Partnering for Cures meeting in New York in November. we were the only European charity presenting and it gave us an opportunity to showcase our research to other research funders and to industry. In particular, we stressed the importance of sharing clinical trial data and this will be a key priority for us in 2014. You can see our presentation here.

8. Looking forward to 2014

There is a lot planned for 2014. In addition to funding new research, we will continue to support our brain bank, the Tracking and Discovery cohorts as well as involving people in research at all levels. As part of this, we have launched a survey to help us identify the top 10 unanswered questions in Parkinson’s research. In addition to helping us to design our 2015-19 research strategy, we will also be able to campaign for the funding of specific areas of research which have been identified by people affected by Parkinson’s in collaboration with healthcare professionals. There will be more announcements of research initiatives and developments and you can catch up with all of our research news on our website.

 

Posted in Research | Leave a comment

Potential earlier access to new medicines?

The Prime Minister published a “Strategy for Life Sciences” in 2011 and one of the recommendations was to investigate the potential of making new drugs available to patients at the earliest possible opportunity. An expert working group was set up to investigate this and to make recommendations on how it could be implemented. This was led by the MHRA with representatives of the pharmaceutical industry, relevant government departments and research-funding charities. I was appointed as a member of the working group to represent Parkinson’s UK.  After a number of meetings, a report was published a couple of weeks ago which has now been submitted to the Government.

There are two main recommendations. The first was the launch of an Early Access to Medicines Scheme. This would be of particular importance for promising unlicensed medicines which are deemed to be safe and efficacious and which would address areas of “high unmet medical need”. This refers particularly to relatively rare conditions for which there are currently no treatments. Because of the library of drugs that is already available for the treatment of Parkinson’s, it’s unlikely that any new drugs would be covered by this programme.

The second recommendation was to develop an Adaptive Licensing Programme. This has already been proposed by the European Medicines Agency (EMA) and guidelines are being prepared. Essentially, medicines which have been shown to be safe and effective in early phase III multi-centre trials would be made available on prescription for people not in the study, but these people would be monitored closely for safety issues such as adverse effects of the drugs. It is likely that such an initiative will come from the EMA as the centralised licensing authority and this will then be implemented in member states (by the MHRA in the UK). It was considered that the existing legislation is sufficiently flexible for such a scheme to be implemented without legislative changes.

There are some examples already available of products which have been fast-tracked through the regulatory process. These are primarily for the treatment of medical conditions that are considered as being sufficiently rare that it would not be possible to access a large enough body of patients to carry out a normal clinical trial. 37 such therapies have been licensed within the EU since 2001. However, some companies said that they were unaware of such a programme, so a further recommendation from the working group was to publicise this pathway more widely within the pharmaceutical industry. There was also the suggestion that industry and the regulatory bodies should consult at an earlier stage to work together on medicine development. This would be of particular importance for novel therapies such as cell and tissue transplants.

So where do we go from here? The report has been submitted to the Government, so we will eagerly await the results. However, as there is a similar initiative planned by the EMA, the Government may be tempted to wait for Europe to take the lead. This is despite the fact that no new legislation would be required to implement the schemes in the UK. We shall await the results eagerly.

Posted in Research | Leave a comment

Emerging therapies for CNS diseases

I recently attended a conference which focussed on the development of new drugs for conditions such as Parkinson's and other neurodegenerative conditions. This included both the biotechnology and pharmaceutical industries as well as external funders such as Parkinson's UK.

A number of interesting themes emerged. Firstly, despite rumours to the contrary, the pharmaceutical industry remains committed to the area of neurodegenerative conditions such as Alzheimer's and Parkinson's. This is despite reports of a significant downsizing of the number of researches employed by the companies in this area. This is due to the emergence of a new strategy for drug development. In the past, the pharmaceutical industry would fund all stages from pre-clinical trials through early clinical trials to the marketing of the drug. This has now changed and the pharmaceutical industry now only gets involved in the process at a much later stage.

So initial research, such as the identification of drug targets or the screening of chemical compounds, usually takes place in academia or in small biotechnology companies. The lead compounds are then brought forward to the pre-clinical stage before initial phase I clinical studies to determine the drug's safety profile. All of this is likely to be carried out by small companies or in academia. There is an increasing trend for research funding organisations such as Parkinson's UK to support research within this space.

Once there is evidence that the drug is safe, and initial phase II "proof of concept" studies have taken place - does the drug have any clinical benefit - the pharma companies may be interested in purchasing the rights to the drug and then invest in the costly phase III multi-centre clinical trials. This provides a return on investment for the smaller companies while the larger pharma companies don't have to take the risk of investment in the early stages of drug development.

This may appear to be a a logical progression and in a lot of cases, it works. However, it is dependent on the ability of the smaller biotech companies to identify what targets and chemical compounds will be of interest for the pharma industry who will ultimately be purchasing the rights to the drug. The companies also carry out an assessment of the market. At the moment, there are over 20 drugs to treat the symptoms of Parkinson's with only four for Alzheimer's. And in the UK, there are 450,000 people with Alzheimer's and 127,000 with Parkinson's. So it's not difficult to work out where the priority is. Another area of interest is conditions where there are no therapies available such as Huntington's or MND.

From a Parkinson's perspective, while we would like to see investment going into the development of drugs which will treat the condition rather than the symptoms. However, the clinical efficacy of such drugs would be extremely difficult to measure, especially considering that people are likely to remain on their symptomatic medication while being treated with the drug that modify the progression of the condition. We also know that the placebo effect has a significant role in Parkinson's. So, based on clinical tests, it will be very difficult to differentiate between symptomatic and disease-modifying effects. For this, we need reliable biomarkers which can be quantified and provide an indication of the progression of the death of nerve cells. The "Tracking Parkinson's" study will provide us with a vast amount of information that may help us to identify such biomarkers.

So, despite the apparent lack of progress in this area, there is still cause for optimism. Funders such as Parkinson's UK can play a key role, by supporting early-stage research to understand the basis of the condition, the identification of biomarkers as well as campaigning for a continues investment in the area.

Posted in Research | Leave a comment

Increase in animal research – what does it mean?

Last week, it was announced that the number of animals used in medical research in the UK in 2012 had increased by 8%. This comes at a time when there is a lot of pressure on researchers to actually decrease the use of in vivo studies that are carried out and to move towards the use of alternatives. In particular, we are actively promoting the 3Rs – to reduce, refine and replace the use of animals in medicine.  However, a detailed analysis of the figures showed that the primary reason for the increase was the use of genetically-modified animals, particularly rodents.

 

Conditions such as Parkinson’s are extremely complex and while we can use model systems, such as nerve cells grown in a dish, to study the condition, we need to remember that the brain is three dimensional and that there are many different types of cells. Looking at one type alone will only provide us with a certain amount of information but if we are to really understand – and move closer to a cure for – conditions such as Parkinson’s, we then need to study the whole brain. We also need to consider the fact that other parts of the body may also be affected by the condition.

 

In order to study what happens in the brains of people with Parkinson’s, we need a good model system. In the past couple of years, we have made great strides in our understanding of the condition. In particular, the genome-wide association studies (GWAS) identified genes that may increase the risk of developing Parkinson’s. We also know about external factors such as organophosphate pesticides. So we can put these together. We manipulate the animal’s genetic makeup and treat them with low doses of pesticides. We are now developing models where nerve cells die in specific areas of the brain in a similar manner to those observed in Parkinson’s. This means that, for the first time, we can screen for drugs that may slow down, halt or even reverse the progression of the condition.

 

Many researchers are using subtle differences in their approach in order to determine what will be the best model. When this has been agreed, we expect to see a decrease in the number of animals used as rather than trying to develop the best model, we will be able to use one. This will bring us closer to a cure.

Posted in Research | Leave a comment

Vitamin D and Parkinson’s

A recent report has suggested that vitamin D may have a neuroprotective effect for people with Parkinson’s and taking vitamin D dietary supplements may slow down the progression of the condition. The study compared the development of Parkinson’s symptoms between a group who had received a vitamin D3 supplement and an untreated group. The study showed that people who took the vitamin supplement had a slower rate of symptom progression. However, the researchers said that they couldn’t discount the fact that this was a general effect of the vitamin supplement on ageing and age-related changes in muscle and bone rather than being a Parkinson’s specific effect.

However, previous studies have suggested that people with Parkinson’s may have lower vitamin D level than people without the condition and are more susceptible to develop conditions such as osteoporosis. This may help to explain why additional vitamin D supplements may appear be of benefit for people with Parkinson’s as they would bring levels back to normal.

This study underlines the importance of diet for conditions such as Parkinson’s and how something as simple as ensuring correct vitamin levels can make a big difference to your health. But it may not be necessary to take vitamin supplements as a balanced diet is also likely to give you the recommended daily amount. So it’s important to consult a dietician. They will assess your diet as well as well as advising on any additional supplements that you may need. In most cases, a modification of diet is usually sufficient. You can find out more from the Parkinson’s UK information booklet which gives advice about various aspects of diet for people with Parkinson’s.

Posted in Research | Tagged , , , , | Leave a comment