Friday, 22 April 2016

My Views on Drug Repurposing Conference

So, the last 3 posts have reported what I heard at the conference, and I thought it appropriate to reflect on this and record my views on what I heard.

Hidden Costs

I think that the most powerful thing was the "hidden costs of rare diseases" from Matt Hammond:

  • Psychological
  • Time (travelling, seeing professionals etc.)
  • Finance (travelling)
  • Missing out (on other activities and events)
  • Form filling (it seems there a lot of forms in some cases)
  • Loneliness (being the only one in your situation)
  • The need to plan everything (because of the effects of the disease) 

Matts story was very powerful, and you could feel everyone in the room being affected by the emotional roller-coaster he described. It made me realise the benefits of having a quick and certain diagnosis, and I'm quite pleased I dont have all that uncertainty and delay in getting one.

Drug Repurposing

In terms of drug repurposing, I understand the process that is gone through. I hadn't realised quite the extent of drug re-purposing, and this is done because repurposing is cheaper, quicker and less risky. Although, there doesn't appear to be quite the same incentive to do this as there is for developing a new drug. The main thing to take away is the need to collaborate, most of the papers described that collaboration was needed between the different people involved in the chain. There are several steps:

1) Identify a need.
Firstly, it is necessary to define a need for a new drug. This is where the collaboration between patients, patient groups and clinicians is important. There needs to be sufficient interest in an issue for researchers to look at it, and this is where patient groups can come in very useful by keeping on top of research activities and knowing about patients with condition to (potentially) have a sample of real-world patients who are interested in taking part in research trials.

2) Look for solutions.
With a need in mind it becomes necessary for researchers/clinicians to look for solutions to the need. Several different approaches were described. At one end of the scale the knowledge of the clinician about the need can be used to look through existing information to identify candidates. At the other end of the scale computers are used to search through database libraries of molecules/drugs for candidates. It is a positive that the drug companies/pharma are getting involved with sharing their libraries of molecules/drugs with researchers. 

3) Gathering evidence.
The candidate drugs/molecules then have to be examined to ensure that they are safe and if so, tests and investigations can be made to identify the ones with the greatest potential. If the evidence does not demonstrate improvements in patients then it is necessary to set up a trial.

4) Trials.
Often a trial is needed in order to provide evidence that the drug is safe to use and gives results. Sometimes there will need to be a balance struck between improvements gained and negative side effects. Depending on funding and other constraints the trial may be large or small. Once successful trials are reported, this informs the medical community and the treatment can spread. Issues with trials revolve around getting the right population of patients to take part and their distance from the research centre. Sometimes it is a combination of therapies which gives good results.

Data Sources

I was interested to hear about the different work on data sources, with different tools extracting information from papers in order to allow them to be searched in a database. Two different examples were given, and I particularly like the healx one: .

Sharing Results

One thing which came up a few times in presentations was about how it is generally only successful trials which are published/publicised. In terms of drug repurposing it is perhaps useful to see unsuccessful trial results to allow the safety/function of drugs to be evaluated for other purposes.


Naturally, researchers need to be paid to work, and there is the issue of funding for such work. There is not the same commercial drivers for funding as there are for new drug discoveries, and that is another aspect where collaboration is needed. Often, the patient groups raise money and provide funding, and often deals can be done with the drug manufacturers to get the drugs needed and information about them for trials at a reasonable price (or free). Various research organisations and drug companies are joining forces to be able to run/organise/fund research projects.

Student Essay Competition

One other thing which I felt was really good was the student essay competition. At the conference the awards were presented. You can see about this, and download the essays on the findacure website. As I write this is on page 2 of their news, but I suspect that will soon enough drop to a later page. Interesting stuff!


In conclusion I found the day really useful, and thanks to the UK HSP support group for paying for my ticket! There were also lots of interesting people to talk to in the coffee breaks and it was good to find out more about what happens. Many of the companies present at the event were based in Cambridge, which is my home town! I think that the role of patient groups in understanding what research is being done and sharing that information with their members is important, as is feeding back real world experience/problems to the researchers so they can potentially capture some of this in their research design. Social media seems to be a very important resource for promoting and sharing information, and I'm pleased to report what I heard and saw in order to share this information with you.

Thursday, 21 April 2016

Drug Repurposing Conference, Part 3, London - 29th Feb 2016

On 29th Feb I had the pleasure of going to the Findacure Drug Repurposing for Rare Diseases conference which was held at the Royal Institution in London.  My notes on this conference will take up a few posts. This is part 3 of 3. Part 1 is here. Part 2 is here.

Dr Jack Scannel of Innogen Institute at the University of Edinburgh talked about the case for user led innovation. Scientists have survivor bias - they over-estimate the performance and nobody hears about the 9 out of 10 failures to get to the success. Nobody knows which drugs will sell well, and nobody knows what new drugs will be used for.

He described a paper by DeMonaco from 2006: The Major Role of Clinicians in the Discovery of Off-Label Drug Therapies This paper describes a study into new uses identified over 5 years for drugs introduced in 1998.

29 new drugs were introduced in 1998, and of these new uses were found for 22 of them. In total 143 new applications for those drugs were identified, 82 of these were field based discoveries based on looking at the reporting of the studies, and 57 were led by the laboratory. The paper looks at the field discoveries and reported that 60% of the applications were as a result of a clinician understanding the mechanism of the drug, some 11% were serendipitous discoveries, with the remaining 29% found some other way.

Drug repurposing can be for both common and rare diseases. Even with trials for common diseases clinical trials often don't tell enough about the real world populations who might use the drugs. The issue is how to sort out a trial for diseases with a small patient population.

Jacks key points were that:

  • User-led innovation should be incentivised
  • The would maximise the amount of safe chemicals available
  •  The process reduces timescales
  • The process reduces the demands for phase 3 clinical trials
  • This should improve the ability to track and manage information. 
He observed that often the 2nd, 3rd or 4th use for drugs can be better than the original use.

People can find out about clinical trials at

The last paper of the day was by Dr Victoria Parker at Addenbrookes Hospital, Cambridge.  She talked about repurposing sirolimus for rare mosaic overgrowth disorders. The elephant man has mosaic overgrowth. There is a protein which is working too much, and the objective is to find a drug to turn off the protein.

The drug sirolimus was one example of a potential drug which was shown to work at low concentrations. They set up an open label, uncontrolled, non-randomised pilot trial with 10 patients from the UK. It took over a year to get the trial set up. Victoria described some of the challenges.

As mosaic overgrowth is a rare disease there is a limited overview, and not enough data to statistically justify a randomised controlled trial. The patients were scattered across the UK, so collaboration was needed in the trial design. NHS trusts have no capacity to undertake blood tests, and GPs need approvals to do so. Therefore the trial had to be designed to minimise the study interventions (blood tests), and private sector involvement was needed. 

Funding was the next challenge. The list of costs included: Staff time, a database for the results, the drug itself (and any placebos), shipping costs for the drug, imaging and blood test costs, insurance and pharmacy fees. Pfizer agreed to provide the drug free of charge, the determined that the database could simply be a spreadsheet, and it was cheaper for them to get insurance for 3 separate trials in single locations than a single policy for a multi-centre trial. Overall, the costs were reduced from an initial estimate of £150k down to £60-70k.

Victorias last points were about a revision to the EU Clinical Trials Directive around "low intervention trials" which have minimal additional risk, and therefore "less stringent rules". These come into play from 2018.

There was also a set of lightning talks - each for 5 miutes.

Ravi Jandhyala (Evidence for Access) described that research into treeatments for rare diseases is difficult. Studies have to trade between; Small number of subjects, requirements of randomised controlled trials, high attrition rates and long study durations. Judgement is needed in trial design, and should make use of real world experience, which involves looking at the evidence in the population, the characteristics of the patients and the identification of the patients. Focus on the patient is key.

Dr Julia Ambler (Sparks) outlined their expertise in awarding and managing grants for childrens medical research. They have the greatest chance of making an effort, researchers know where they money comes from, donors know where their money has gone and progress news is shared. Overall they aim to avoid duplication, save time/money and invest in quality research. They also support fundraising activites.

Dr Alan Rothaul (Re-Pharm) described how it is possible to use a computer model to hunt for rare disease treatment candidates - computer aided chemistry. For any target that is identified it is necessary to understand the biology, and then to look through the database for candidate. They look at the 2D and 3D shapes and the field point representation of the drug and compare it with the target. With a match, a proof of concept is obtained which is the optimised and taken forward for development. He described a case where out of 2500 molecules they had 25 close hits, which resulted in 6 trials, identifying one lead compound, which they are tring to move forwards.

Heather Band (Batten Disease Family Association) described Batten disease and how research into drug repurposing is using zebra fish. She observed that family groups are often the starting point for patient groups.

Jane Reed (Linguamatics) described a text mining tool that uses natural language processing to extract chemical, gene and action information from text. However, she notes that the language used in medical texts if no common and it is difficult to get information out.

Richard Smith (Healx) described an on-line tool which allows people to track rare disease research. There are around 1 million papers published per year, and around 100 thousand mention a rare/orphan disease. The tool aims to understand the hierarchy of the papers, and presents a summary of medical information and allows data to be filtered.

These are my key points from the panel discussion:

The difference between off-label and approved drugs for the patient is often about reimbursement,

Routes to off label drugs in the UK is either through GP or hospital, but varies throughout the UK.

Randomised Controlled Trials are often not representative of the typical population.

Patient groups are often good at making sure that trials are valid/representative. 

Combination therapies (i.e. taking more than one treatment at once) can be effective.

Randomised Controlled Trials are not necessarily required for orphan drugs.

Wednesday, 20 April 2016

Drug Repurposing Conference, Part 2, London - 29th Feb 2016

On 29th Feb I had the pleasure of going to the Findacure Drug Repurposing for Rare Diseases conference which was held at the Royal Institution in London.  My notes on this conference will take up a few posts. This is part 2 of 3. Part 1 is here. Part 3 is here.

The next presentation was by Dr Julie Vallortigara from Ataxia UK. Ataxia UK is a patient led research charity. the charity supports patients with a helpline, magazinr and leaflets, it had a network of people in branches, and arranges patient conferences and workshops. The Ataxia specialist centres are in London, Sheffield and Newcastle. The group raises funds to support a number of projects, specifically;

  • Improving diagnosis
  • Pre-clinical studies
  • Clinical trials
  • Symptom alleviation
There is collaboration between patient groups. pharma companies, clinicians and specialists. The group organised a conference in 2015 which was attended by 43 people from 20 countries. The conference was aimed at sharing knowledge/information/care/treatment and was viewed as a success.

The group are involved with two different drug repurposing projects. Patients with Friedrich's Ataxia, the most common type, have a mutation in the FXN gene which decreases the production of the protein frataxin. The research is testing if the gene can be switched back on to produce more protein. 

The first is for Nicotinamide or Vitamin B3. This has a good safety profile, and a phase 1 trial of 10 people showed promising results, and was reported in the Lancet ( the next stage is a larger trial and the group have been involved with giving the patient voice to the trial design. They are also providing some funding.

The second is for spinocerebellar ataxia type 3 (SCA3), and a range of drugs have been screened using animal models. There were two hits from the process, one of which was the anti-depressant citalopram, which was shown to improve motor function. The researchers are investigating a human trial with the groups help, and the group are also providing some funding,

The group also promotes; introductions to experts, advice on research, collaboration and funding, talks on ataxia and its impact, a patient registry, and recruitment to trials/studies.

Dr Michele Lufino of Oxford University the spoke next, providing an academic perspective on drug repurposing. He has been involved with the drug repurposing for Friedrich's Ataxia (FRDA). Friedrich's Ataxia gives rise to gait abnormalities, with age of onset 5-20. There are effects on vision, hearing and speech, There is no therapy at the moment and so the research is looking at stabilising the symptoms. They are looking at being able to increase the FXN gene in order to do this.

Dr Lufino reported a collaboration between Pfizer, who have a high quality library of small molecules, Oxford who have disease expertise and models, Imperial who are able to run a trial, UCL who have disease expertise and Ataxia UK who have the patients!

The collaboration between these means that there is a smooth and fast transition between identifying a candidate small molecule from the library to being able to run a trial. They are undertaking high quality science.

The speed is possible because  Friedrich's Ataxia is monogenic - it only affects one gene. Also the endpoint is known and there is knowledge on the cause of the disease.

Dr Lufino also mention the Oxford Rare Disease Initiative, ORDI:

Dr Nick Clarke of Pfizer spoke next with an industry perspective. Pfizer are looking to reposition themselves to have a greater involvement with rare diseases. They set up their own Rare Disease Research Unit (RDRU) in 2010, and they have 22 rare disease products on their books. However more recently they set up a Rare Disease Consortium in December 2013 which comprised Pfizer with leading universities, with the aim of making medicines.

They issue a call for projects and have one-to-one meetings with the applicants, this then leads to short expressions of interest, and then business plans.

Their first call was for neuromuscular diseases or haematology within certain disease classifications. This resulted in 400 applications. They were confident on 14 of these. which led to 10 plans, and funding for 5 projects.

Pfizer have around 3 million compounds in their library, and they are keen provide access to this to give compounds for research, and they are looking to collaborate with other companies to expand this number.

The process begins with the small molecule library. These are combined with biologics (genetically engineered proteins) and ideas (from the RDC) and converted into gene therapies (using genes to prevent/treat diseases), which can be turned into a product (medicine).

Some diseases have multiple mutations, and it is likely that products developed using the method would be for specific mutations.

Friday, 15 April 2016

Drug Repurposing Conference, Part 1, London - 29th Feb 2016

On 29th Feb I had the pleasure of going to the Findacure Drug Repurposing for Rare Diseases conference which was held at the Royal Institution in London.  My notes on this conference will take up a few posts. This is part 1 of 3. Part 2 is here. Part 3 is here.

The conference was opened by Dr Rick Thompson, one of the scientific officers at Findacure. He outlined some basic drug re-purposing and rare disease information:

  • Rare diseases affect some 350 million people worldwide, around 5% of the population.
  • Drug re-purposing is taking an existing drug and demonstrating that if effective for a different group of people
When you have an existing drug it has a known safety profile and known side effects. There is a history of human usage and the pathways of action are known. Once an idea for repurposing is identified these factors can reduce the requirements for clinical trials for the new group/population.

When drugs are repurposed there may be changes to the delivery of the drug, the dose of the drug or the formulation of the drug - although new safety data may be required.

Dr David Cavalla of Numedicus and Healx discussed what the opportunities for drug repurposing are.

In summary this process is quicker, cheaper and less risky. He outlined that with conventional drug development for every approved drug that is out there, there is another 23 drugs which have entered pre-clinical trials but not made it that far. The conventional drug development route takes some 4-9 years and costs 1.8 billion, but drug repurposing takes some 1-4 years and costs 0.3 billion.

Some 90% of drugs on the market already have secondary uses, which may be exploiting the same or different mechanisms, and this is an under-exploited area. Computer models can be used to explore if existing drugs have potential other uses.

David gave some well known examples of drug repurposing:

  • Aspirin - 1899: Pain - 1970: Myocardial Infarction and Stroke - 2010: Cancer,
  • Viagra - Originally: Erectile dysfunction - Now: Pulmonary arterial hypertension

The website contains a database of compounds and lists some 94 examples of drug repurposing. The issue is that there is little commercial impetus to explore these avenues.

David described that Healx is working on drug repurposing with patient charities and big data. They are using big data to compare drug profiles with disease profiles to examine for potential matches. They know that some drugs can have some protective effects, and if these protective effects happen to be useful in a different disease there's a potential match.

Matt Hammond presented from a patient perspective. His daughter has congenital hyperinsulinism (CHI), and he told everyone about the emotional rollercoaster he and his family have been on since her birth. He described in detail the unknowns and the uncertainty around the whole journey, which you can read here: One of the conversations he had with a specialist led to the discussion of trialling a drug or removing her pancreas. This is an example of drug repurposing.

Matt gave a very useful list of the hidden costs of rare diseases:

  • Psychological
  • Time (travelling, seeing professionals etc.)
  • Finance (travelling)
  • Missing out (on other activities and events)
  • Form filling (it seems there a lot of forms in some cases)
  • Loneliness (being the only one in your situation)
  • The need to plan everything (because of the effects of the disease) 
This was one of the most useful lists I've seen.

Tuesday, 5 April 2016

Symptoms Timeline

I'd been meaning for a while to get a page together with a symptoms timeline so that I (and anyone else) can monitor what is going on. I've got a spreadsheet which collates information on a monthly basis, which I then aggregate together on an annual basis. It will be another thing which I update annually.

I am tracking more than is shown in the table, but I'm keeping things simple with information which I perceive to be important first. If other information becomes important then I'll add it then.

You can access this here:

7th and 8th April: Minor update to data following me remembering that I'd not put any of my GP appointments in the data. I've also added a second table showing who my appointments have been with. Overall, there is some information on the timeline which I've not mentioned before:

GP Appointments: There are 3 GP appointments now included, although there may be the odd one or two others which I need to track down.

The first GP appointment was in 2008 to get a referral for the genetic testing. I dont remember when I did this, but I have a record of a telephone discussion with the genetics people in Jan 2009 which must put the appointment with the GP towards the tail end of 2008. I've also put in the last part of my first 'phase', the appointment with the neurologist in Bristol, Dr Hardie, who pointed me in the general direction of Pilates.

My other GP appointments are already noted, to get the referral to the National and for the stress/depression clinic, and then the follow up which got me the bladder medication and onto Physio, Orthotics and the bowel people.

The other "new" information is being a bit more explicit in my recollection of my early symptoms, with headline descriptions for the early decades of my life. I've previously mentioned having difficulties sitting cross legged as a child, but it also occurred to me that as a Scout I also found sitting in a canoe uncomfortable for long periods of time.

The observation for the 2000's came from my wife, who I first met right at the beginning of the decade. She observed that when we first went skiing, 2003, I found it easy to be comfortable in the ski boots whereas she (who normally stands with her knees straight) found it quite uncomfortable. So, another subtle observation to go along with my own observation of tripping on flat surfaces - which I had noted walking up and down Epsom High Street in the late 1990's.

All the other observations are described elsewhere in this blog!