International Meeting on Spastic Paraparesis and Ataxias - Overview

Last week I went to the International Meeting on Spastic Paraparesis and Ataxias organised by the Spatax network and the Ataxia Study Group. The meeting was held over 3 days and there is plenty for me to report on, and this topic will be the subject of my next few blog posts. This first post covers my general observations from the meeting, and I'll get onto specifics from the different presentations and posters in later posts.

Full post index:
Overview: http://hspjourney.blogspot.co.uk/2016/06/international-meeting-on-spastic.html
Papers Day 1: http://hspjourney.blogspot.co.uk/2016/07/spatax-meet-papers-day-1.html
Papers Day 2a: http://hspjourney.blogspot.co.uk/2016/07/spatax-meeting-papers-day-2-part-1.html
Papers Day 2b: http://hspjourney.blogspot.co.uk/2016/08/spatax-meeting-papers-day-2-part-2.html
Papers Day 3: http://hspjourney.blogspot.co.uk/2016/08/spatax-meeting-papers-day-3.html
Posters 1: http://hspjourney.blogspot.co.uk/2016/08/spatax-meeting-poster-sessions-part-1.html
Posters 2: http://hspjourney.blogspot.co.uk/2016/09/spatax-meeting-poster-sessions-part-2.html

You can also read the spatax blog with plenty of pictures and details about the presentations and various goings on: https://spatax.wordpress.com/2016/06/22/follow-the-news-on-the-spataxasg-meeting-on-spastic-paraparesis-and-ataxias/

Before I get on to those things, a quick update on my survey to find out peoples thoughts on topics for my 2016 survey. The two clear leading topics are Fatigue and "Finding out information about HSP". I'd welcome any further comments and suggestions here, I am starting to work out my question strategy at the moment: http://www.surveygizmo.com/s3/2798869/88680a3a74e1

Back to Paris - Firstly some thanks are due. Thanks to the HSP support group for covering my expenses. My employer (Atkins: www.atkinsglobal.com) lets staff take 2 days a year leave to support charities, so thanks to them for giving me the time to attend. Thanks (obviously) to my wife for looking after the boys whilst I was out having fun for a few days!

Since I was going to be at the conference I took the decision to submit an abstract for a poster covering my survey results, which was accepted. You can see that on my research page http://hspjourney.blogspot.co.uk/p/my-on-line-resarch.html So, thanks are also due to the people who have answered my surveys the last 3 years. Therefore, I had three topics of conversation with people - My own HSP, the results of my surveys and being part of the UK HSP group. The meeting was attended by over 200 researchers and medical professionals, and I was very pleased to have the results of my surveys up in the room for them all to have a look at. I saw many people looking at it, and I engaged in conversations with a fair few of them!

The meeting was really friendly, and I felt quite at home there. The network of researchers feels really close knit, and I was pleased to see and hear about people chatting with each other and sharing their knowledge and findings. In many respect the coffee breaks, lunches and evening social events are just as important as the presentations as they allow people to go and share ideas.

I spotted that overall there were more posters and presentations on Ataxia than there were on HSP. There was also relatively few posters and presentations on treatment and/or relief of symptoms, although it was acknowledged at the end of a couple of presentations that research on treatments may be more prevalent in the next few years.

All of the presentations (also known as papers) and posters were in English, which I was quite relieved about. It wasnt until sitting there and listening that I realised how lucky I am to be able to think and speak in English, whereas the majority of people there (from 22 countries) and having to think in one language and speak in another. The standard of presentation was high, and language did not seem to be a barrier at all.

There was a wide range of papers presented, in all sorts of fields and I have yet to piece together how all of these wide and varied topics fit into the overall HSP picture. Topics included genetic identification, proteins, bio-markers, animal models, genetic testing, cell biology, diagnostics, muscles, clinical diagnosis, symptom identification, age of onset, disease severity etc. You can probably guess that this is the "agenda" for my next set of blog posts!

I spent some time talking with the people from Euro HSP who are keen for the UK group to join. This is quite the opposite to the EU referendum held in the UK on the first day of the meeting (and reported in the second day) which resulted in the beginning of the UK's EU exit.

I think that the various patient groups need to work together, and not just the HSP groups, but those groups for people with similar conditions - Ataxia, CMT, ALS and others. I'm going to explore this further. I found out that in New Zealand HSP is covered under the group for MS, there is no group for HSP in Turkey. Within Europe the national groups have different focuses, with some focusing on fund raising and other providing support. The ataxia groups I spoke to seem to be very similar to the HSP groups, which makes me think that working together should be easy, and in France this is already done.

Speaking to various people about my 2016 survey, suggested topics include physiotherapy/stretches, bowel issues and anxiety. A few people are also looking to set up surveys of their own in their own countries.

You can see a pic of me here, with my poster - it was the first one up!

A busy weekend - Three conferences

Next weekend is going to be a busy one.

On Sat 24th June is the UK HSP Support Group AGM http://www.hspgroup.org/index.php/meetings/68-agm-leamington-spa, however this is the first year in 4 that I wont be going. Instead, I'm off to the Spatax networks HSP and Ataxia conference in Paris https://spatax.wordpress.com/2015/07/20/next-international-meeting-on-spastic-paraparesis-and-ataxias-june-23-25-2016-paris/, to represent the HSP support group.

This is a combination of several things, my employer, Atkins, offers 2 voluntary days per employee per financial year, and so they are paying for my time to be there. The HSP support group is covering my conference, travel and accommodation costs. I'll simply be reporting back on what I find out.

I looked at the programme for the conference, and they were accepting abstracts for poster sessions. I put an abstract together covering my three on-line surveys which was accepted. So, for the last week or so I've been busy pulling together a poster which summarises the results of the surveys, which will be up for the worlds leading HSP researchers to have a look at.

I'll share the poster here when it is finished!

20th June Update - link to finished poster https://drive.google.com/file/d/0BzEoTkR5HCWhNzllZWZWR05qWk0/view
Note. Some browsers dont seem to like this file, but you should be able to download and view in acrobat v8 or v9.
A larger but more compatible file is here: https://drive.google.com/file/d/0BzEoTkR5HCWhTklWZFNDWGlSYlU/view

If that wasn't enough, there is also a findacure event "How Rare Disease Patient Groups Can Work With Researchers" in the afternoon in London https://www.eventbrite.co.uk/e/how-rare-disease-patient-groups-can-work-with-researchers-workshop-tickets-25054044321

So, thats three interesting and relevant meetings which could be gone to - obviously I've very excited to be going to Paris, sharing my findings and finding out about what else is happening in the world of HSP. I'm hoping to be able to tweet from the conference.

If any readers have any topics they particularly want me to find out about, then post a comment, and I'll do my best to find out.

Collecting Ideas for 2016 Survey

Hello everyone,

I'm starting to think about what to cover in my autumn survey this year. I've got a short survey which I'd welcome anyone to complete if they've got any thoughts.

http://www.surveygizmo.com/s3/2798869/88680a3a74e1

Time-scale wise, I'm getting my thoughts together over the summer to launch in ~September.

AFO - Ankle Foot Orthosis

Some weeks ago I had a joint appointment with my physiotherapist and my orthotist. Conversations with each individually had been questioning if it was right for me to get an AFO (ankle foot orthosis), but also suggesting that I talk to the other specialist. So, the easiest thing was get them both together and discuss this openly.

They both watched me walk and the conclusion was that I am right on the borderline for needing them. My left leg is a bit tighter than my right leg, and we agreed that I would start by getting one AFO for my left foot.

I find that walking is more challenging when one (or more) of the following is/are true:

• Tired
• Stressed
• In a hurry
• With an awkward load
• After a few drinks

Therefore, I'm generally fine in the mornings, but things do deteriorate as the day progresses, especially if several of those points are ticked off. (You can draw your own conclusions about my 4-year and 7-year old "awkward loads", actually it is mainly their baggage rather than them!)

I decided that I would wear the AFO in the evenings (when going out) or when I was expecting to be suffering from several of those points at the same time. The order was placed there and then.

Last week I picked up my own Helix AFO http://www.orthoticcomposites.com/helix-afo/ (left, large).  This is a carbon fibre AFO. Reasons for choosing a carbon fibre one as that I still have lots of power in my muscles and the flexibility in the carbon fibre allows me to use some of that power whilst walking - it allows me to be dynamic, rather than just holding the foot in a fixed position. Having a flat surface means that I can use the AFO in combination with my insole(s). The general advice from my orthotist on collection:

• Build up the use gradually from day-to-day, starting with a couple days at half an hour, then ramping up over a week.
• Stop wearing it if it rubs.
• The weakest point is the join between the foot plate and the strut, so avoid big ankle bends!

I asked how long it would last - she said that someone wearing them full time might expect a couple of years use, but that is dependent on how mobile they are. As I'm only planning to wear mine in the evenings occasionally, I'll speculate ~6 years expectancy.

Yesterday, one of my colleagues retired from work, and there was a celebratory social gathering in town in the evening - a perfect opportunity to try out the AFO. It worked really well, I'm fairly sure that there was less scuffing of my toes as I walked to and from the bus stop/pub. Obviously I need to try this a few more times and see how things develop, but I did feel good not having to worry too much about my feet scuffing. It makes me realise that all those subtle small changes do add up over time. Conclusion - I expect that I'll end up with 2 of these at some point!

Although the AFO is quite discreet, I walked past my barbers on the way to bus stop, and he noticed it through my trousers, but then he has an inch and a half block in one shoe to equal his legs out. No-one said anything when I was in the pub. However, I must trim the strap so that it is a bit less bulky. (My boys are not sure if the AFO now makes me a cyborg or not....) 

p.s. I must apologise to my orthotist - I just went for broke and used the AFO all evening, about 6 hours, without all the gradual use build up - I did a short build up on the day I got them and then no more. 

What does it look like? - Here are some pictures....

With the insole....

In a shoe.....

Re (act) community

April was a busy month, not only did I get the write-up done for the Drug Re-purposing conference, I also found out about more HSP communities, which I describe one of here, the Re(Act) Community: http://react-community.org/diseases/606

This community aims connect researchers and ideas through cooperation and collaboration and promoting scientific projects through crowdfunding. They aim to be a game changer, spreading the voice about the urgency of investing in rare and orphan disease research. They believe that everyone can contribute to support scientific research and the community is open to researchers and to interested patients and other people. I saw this on twitter and spotted quickly that HSP is one of the rare diseases included.

I signed up and became the second follower of HSP. The site needed 15 followers in order to "unlock" HSP, so with a bit of twitter, Facebook and LinkedIn action I found enough interested people to unlock HSP - and thanks to all those who signed up!

Now that HSP is unlocked interested researchers can submit their proposals, and we can test the crowd funding side of the site. 

Readers are welcome to join in and support, as a patient or just as a follower. You will need to:

• Register with the site
• Go to HSP
• Support/follow it

There is no commitment from you to do anything! You can choose to get notifications or not from the site.

If there are any researchers reading, you are also welcome to join in. Researchers are able to submit projects, which are screened by the sites Scientific Advisory Board.

On the crowd funding side of things the website seems only to have one project up and running at the moment, so it is in its early days. People can donate money in if they wish (the site takes 10% of donations to cover costs), and people can donate money to HSP specific projects if they wish.

I note that not only is the umbrella HSP term there, each of the SPG variants is listed separately. This comes because the site gets its list of rare diseases from a database which includes both the umbrella term and the specific SPG variants. I decided to also follow some of the SPG variants, other similar conditions as HSP (including ALS, PLS, CMT, Friedrich's Ataxia) and rare conditions of others I know (including MD, Turners Syndrome, Ehlers Danloss), and some of the more common hearing ones (including Meniere Disease, Alport Syndrome, Vestibular schwannoma).

You can follow the site here:
https://www.facebook.com/REACT.community.official
https://twitter.com/react_community?lang=en-gb
The site is set up and run by:
http://www.blackswanfoundation.ch/

In summary, I was very pleased to be able to get enough people interested in this in order to unlock HSP, and in fact that is now the condition in 4th place, follower wise, on the site, whereas at the beginning of April there was, like many other diseases, just one follower. I'm pleased to have gotten another potential research channel unlocked, but actually getting researchers to get involved might be a bit more of a challenge, though!

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: https://rareomics.healx.io/disease/spastic-paraplegia-hereditary .

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.

Funding

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. http://www.findacure.org.uk/category/news/page/2/ 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!

Summary

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.

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 http://web.mit.edu/iandeseminar/Papers/Spring2006/Demonaco.pdf. 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 https://clinicaltrials.gov/ct2/home

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.

LIGHTNING TALKS

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. http://www.sparks.org.uk/

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. http://www.linguamatics.com/products-services/about-i2e

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.  https://rareomics.healx.io/

PANEL DISCUSSION

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.

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 (http://www.ncbi.nlm.nih.gov/pubmed/24794816). 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: http://www.rarediseases.ox.ac.uk/home

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. http://www.rarediseaseconsortium.co.uk/

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.

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 http://www.drugrepurposing.info/ 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: http://www.diseasespotlight.com/rare-disease-hyperinsulinism/. 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.

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: http://hspjourney.blogspot.co.uk/p/symptoms-timeline.html

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!