Friday, 19 August 2016

Spatax Meeting - Papers, Day 3

This is the fourth and final instalment of the papers presented, this time the third day. As previously, the papers were a mix of HSP and Ataxia papers, and I focused on paying most attention to the HSP papers.

The first of the sessions was on functional studies, with more focus on HSP than Ataxia. 

Evan Reid ( talked about discovering some unifying mechanisms within HSP. He noted that that there are more than 50 genes affected by HSP, but there are a few common themes across these different genes, including cell membrane traffic. Evan noted that Spastin (the protein produced by the Spast gene, and affected by SPG4) has two different forms (or isoforms). There is some redundancy between these forms, but both need to be affected for HSP to show.

Tim Newton ( talked about age of onset for HSP, noting that the HSP's with point mutations tend to have later onset than those with deletion mutations. He also reported that the effects of HSP were bigger when the deletions were larger, particularly if the deletion extended to the next gene along.

The second session focused on diagnostics.

Stefania Magri ( gave an overview of next generation sequencing (NGS) panels, noting the potential for mis-diagnosis, given that there are some overlaps between HSP and Ataxia, with the genetic test giving the opposite result to a clinical diagnosis in some cases. A joint HSP/Ataxia panel was suggested.

Sara Morais ( said that 40-60% of  families have unknown diagnoses. They checked 98 families against the most frequent HSP genes and identified the gene in 21 of these.

Lydie Burglen ( reported similar information about testing for ataxias, indicating that a gene panel would only cover about 20% of diagnoses. 

As before, I realise that it is on a very different level to my normal posts. I know I've just used a lot of terms that I dont normally use, and I've just kept this post to the points which I perceived to be most important.

My key takeaway points from this session are:
  • Gene panels - with the panels of the common genes still only covering some 20% of the tests, that leaves some 80% without a clear diagnosis. I perceive this to be important - particularly letting people know the likelihood of a match, and defining a process after this.
  • The genetic mutations for HSP (and Ataxia) can vary in size, and potentially affect more than one gene, with potentially more than one consequence. 

The question which came through my mind at this time was: how do the dominant transmission cases start - its fair enough to note that they transmit from one generation to the next, but they must start somewhere.

Thursday, 4 August 2016

Spatax Meeting - Papers, Day 2, part 2

This is the third instalment of the papers presented, this time the afternoon of the second day. As previously, the papers were a mix of HSP and Ataxia papers, and I focused on paying most attention to the HSP papers.

The first of the afternoon sessions focused on therapeutic approaches, although all of the papers had an Ataxia spin.

Helene Puccio ( described using computer gait analysis, and using it to investigate gene therapy in mice. One of the aspects they have been looking at is what happens if treatments are given after symptoms are showing - they conclude that if the treatment is given before the death of the neurons then it works.

Eleonora Di Gregorio ( talked about speech communication problems affecting quality of life - The symptom is dysarthria - and this occurs in some HSP's too.

The second of the afternoon sessions focused on therapeutic approaches with biomarkers, and again, most of the papers had an Ataxia spin.

Thorsten Schmidt ( talked about some work involving re-purposing existing drugs for SCA3, and gave 2 examples - Riluzole and Citalopram, both of which were tested on mice - Riluzole was not found to give any benefits and Citalopram was. They are trying to get Citalopram into pre-clinical trials.

Benjamin Cravatt ( similarly talked about drug re-purposing for HSP. He began by describing that some cell pathways for the spread of disease are known, but many are not. They are looking at potentially re purposing diabetes drugs for HSP.

In the discussions at the end of the session it was commented that patient numbers for studies are generally low, and there would be some benefit from regional/continental/worldwide patient registries. As there are overlaps between HSP and Ataxia it is good for the researchers to work together.

As before, I realise that it is on a very different level to my normal posts. I know I've just used a lot of terms that I dont normally use, and I've just kept this post to the points which I perceived to be most important.

Key takeaway points are:
  • Treatments are unlikely to be effective if given after the death of neurons.
  • Some are looking at drug re-purposing for HSP/Ataxia at the moment
  • Several Ataxia symptoms and the way they feature are similar to HSP
  • Researchers are looking for bigger/better patient registries

Thursday, 28 July 2016

Spatax Meeting - Papers, Day 2, part 1

This is the second instalment of the papers presented, this time the morning of the second day. As per day 1, the papers were a mix of HSP and Ataxia papers, and I focused on paying most attention to the HSP papers.

Day 2 was opened by Peter Bauer Peter talked about genetic sequencing and genetic testing using gene panels (i.e. a sample from a patient is tested against multiple specific genes for a match). He outlined that there are three main areas for problems in getting a genetic test, obtaining the sample, doing the preparation for sequencing, and in the interpretation of the results. The perfect genetic test would know about all possible variants and test for repeat expansions. There are guidelines for diagnostic testing: Asking predictive questions of tests can be tough when there is only limited data available - results can be ambiguous. There can be diagnostic gaps in the data - which would miss patients out who would otherwise get a diagnosis. Another issue is that such a test can show "incidental" findings - i.e. a gene is matched which was not part of the original search remit - consent is needed from the patient to find an report these findings. Peter indicated that 5-10% of rare disease patients have two different conditions. He also indicated that it would be a good idea for the Spatax network to work with the UK 100,000 genome project

There were a couple of people - Tzoulis Charalampos and Robert Roxburgh who talked about higher incidences of varying conditions in certain areas - Western Norway and Maori / Pacific Islands respectively - due to population bottlenecks in the past, also known as founder effects. Robert was talking about Canvas Syndrome - a type of Ataxia - noting that a chronic cough can be a symptom.

Rebecca Schule gave a really good overview of HSP. She indicated that the recessive HSP's have an age of onset around 1 decade earlier than the dominant types, and that there is some influence on the age of onset with the mutation type for certain HSP's. When looking at the severity of HSP, this is partially explained by the disease duration, but that only accounts for 10% of the range of severity. They have looked at how the Spastic Paraplegia Rating Scale varies with type of HSP in order to look at rate of change. They found that SPG4 progresses relatively slowly, with a change of 0.38 points per year, whereas SPG5 is faster at 0.74 points per year. You can find details here:  However, she noted that there are a load of factors which affect patients which are not assessed in the SPRS. For example, with a family there may be differences with the same mutation - perhaps a 30 year difference in the age of onset. One of the key questions is deciding when the disease starts. Another important factor is that day-to-day changes in mobility and other symptoms can be greater than the progression of the disease over a few years. There are lots of unknowns. New tools include biomarkers, gait paradigms and video gait analysis. SPG4 is a good candidate for looking at the effects of genetics and environment to understand more about the variation.

As last time, I realise that it is on a very different level to my normal posts. I know I've just used a lot of terms that I dont normally use, and I've just kept this post to the points which I perceived to be most important.

Key takeaway points are:

  • Genetic test results can be ambiguous.
  • Changes in health can be indicators of underlying problems - e.g. the chronic cough
  • Day-to-day variation can be bigger than year-to-year progression

Sunday, 24 July 2016

Spatax Meeting - Papers, Day 1

I had wondered how to present my observations from the conference, and my decision was to present by topic, chronologically - so this post covers the papers presented on the first day. The papers were a mix of HSP and Ataxia papers, and I focused on paying most attention to the HSP papers.

The meeting was opened - Henry Wahlig (of the Tom Wahlig Foundation) indicated that the foundation is awarding a scholarship of €120,000 over 3 years for scientists who are opening up new therapies or treatments into HSP. Further info here:

The first speaker was Harry Orr Harry talked about SCA1 (Spinocerebellar ataxia type 1), noting that the longer the delay in treatment the less able cells are to recover function.  Harry also noted a course in molecular degeneration in 2017 near Cambridge

 Andrea Burgo talked about SPG4, noting that SPG4 accounts for up to 50% of the dominant cases of HSP and up to 15% of the sporadic cases. He observed that the stability and viability of neurons depends on intracellular transport, and that axonal swelling is often associated with axonal transport defects,

Harald Stenmark indicated that SPG10 may no longer be considered an SPG.

Julien Branchu reported on research undertaken in SPG11. They are developing a mouse model of SPG11. This model is a "knockout" model, where the gene is made inactive. They observed that the mice developed gait problems similarly to patients, and they also had cognitive/brain and spinal cord impairments, which are also characteristic of SPG11. The model will allow them to understand more about the condition.

As I write this I realise that it is on a very different level to my normal posts. I know I've just used a lot of terms that I dont normally use, and I've just kept this post to the points which I perceived to be most important.

Key Takeaway points;

  • The longer the delay in treatment the less effective it is
  • Animal models can greatly help the understanding of diseases

One of the terms that cropped up a lot was Purkinje cells - thse are cells that in the cerebellum which are used in processes of motor control and learning. The cerebellum is the part of the brain which has plays an important role coordinating and regulating muscle activity It is more difficult to find an accesible description of the Purkinje cells

Thursday, 30 June 2016

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.

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:

Back to Paris - Firstly some thanks are due. Thanks to the HSP support group for covering my expenses. My employer (Atkins: 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 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!

Thursday, 16 June 2016

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, 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, 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
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:

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

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.

Friday, 27 May 2016

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.

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

Saturday, 21 May 2016

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 (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.....

Saturday, 7 May 2016

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:

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:
The site is set up and run by:

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!

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.