Thursday, 25 August 2016

Spatax Meeting - Poster Sessions Part 1

This post covers part of the poster sessions. I've chosen to give a brief summary of posters which I found interesting. I will write another post which goes into some further detail about other posters. Obviously, I'm not going to mention my own poster - thats fully covered here:

Potential HSP treatment - Simvastin
Ylikallio, Auranen, Isohanni, Lonnqvist & Tyynismaa from Helsinki reported new mutations in HSP SPG5A / CYP7B1. This gene is known to encode an enzyme involved in cholesterol metabolism, with patients accumlating 27-OH-Cholesterol. One patient was treated with Simvastin, which reduced the 27-OH-Cholesterol  with no adverse effects.

HSP/ALS Overlap
Denora et al from Inserm, Paris report an overlap with HSP SPG11 and ALS. They report neuropathological overlap and some shared clinical features. This opens up new fields of investigation.

Disease Re-classification
Goizet, Mathis, Tazir, Couratier, Magy & Vallat from France/Algeria describe proposals for re-classifying Ataxias in a more understandable fashion, by mode of inheritance, gross phenotypic and genes/mutations. They also indicate this might be feasible for HSP.

Sobanska et al from Poland report that non-motor nerve tracts are affected in the brains of some patients with HSPs SPG3 and SPG4. They report the potential for finding additional symptoms in such patients with the use of more detailed neurological diagnostic tests. They question if the types of HSP should be divided into "pure" and "complicated" any more.

Balance training
Casali et al from Italy report the investigation of the relationship between trunk and thigh movements for people with Ataxia. They report that the drop in coordination between upper and lower body impairs dynamic balance, and this this should be a target for interventions. They propose the use of elastic suits.

Cakrt et al fom Prague report the use of a Brainport balance device ( with people with ataxia with cerebellar degeneration, and describe an improvement in postural control and 2 weeks of training.

Vavla et al, from Italy report the use of neuroimaging in HSP and Ataxia identifying consistent structural and functional changes which correlate well with disease severity, with the potential for use as biomarkers. 

HSP populations 
Updates/reports on HSP populations around the world were given, with 79 patients from Greece reported as following the patterns of other European populations. 75 patients from Israel have been included in a new database. 746 patients with either Ataxia or HSP are included in a Norwegian database, and 35% of these have a molecular/genetic diagnosis.

Gene Panels
Several reports were given on the use of gene panels for HSP, 243 patients in Italy were tested with one of 2 panels of 126 or 200 genes, finding a match in 22%, and reporting some Ataxia/HSP overlaps. A group of 98 families in Portugal were screened with a panel of 70 genes, finding matches in 21%. A study looking at all 74 known HSP genes couldn't find a match in 36% of 283 HSP patients.

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.

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.

Full post index:
Papers Day 1:
Papers Day 2a:
Papers Day 2b:
Papers Day 3:
Posters 1:
Posters 2:

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