HSP clinical trial program update June 2019

Progress in preclinical studies and clinical trial preparation


Rebecca Schüle

Blood biomarker* study (Tübingen, Germany)

A biomarker is a measurable indicator of the status (presence or absence; severity; stage of a disease) of  something that can’t be measured directly. For example, body temperature is a biomarker for fever. Currently there is no measure of the status or rate of progression of most forms of HSP that is sensitive enough for measurements in clinical trials.

A blood biomarker study for SPG4 HSP is underway in Germany with a team led by clinical trial team member Dr. Rebecca Schüle. The Foundation provided over AU$110,000 in funding support in early 2018 to this study. This funding enabled the study, which had already been launched, to double the number of blood samples from people with SPG4 HSP.

The aim of the study is, in preparation for clinical trials, to determine if target compound levels measured in blood samples taken at several time points, increase or not over time and if that increase correlates or not with the clinical progression rate of HSP.


Dr. Schüle reports:

The project began in January 2018. It took until September to establish the assay (test) conditions. Questions we needed to answer included:

  • Does it matter how quickly a blood sample is processed?
  • Can we thaw, refreeze and thaw samples again or does that change the measurements?
  • If we take two blood samples of the same person on the same day, do we get the same results?
  • How stable are the results – do we need to measure samples in duplicate or triplicate?
  • We usually measure 35 samples in duplicate in one run; what if we measure the same samples on a different plate on another day? Does that influence the results?
  • Quanterix produces the analytical kits in ‘batches’. How variable are our results within the same batch of analysis kits? Is variability increased if we use analytical kits from several batches for the project?

This is all part of the process of assay validation. Where it is intended to use an assay in a biomarker study or a clinical trial, achieving validation is one of the bigger challenges of the whole study.


Christian & Elke preparing samples for analysis


The analytical kit that is commercially available for the two target compounds in this study is currently a beta version i.e. technical validation is still ongoing. We therefore performed a cross-validation study with two other labs that are very experienced in biomarker research and use different platforms to measure the target compound. For this study we measured the exact same serum samples in all three labs and then compared the analytical sensitivity across these platforms. The results have recently been accepted for publication in a scientific journal. We hope this will make it easier for other groups to implement assays for the target compound.


Christian programming the Simoa assay analyser


In parallel with the assay validation process, blood samples of people with HSP and people without HSP (controls) were collected. Levels of the two target compounds are considerably dependent on a person’s age. So samples had to be collected from the control group across a broad age spectrum. For the HSP samples, we had already done a pilot study in a genetically mixed group of 96 HSP cases that showed that target compound levels in HSP are elevated compared to controls. So we then decided to focus on genetically proven cases and some common genotypes. 227 samples from 150 HSP cases with common HSP subtypes were selected. Target compound measurements have been done for about two-thirds of the samples. It is hoped to get even more samples from other groups such as the CReATe biobank (USA).

The next steps will be to finish measuring all the samples and then analyze the data. We are particularly interested in whether:

  • target compound levels differ between HSP genotypes
  • biomarker levels correlate with disease severity as measured by the Spastic Paraplegia Rating Scale.


Gautam Wali

Blood biomarker study (Sydney, Australia)


Over the last three months, there has been significant progress in the blood biomarker study led by Dr Gautam Wali. The assay (test) being developed to detect and measure the biomarker in the blood samples of the HSP participants has been optimised and verified – a challenging and vitally important step in ensuring confidence and reliability of the data that will be generated in the study.


Another vitally important step with the same aim has also been successfully completed, namely, ensuring that the healthy, control samples exhibit relatively consistent levels of the biomarker. When these levels are then manipulated by applying a range of concentrations of a compound that is known to affect levels of the biomarker, it has been established that the assay is sufficiently sensitive to detect minor changes. This improves the chances of getting significant and meaningful results from the study.


Looking ahead, further verification of the assay will be undertaken and the SPG4 HSP blood samples will be tested for their levels of the biomarker. The biomarker will also be tested in different fractions of the blood. Depending on those results, decisions will then need to be made about the direction of the study from that point forward.


Foundation President, Frank McKeown

Dose range finding study (Brisbane, Australia)


Inconclusive results a setback


The question “how much Noscapine do people need to take to achieve the target concentration in the brain?” remains unanswered today despite three studies spanning 22months at a cost of AU$186,000 to the Foundation. The results of the dose range finding study in mice that was completed in March show limited evidence of the drug or of an effectiveness biomarker in the brains and spinal cords of the mice. The study report says “strong conclusions could not be drawn due to technical and biological variability”.


These are not the sort of results we in the HSP community are used to over the 10 years of the HSP research program. It is worth mentioning two things, firstly, that the science, the scientists, the processes and technologies employed in these studies are all world-class. The reason to undertake scientific research studies is to find reliable evidence to determine what works and what doesn’t work. Sometimes that answer is not ‘yes’ or ‘no’, but ‘maybe’ as it is in this case – not a result that anyone wants.


Secondly, I find myself reflecting at this point on the reality that there are well-known diseases, including at least one disease similar to HSP, on which tens if not hundreds of millions of dollars have been spent over the past three or four decades trying to understand and find cures for them … largely without success. This scenario is much closer to the norm for medical research than the progress and success we have had in the HSP research program.


By any measure in medical research terms, the progress we have made with the HSP research program on a shoestring budget in a short space of time is nothing short of astounding. At the start, we funded the first HSP gene testing service in Australia that covered three main genes. We then funded a pilot study to see if stem cells from nasal tissue samples of people with HSP were a good way of studying the disease. Six years later the research team had identified potential drug candidates to treat SPG4 HSP, the main form of the condition.


So this latest result is a speed bump – a pretty big one that has slowed us down considerably – but it is not a roadblock. The clinical trial team are now examining the relative merits of different pathways for moving forward from here. As always, we will keep you, the members of the HSP community, informed via the quarterly progress reports.


Alan Mackay-Sim

Smartphone app biomarker study (Brisbane, Australia)


The overall aim of the study is to test the potential for the smartphone app to constitute a biomarker of HSP status and how it changes over time.


A third session of data collection in the smartphone app biomarker study took place at Griffith University in Brisbane in late March. Nine HSP participants each completed three rounds of walking a set course to collect data on their unique movement patterns. This data will be compared against that generated by the same participants in previous sessions, which were held in February and November 2018.

Participants were subsequently interviewed, being asked a set series of questions to get their own observations about their walking performance in general over the period of time since the previous session – had their walking changed noticeably? To what extent and in what ways? They were also asked about differences in their walking performance over the three rounds of the session they had just completed. Their responses will be used to see if there is any connection between their own observations about their walking performance and what is suggested by the data generated by the smartphone app.


smartphone strapped at the waist & video recording data


Additional data analysis will be performed on the data generated in the March session with the aim of identifying real differences in walking performance.


Participants and research staff relax after the session


  1. I am not a native English speaker. And did I understand correctly that you have nothing at all?

    1. Editor: The inconclusive results are from the dose range finding study only. There was a significant amount of new learning gained from the three studies, but they failed to provide the necessary information for a regulatory authority to approve a dose range for a clinical trial.

  2. and what should we expect now? you have not even written your plans, thus taking away hope. just sit for a quarter, bounce your foot?

    1. Editor: Members of the clinical trial team are engaged in a forward planning process. This is a demanding task requiring creativity, detailed examination, consultation and careful consideration of different scenarios and options… Something that should not be rushed.

  3. Thank you soooo much from the bottom of my heart for the work and effort you put in daily to helping towards a cure for HSP.
    Minor setbacks happen, unfortunately… bit I think we are closer than ever.❤

  4. translated: Much encouragement and thank you very much for your work. I just made a donation again. Do not stop researching. You are our hope !!! Thanks from my heart.

    original: Mucho ánimo y muchas gracias por su trabajo. Acabo de hacer un donativo de nuevo. No dejen de investigar. Ustedes son nuestra esperanza!!!. Gracias de corazón.

  5. I have to admit that I agree with Tara- Thank you so much for giving some hope.Especially now that I’ve run out of tears.

  6. Hello, I’m from Barcelona, ​​I’ve been following your great job to find the cure for a long time now. thanks to all those who are working. You, in Australia, are trying to cure with a dose of two drugs.
    But can’t you try to use this new gene editing tool, which says it allows you to cut and paste, called CRISPR / Cas9, improved versions have been released, one of the researchers is called Marc Güell Cargol, from Olot, a city of Catalonia, but they are working in the United States at the University of Harvard.
    I assume that each group of researchers is following its long and specific path.
    Anyway, thank you very much for your work, and to try it, I am convinced that sooner rather than later, you will find a cure.

  7. I have had hsp7 for years and have been using cannabis.

    Small amounts of good cannabis x2 daily. Cannabis helps.

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