Research Program update September 2020

Posted - September 2020 in HSPRF News

Clinical trial in advanced planning stage

SPG4 Clinical drug trial

COVID restrictions have hampered some research, with the biomarker studies being most affected. However, planning for clinical trials has been able to continue and is well advanced. The planning currently underway includes:

  1. Grant funding applications – identifying and assessing grant funding opportunities; developing and submitting applications.
  2. Finalising the documentation for the trial with an initial two-part plan:
    • Phase 1 determines safety and tolerability of the drug at the doses being tested.
    • Phase 2a determines if the drug works in a 6-month trial with SPG4 HSP participants.
    • When finalised, the documentation has to be submitted for ethics, regulatory and governance approvals.
  3. Getting quotes for implementing Phase 1 from organisations that specialise in clinical trials.
  4. Assess options for the manufacture of the drug treatments for Phases 1 & 2a.
  5. Site Feasibility Assessment for Phase 2a to ensure that the right people with the right resources, technologies and funding are available for the successful implementation of the 6-month trial with SPG4 HSP participants.


Gautam Wali

Gautam Wali

SPG7 research (Sydney)

Meanwhile, important research on the SPG7 form of HSP has recently been published by members of the HSP Research Program team, from a study funded by the Spastic Paraplegia Foundation (USA) and this Foundation. The published paper reports that mitochondria are dysfunctional in SPG7 but not SPG4 cells.

Whilst the Foundation focus has been pushing ahead towards clinical trials with a potential treatment for SPG4 HSP, we have never lost sight of the need for treatments for all forms of HSP. The HSP Research Program team is actively engaged in research on SPG7, following a similar pathway to the SPG4 research. They are now evaluating olfactory stem cells developed from tissue samples taken from people with SPG7 mutations to understand cell functions and mechanisms that are impaired in this HSP type. This understanding will be used to screen for potential drug treatment candidates in the future. The team has received new grant research funding from the Spastic Paraplegia Foundation (USA) to further pursue this work over the next two years.

Blood biomarker (Sydney)

The blood biomarker assay was initially developed to measure the differences between biomarker levels in people with HSP and non-HSP individuals. We now intend to use this assay to measure the biomarker levels in people with HSP pre and post treatment in the Phase 1/2a clinical trials being planned. However, this requires significant redesign of the assaying process with the time between sampling, processing and analysis now narrow, critical and requiring precision, where previously samples could be stored for weeks and analysed when logistically convenient. The assay redesign is presently underway and planned for completion in the September quarter. (Dr. Wali also leads this study)

Skin fibroblast biomarker (Sydney)

Using skin fibroblasts (skin cells grown from a skin tissue sample), the aim is to develop a biomarker to aid in HSP diagnosis and drug testing. For this, we are applying a novel machine-learning-guided, high-content microscopy image analysis approach to HSP and control skin fibroblast samples. The experimental phase has been completed and data is now being analysed. (Dr. Wali also leads this study)

Smartphone app (Brisbane)

Testing session in the new Engineering Building, Nathan Campus, Griffith University

The 4th and final round of testing in the smartphone app study at Griffith University in Brisbane took place in mid-August, having been rescheduled from March due to COVID restrictions. 6 of the 9 regular HSP participants in the study once again took part, with 3 unavailable.

The study seeks to establish the smartphone app as a reliable and valid source of regular data on changes in the mobility of HSP participants that might occur over time as a response to drug treatment in the clinical trial.

Now that all the data is collected from the study, the challenge is to analyse and make sense of it. A new, additional member of the Griffith University Electronic Engineering team that has been working on this study will take on the huge task of data analysis as the topic of a Masters degree. Our sincere thanks to the whole engineering team who have generously volunteered both their time and expertise to this initiative.

Participants in the Smartphone app study taking a break between rounds of testing

Comments on this story

  1. Suzie posted at 9:51 pm on 2 September 2020Reply

    Thanks for this information and all the candidates willing to be in the trials. The more we know the better! 🙂

  2. Louise posted at 6:01 am on 3 September 2020Reply

    thank you for all your work. this gives us a lot of hope. will this medication be suitable for young children? Louise, french mother of two HSP children (SPAST gene)

    • Editor posted at 10:26 am on 9 September 2020Reply

      Editor’s Note: You ask “Will this medication be suitable for young children?” If the drug is found to be effective in adults, then it may well also be effective in children, however it will take further investigation to establish that effectiveness. Dosing differences between adults and children are complex, as it’s not just a linear kg/mg dosing translation. Calculating appropriate dosing for children and adolescents needs to take into account developmental biology i.e. the potential long term effects of a therapy on organs that are yet fully developed. This is especially true for a neurological therapy. There is also a ‘body size’ effect to consider that is independent of weight differences. Because of society’s general sensitivities to the causing of potential harm to children, adult trials are normally conducted first for conditions that affect both adults and children. Given this reality, the question takes on the dimensions of a separate trial in its own right with similar logistics, resource requirements and costs as for the current study. Paediatric studies would likely be done separately after the toxicity picture in adults is well established.

  3. JOSEP posted at 11:51 pm on 8 September 2020Reply

    Phase 2a determines if the drug works in a 6-month trial with SPG4 HSP participants.
    What dose is intended to be applied to the participants with SPG4 HSP? is it noscapine? What dose and time of taking are used?
    Thanks for continuing to investigate and with the advances we can obtain a solution, a cure, or stop the degenerative progress.
    A greeting from Barcelona.

    (Original comment) La fase 2a determina si el medicamento funciona en una prueba de 6 meses con participantes de SPG4 HSP.
    Que dosis se pretende aplicar a los participantes de SPG4 HSP, se trata de la noscapina? Que dosis y tiempo de toma se usan?
    Gracias por seguir investigando y con los avances podemos obtener alguna solución, curación, o detener el progreso degenerativo.
    Un saludo desde Barcelona.

    • Editor posted at 10:37 am on 9 September 2020Reply

      Editor’s Note: The dose range, frequency and timing of Noscapine for participants in the Phase 2a trial is a decision that hinges on the outcomes of the Phase 1 study of safety and tolerability. However when that decision is made, the information will not be available due to trial design and ethics requirements and potential intellectual property considerations.

  4. Barbara posted at 12:53 am on 10 September 2020Reply

    How many types of HSP are there now?

    • Editor posted at 11:24 am on 10 September 2020Reply

      Editor’s Note: There are about 90 forms of HSP found so far. Here is a reference.

  5. Ashraf posted at 6:13 pm on 10 September 2020Reply

    How do I know which type of hsp I have ????

    • Editor posted at 8:21 pm on 10 September 2020Reply

      Editor’s Note: How to definitely know what type of HSP anyone has is through genetic testing that returns a positive result. If a family member has already been tested and a positive result found, then other family members, even distant blood relatives, can be screened for that particular HSP type. A negative result from genetic testing for HSP does not mean that someone does not have the condition, however it makes it impossible to definitely say which particular HSP type it might be. 40% of all genetic testing of people who almost certainly have HSP returns a negative result. This is a reflection of the state of knowledge, development and technology in genetic testing, which is immeasurably better than it was just a few years ago, but still far from foolproof or perfect as a diagnostic tool.

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