Research Program update September 2020

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.

SPG7 research (Sydney)

Gautam Wali

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 in SPG4 cells.

Whilst the Foundation focus has been pushing ahead towards clinical trials with a potential treatment for SPG4 HSP, we never lose 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


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

  2. 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)

    1. 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. 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.

    1. 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.

    1. 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.

  4. If Noscapine is successful in clinical trials, will doctors be able to prescribe this for HSP patients in the US even though it is not FDA approved?

    1. Editor’s Note: The current proposal is for a phase I trial to establish safety and tolerability at the dose levels being tried. If that is successful, a phase IIa study will then look for effectiveness. If there is sufficient evidence of effectiveness, it is the current thinking that a series of phase IIb trials in different countries would be required as a minimum to gain regulatory approval for the drug should those trials also be successful. The FDA would be consulted for their view on the plan for a series of phase IIb trials in order that they would grant approval if successful. So the plan is to have the FDA, the EMA in Europe, the TGA in Australia and perhaps other major regulatory authorities (depending on the countries for the various phase IIb trials) positioned to approve the drug if the trials are successful.

      If for some reason the drug was found to be effective but FDA approval was not forthcoming, you would need to ask people who are authoritative about US regulations specifically on this particular drug and more generally on the issue of prescribing for an unapproved purpose in the US.

    1. Editor’s Note: Before implementation can start, clinical trial plans need to be completed, submitted for assessment of compliance with ethics, regulatory and governance requirements and approval gained. This is projected for completion by the end of the calendar year. The phase 1 trial of safety and tolerability will take 2 – 3 months. The phase 2a trial will run for 6 months. If successful, then a series of phase 2b trials is envisaged for different countries/locations, the duration of which will likely depend more on planning, organising, logistics and funding than on the conduct of the trials themselves.

  5. Dear researchers
    What are the results in mice with noscapine? Is re-myelination seen in mice after giving noscapine?
    And is re-myelination seen in cns axons?
    Did walking or mobility or gait improve?

    1. Editor’s Note: The researchers report that Noscapine has not been tested on mice with HSP as part of their research program. Drug testing for effectiveness in the HSP Research Program was performed in human HSP neural stem cells of different types. In those tests, myelination was not one of the factors examined. This is because significant impairment in nerve myelination in SPG4 is quite rare and likely occurs along with degeneration of the axons.

      The drug testing done with mice in recent studies in the program was not to determine effectiveness. The purpose of that testing was to determine the dose range for the drug most likely to be effective when translated to people with HSP. Levels of a potential HSP biomarker in the blood, brain and spinal cord of the mice were used to define the dose range.

  6. Ok. So some of this is hard to understand. Could this drug possibly reverse the symptoms or even cure HSP? Like, is there a possibility I would walk like a normal person?

    1. Editor’s Note: At this point, nobody knows the answers to your questions, except one – the candidate drug will not cure HSP, that is, it will not correct the faulty genetics associated with the condition. The level of drug effectiveness seen in the clinical trials will need to be significantly slowed disease progression, at least, and remember, the drug is being tested initially only on the SPG4 type of HSP. Better than a result of significantly slowed disease progression would be stopping disease progression. Even better again would be some restoration of impaired function caused by HSP. This might show up in some aspect of walking, balance, muscle strength, reduced spasticity, reduced bladder urgency, reduced fatigue and so on. Theoretically, these things are possible because impaired functions in the affected neurons (nerve cells in the brain and spinal cord) may be returned to near normal in people taking the drug treatment, as they were in the laboratory studies with different types of living human HSP cells.

      However, what the reality is can only be determined by doing the clinical trials. Also, the results are likely to vary somewhat from person to person based on several factors such as disease severity and how long someone has had HSP symptoms. On top of that, there is reason to believe that rehabilitation therapy, which might include gait retraining, strength training, flexibility exercises, balance training and so on, may help maximise the potential benefits from the drug treatment.

  7. Sir trials are started or not? And is it necessary to do exercises? I mean like if we will not do exercises will this medicine work or the ability of the medicine will be decreased? And stationary cycling – will it help in HSP?

    1. Editor’s Note: Documentation of the trials is still not complete, so approval has not yet been gained. This is expected in the next four – six weeks with the phase 1 study starting in the first quarter of 2021. A new research program update will be published in a few days – that will have a full update.
      The effectiveness of the drug is not dependent on exercise, however the benefits from the drug in terms of mobility and functionality may well be maximised with a program of exercise and rehabilitative gait training to correct the musculo-skeletal changes caused by HSP over the years. This will be highly dependent on individual disease status.
      Regarding stationary cycling, potential benefits include increased stamina and overall fitness, perhaps even strengthening weak muscles. However, there is a risk of increasing spasticity. Again, it all depends on the individual – which muscles experience spasticity, which muscles are weak, the peddling action used (e.g. toes down versus heel down)… So all in all, if you can, consult a physiotherapist, get an assessment, get a program of movement and exercise designed specifically for you – and then roll up your sleeves and do it at least every other day.

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