Research program update June 2022

Finding a pathway forward

SPG4 clinical trial

You may remember in previous research updates we talked about roadblocks to moving forward with the clinical drug trial for SPG4. With the expectation that the roadblock due to the COVID pandemic is not permanent, the main impediment to progress is financial, both directly and indirectly. With the sticker price of a phase 1 clinical trial tripling over earlier estimates, the ‘risk’ profile of the initiative shifted substantially. The level and quality of evidence required to proceed to clinical trial also went up commensurately. It is time in the Foundation’s development to have a Scientific Advisory Board (SAB) or equivalent function, independent of the Foundation to advise and guide on investing research funding.

Although a step in the right direction, an SAB is not the perfect vehicle to be making decisions about proceeding to clinical trial. It is a different context with different questions to address than when deciding on the merits of one or more research projects. Neuromuscular diseases NMD as a group came together some years ago and created TACT (Treat-NMD Advisory Committee for Therapeutics):

“Established in 2009, the TREAT-NMD Advisory Committee for Therapeutics (TACT) is a unique multi-disciplinary international group of internationally recognized academic and industry drug development experts as well as representatives of patient foundations and regulatory experts, who meet twice a year to review and provide guidance on the translation and development path of therapeutics programs in rare neuromuscular diseases.”

They are effective and have an excellent track record, with the development of treatments and cures in recent years for Spinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD).

Neurodegenerative diseases NDD, a group that includes the HSPs, could do the same, coming together as a group, with one of the purposes being to establish an advisory committee for therapeutics, as TREAT-NMD have done so successfully.

The Foundation is actively moving forward to get the help that we need in this regard.

SPG7 research

Gautam Wali

The SPG7 induced pluripotent stem cell (iPSC) project, funded by the SP Foundation (USA), using both olfactory stem cells and iPSC-derived neurons is progressing well. Work is ongoing to more precisely understand the disease mechanism, paving the way for drug discovery. This is the same pathway that was taken with the SPG4 research program that investigated the disease mechanism and produced drug candidates.

Blood biomarker to test Noscapine delivery and action

Over the past year Dr Wali and the team at Kolling Institute (U of Syd) have shown a novel application of a high-throughput assay to measure a pharmacodynamic biomarker using nanomolar protein concentrations appropriate for clinical trials. They have successfully shown the effectiveness of this biomarker in a) brains of mice dosed with noscapine, and b) human blood cells treated with Noscapine in the laboratory dish (in-vitro). This work demonstrates a potential biomarker for the delivery and action of Noscapine in individuals in a clinical trial. This work is now submitted to a scientific journal for review.  

Further biomarker development opportunity

The blood biomarker that can identify Noscapine induced biological changes in human blood cells has already been successfully developed and validated as a high throughput assay by Dr Wali, as reported previously This could be described as being at the ‘input’ end of a clinical trial, however at the ‘output’ end, measures of drug treatment effectiveness showing up as improved clinical outcomes e.g. improved mobility, reduced spasticity and so on, could be more precise than the clinical measures currently available.

There is now the opportunity to test the blood biomarker as a measure of HSP disease severity, progression and, potentially, improvement in HSP status as a result of treatment in a clinical trial for SPG4. To do so requires a study with a large sample size with the potential to give definitive results. Suitable human blood samples in sufficient numbers exist in an international biobank, however they are both in limited supply and expensive to make, requiring a convincing application to the biobank for them to be shared for such a study. That process is in progress. Success will give confidence for conducting clinical drug trials for SPG4 a significant boost.


  1. I am happy to be part of your SPG4 trial. I have a long family history of HSP, specifically SPG4.

    1. Editor’s Note: Thank you Tara. When the time comes, there will be blanket communications about the trial, who is eligible, how to register interest and so on. You won’t miss it!

  2. The research is sounding positive for the moment great we all needed to hear there was an update ,we all will be waiting to see how the Mice go, and the next stage in your Research goes.
    And yes I forgot to Mention Dr Wali’s work great with Noscapine if you need someone to try the drug I am ready thanks.

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