Research Program update December 2020

Clinical trial timeline

SPG4 clinical drug trial

The Research Program update on the clinical trial for December 2020 can be viewed as a video. Read the full report below for more about other parts of the research program.

The graphic below outlines the recent, current and future development of the SPG4 clinical trial program. The process looks deceptively simple at this high level look, but inside each of these boxes on the graphic is an ocean of depth and a mountain of detail.

The current efforts remain focused on the methodical determination and selection of the highest value assessments and measures for use in the phase 2a trial. As with so much of this 10 year+ research program, the scientific work is pioneering and discovery learning, including what different assessments (such as spasticity, strength, balance, various aspects of gait and so on) amongst the numerous possibilities are likely to provide the best guidance in determining drug treatment effectiveness. Assessments will be evaluated individually as well as part of a composite measure. Another important consideration in planning the raft of assessments and measures for the phase 2a trial is the likely impact on participants… how long clinic visits will take and how demanding they will be on people.

The drug manufacture and supply process is complex and is taking longer than expected to identify a suitable supplier. As this can’t be done in Australia, the global pandemic appears to be interrupting and delaying the supply chain. Every dose needs to be identical in every respect across the full range of doses of the active ingredient from zero to a determined maximum. Not only does the company and particular manufacturing site have to be certified to an international standard, but quality testing of the active pharmaceutical ingredient (API) is rigorous throughout the manufacturing process.

Formal documentation (Synopsis and Protocol) is ongoing so it will not take much to finalise once all the necessary upstream decisions are made regarding the choice of assessments and drug supply. Once completed, the documentation is submitted seeking approval to conduct the clinical trial.

Even though the graphic shows the phase 2a trial beginning in the second half of next year, what are called ‘baseline measures’ of participants will get underway as soon as possible in 2021 to assess participants’ HSP status before receiving medication. The reason for this is that treatment effectiveness is an individual assessment for each participant. It is based on the changes that occur for the individual from the start to the end of the trial, so it is necessary to assess HSP status and rate of progression leading into the trial.

Blood biomarker (Sydney)

Dr Gautam Wali

We have developed a test (assay) that can detect the effect of Noscapine treatment on a biomarker compound of microtubule dynamics in blood. Our previous experiments had shown that the effect of noscapine on blood cells (PBMCs) can be detected after 16hrs of in vitro (laboratory dish) treatment. In view of the needs for the upcoming clinical trial, we have now achieved a reduction down to 3 hrs to detect the noscapine treatment effect.

We have been working on further modifying our blood biomarker assay for clinical trial applications. We have tested multiple sample collection protocols and have now identified the optimal option. Initial sample processing involved 12-14 steps and took 2-3 hours for each sample. This has now been refined to a one-step 20-minute process (protocol). This approach increases sample viability and is efficient when processing large numbers of samples making it ideal for clinical trial testing.

We are now work on adapting our assay to a high-throughput assay setting necessary for batch sample analysis. This allows samples to be analysed in a single assay run, avoiding sample-to-sample variation providing more reliable results, and is time and cost-effective. For comparison, when processing samples individually, there can be significant sample-to-sample variation, so each sample would be tested up to 3 times to provide reliability and confidence in the results. In high-throughput batch sample analysis, all samples are analysed simultaneously and analytical process variation between samples is eliminated.

Skin fibroblast biomarker (Sydney)

We are applying a novel machine-learning-guided, high-content microscopy image analysis approach to HSP and control skin fibroblast samples. We are presently analysing data and working towards preparing a manuscript.

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. A machine-learning-guided, high-content microscopy image analysis approach to comparing HSP and healthy (control) skin fibroblast samples is being developed. Analysis of experimental data is continuing and a scientific paper for publication is in preparation. (Dr. Wali also leads this study)

Grant funding applications

Two grant funding applications were submitted in November to the NHMRC for a Phase 2b clinical trial. The lead time for grant funding is such that now is the time to be applying for funding for trials commencing in 2022.


    1. Editor’s Note: Here is an article from May 2020 on the website about a patient registry being set up for SPG11 and SPG15 by the European SPATAX network. There is also an email address listed. I suggest you write and make enquiries of this person. He and a colleague of his published this paper in August 2020: that references SPG11.

      There is a small but steady stream of research on SPG11 being conducted globally. You can keep up to date with publications on SPG11 research at the PubMed website:

  1. What is the news with HSP4 now? What research projects have been carried out? Is there a drug for HSP4? When will the drug be available?

    1. Editor’s Note: The latest on our research program is contained in the article on this webpage. Charting the progress of projects over the past 12 years can be found here: For more general information on SPG4 HSP research, use this search:

      The current objective is to test the candidate drug Noscapine in clinical trials, initially for safety and tolerability at the calculated doses, and if successful, to determine preliminary effectiveness in a follow-up trial. If that is successful, then larger multinational trials will need to be implemented to prove effectiveness and get market approval from regulators for the drug. When that might be is too difficult to estimate at this point.

  2. What kind of injection are you going to use? Can you use a virus vector? What is the injection method? aav carrier?

    HSP4 What other research institutions are there?

    Does any pharmaceutical company study hsp4?

    1. Editor’s Note: From your questions, you may have the impression that this research program is pursuing a gene therapy cure. That is not the case. The aim of this program is a disease-modifying drug treatment.
      A listing of national support groups can be found here: There are numerous universities and institutions globally conducting research on central nervous system diseases, with many of them dedicating significant resources to neurodegeneration, often including HSP. A review of published papers in the Research Highlights archive on our website will give you a good idea of the main people and institutions involved in important HSP research.
      No pharmaceutical company is studying SPG4 type HSP to the best of our knowledge.

  3. I know that many events can affect this process, but if everything went perfectly, could you give a timeframe for completion of the Noscapine clinical trials and availability of this drug for use by HSP patients? The progression of this disease has me hanging on to this clinical trial for hope. When human trials begin, could we get more frequent updates? I did not see openings advertised for phase 1 clinical trial participants. How were these people selected? Will phase 2 use the same participants, or will they need new subjects? I’ve seen that HSP can damage brain cells. Has Noscapine shown improvement of this in mouse trials? As far as you know, does Noscapine improve current disability or only improve further disease progression?

    1. Editor’s Note: Planning ahead in this clinical trial can only go so far, given so many unknown variables. This will be the first drug trial in SPG4 HSP. The candidate drug has never been used in the dose ranges envisaged for trialling. Drug supply for the trial has still not been secured due to global pandemic supply chain interruption. The current plan that covers both phase 1 and 2a is under review for feasibility given the circumstances. There needs to be success in each phase and success in each phase will inform the design of the subsequent one. Phase 1 is hopefully somewhat predictable in that it should take less than three months to complete, but without drug supply, a starting date can’t be set. Phase 1 will be implemented by a contract research organisation with healthy participants, so there has been no advertising for participants. Phase 2a will be conducted with people who have confirmed cases of SPG4. In this, as in many things in life, there is the choice of ‘false certainty’ or ‘real uncertainty’ – meaning that any timeframe for completion of the clinical trials and when the drug might be available for use is just a guess – there are way too many variables with unknown outcomes, each and any of which will affect the timeframe. As it is there are many like yourself with hopes for this clinical trial, but “hanging on” the timeframe for an outcome, let alone the outcome itself, may not serve you well in either the shorter or longer term.
      Noscapine has not been trialed with HSP mice in this program. The evidence for improvement in impaired functions is in different types of human HSP cells from people with SPG4 HSP – neuronal stem cells from nasal tissue; induced pluripotent stem cells; and neuron-like induced pluripotent stem cells. No one knows the answer to your last question. The clinical trial is designed to learn the extent of slowing or cessation of disease progression or, hopefully, improvement.

Your email address will not be published. Required fields are marked *