HSP research program update December 2019

Posted - December 2019 in HSPRF News

Progress in preclinical studies

 

RA Ernadhi Liyanage, Dr. Gautam Wali, Dr. Sue-Faye Siow

Blood biomarker study (Sydney, Australia)

In the previous update, the use of two different types of blood samples from two groups, those with SPG4 type HSP and matching ‘healthy controls’, was outlined.

Sample type I: The assay (test) of blood from SPG4 and ‘healthy control’ groups has shown that the candidate biomarker clearly identifies one group from the other. Blood from an SPG7 group has also been compared and shows that the biomarker is more highly specific to the SPG4 group.

Sample type 2: In the ‘healthy control’ group, it has been found that the biomarker can be identified in different fractions (components) of blood samples and, further, that the level of biomarker detected varied in the different fractions. The overall aim is to discover the blood fraction with the highest biomarker levels so that differences found in future when the biomarker is being used in testing are demonstrated as clearly as possible. During the most recent quarter, testing of a small number of ‘healthy controls’ has shown that one of the blood fractions being evaluated has levels of the biomarker around 4 times higher than the other fractions. This is great news as it holds the promise of being able to detect tiny changes in the minute amounts of the biomarker found in the blood of people with SPG4 who will be receiving medication during the proposed clinical trial. The next step is to try to replicate these results across all the samples in both the SPAST and control groups.

Analytical methods: Work has now begun on developing analytical methods using the latest technology to more precisely detect and measure the minute amounts of the biomarker compound found. Collaboration has commenced with a specialist analytical team in Brisbane and will be ongoing to develop and refine the biomarker assay. Cell samples have been sent to the group in Brisbane and they will be analysed in the coming months.

Looking further ahead, having demonstrated these differences in a small number of cases, and now pursuing development and refinement of the biomarker assay, there will be a need to validate it in much larger groups of people with SPG4 HSP and matched ‘healthy controls’ in order for it to become an accepted standard suitable for a clinical trial.

 

 

Alan Mackay-Sim

Drug dose range-finding – new study (Brisbane, Australia)

The overall aim is to establish, in a living animal, the oral dose of the drug that is needed to achieve the ideal level in the corticospinal neurons of the brain. The ideal level was established in the earlier stem cell studies using nasal tissue from people with SPG4. The new study is investigating a recalculated drug dose range in a smaller scale test using three dosing levels across 12 laboratory mice.

 

The animal part of the study was completed in the third week of November at TetraQ in Brisbane with blood, brain and spinal cord samples taken and prepared for analysis. Samples will initially be analysed by TetraQ for residual levels of the drug. Following that, identical samples will be analysed at QIMR in Brisbane using test methodology that they invented and developed to detect levels of the potential biomarker being worked on by the biomarker study group in Sydney.

 

Analyses of both residual drug levels and the biomarker are expected to be completed and study reports available before the next update in early March. The pathway forward to a clinical trial is dependent on the findings of this study.

 

Smartphone app biomarker study (Brisbane, Australia)

Discussion and planning of sophisticated modelling and analysis of the data sets generated so far from walking trials with HSP participants is continuing with an expert in Europe.

 

 

 

 

Comments on this story

  1. Jill posted at 3:34 pm on 3 December 2019Reply

    Like many I was greatly encouraged by the reports of Noscapine and its role in relieving symptoms of HSP. I want to pass on my experience so far. I first took Noscapine a year ago, was 10 days in on one capsule per day when I started to feel unwell – ‘unwell’ being diarrhoea and lethargy. I am normally energetic and in good spirits apart from leg weakness and spasticity (hspg7) but took a dive from that day on. The diarrhoea was bad, but no surprise as my digestive system acts up this way on many occasions. I discontinued taking Noscapine but it took at least a month before I was at all well.

    A year later I thought I would try again, bought a new packet, and proceeded cautiously – ¼ capsule two days apart. I am ill again, but recovering.

    Of course, I won’t try again and write this as a warning to others. I’d also be very appreciative of advice or other expert insight. My gp has no experience with Noscapine and can’t help in this regard.

    Jill

    • Editor posted at 4:06 pm on 3 December 2019Reply

      Editor’s Note: The side-effects you describe are known to occur in some cases with this drug. As this drug has been approved for human usage for around 40 years, it has been shown to be very safe, with the side-effects well known – and manageable in most cases.

      The focus of the research to date has been on SPG4 type HSP in stem cells. Its effectiveness with SPG7 is not known. What is known is that there are differences in the respective mechanisms associated with these two HSP types, and therefore questionable likelihood of the drug’s effectiveness with SPG7.

      The overarching questions that can only be answered in a clinical trial are:
      * Is the drug sufficiently effective in treating SPG4 (and perhaps other types of) HSP?
      * If so, what is the ideal dose? and
      * Is there any change in the side-effects experienced at this dose level and/or duration for which it is taken?

      Currently the information about this drug with HSP in humans is individual and anecdotal, so while various effects might be experienced by an individual, there is insufficient data to generalise. Solid evidence that meets the standards of both good science and the requirements of the regulatory authorities can be established only by clinical trial.

  2. Milind posted at 1:57 am on 4 December 2019Reply

    Even I have taken noscapine for more than
    A year it does not improve anything
    Now I am taking riluzole atleast it can
    Protect nerves in spinalcord
    And what is going on I cannot understand
    Still the clinical trials are not started
    As per last data it was told it will Start in 2018 then 2019 and now we have almost came in 2020 we are losing our hopes

  3. Lingarajne posted at 2:55 pm on 8 December 2019Reply

    I am a Doctor myself suffering from BICD2 gene type hsp. I have been taking noscapine for 2 years, it has helped by stopping progression, spasticity has little decreased, no fasciculations but urinary symptoms have not shown improvement. I am taking 300 mg per day.

  4. k posted at 8:21 pm on 14 December 2019Reply

    Hi, everyone. I am a patient with hsp4 from China. I have not taken any medicine for many years, and it is getting more and more difficult now.

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