Progress in preclinical studies
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.
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.