Preclinical studies address the big questions
How much of the drug needs to be taken orally for the right concentration to finish up in the neurons in the brain?
How much is lost in processing along the way?
How would we know if the drug is effective or not?
How would we measure that?
These are the big questions that need to be answered before the relatively straightforward task of giving pills to HSPers in a clinical trial.
Drug dose modelling study
In the last update, we shared with you details of this a computer-based drug dose modelling study to learn more about various factors that affect the calculation of dose needed to achieve target levels with HSPers in clinical trials. That study has recently been completed. The findings of that study are most informative and indicate the need to now undertake an animal study to measure drug concentrations in the blood, brain and spinal cord at different dosage levels.
Measuring HSP status and how that changes over time is not an exact science – at least, not at this point. Regulatory approval for drug treatments, not to mention accepted scientific standards, demand that valid and effective ways be developed to be able to tell, scientifically and definitively, the extent to which a drug treatment is effective. This is not such a big challenge if there is significant improvement, but what if there is slow improvement, or the drug halts further progression… how would we know that? There would be a risk of rejecting a treatment as ineffective when it indeed may be effective.
Here is a summary of the preclinical studies related to the HSP clinical trial:
Studies about the drug itself
Drug dose modelling study – completed mid-October 2017 at a cost of around $50,000.
Dose study in mice – costings are being finalised, expected to be around $80,000. The Foundation Committee will review the proposal for funding approval in December. This is a short study with results expected in the first part of the New Year.
Studies about measuring the effect of the drug (biomarkers)
Brain imaging study in HSPers – planning is well advanced for this study to determine if a particular type of brain imaging is sufficiently accurate and sensitive to be used as a measure of HSP progression/improvement, and therefore be a good reflection of drug effectiveness. Preliminary costings are around $65,000, however may well be higher depending on final participant numbers.
Blood and spinal fluid analysis studies – degeneration of the axons of neurons is associated with various compounds showing up in the blood and spinal fluid. This has never been studied in HSP so far, and may prove to be a valid measure of HSP progression/improvement. One study of blood in spinal fluid is fully planned and costed and ready for implementation. The Foundation is being asked for partial funding for this study of around $115,000. The Foundation Committee will decide on the application for funding in December. A second study is looking at a different compound in the blood that is related to microtubule function. A pilot study is currently underway to determine the effectiveness of a test to detect and measure this compound in the blood.
Gait and movement study – at the end of the day, the effectiveness of any treatment needs to be gauged in terms of improvement in gait and mobility for HSPers, or at least in significantly slowing down or stopping the decline in gait and mobility that happens with HSP. This study is employing a novel approach to quantifying and characterising an individual HSPer’s mobility, including its potential to be a good measure of improvement, of things staying the same or of a decline. Planning for this study is finalised and the development of custom software is in progress. The Foundation has approved initial funding of $5,000 for software development.