Progress in preclinical studies and clinical trial preparation
Blood based biomarker study
16 HSPers with SPG4 type HSP have now given blood samples at the Royal North Shore Hospital Neurogenetics clinic in Sydney in this biomarker study, up from 10 over the last three months.
They have also been assessed on the Spastic Paraplegia Rating Scale that covers walking stamina, speed and quality; agility and speed going up and down stairs; ability in standing from a sitting position; measures of spasticity and muscle weakness, pain, bladder and bowel function; and recording of any other HSP related symptoms.
For comparison, blood samples have also been collected from 6 people who don’t have HSP.
The aim of the current part of the study is to develop a test (assay) for the blood samples that is relatively easy to use and generates reproducible results.
The team is evaluating multiple techniques for measuring levels of the blood biomarker that meet these requirements.
Over the next three months an initial batch of samples comprising 15 from HSPers and 15 from non-HSPers will be evaluated.
Smartphone app biomarker study
Following the analysis of data from the second round of testing in November 2018, the research engineering team at Griffith University met with HSP research program principal investigator Prof Alan Mackay-Sim in February to discuss the results and assess the prospects of continuing the study.
The consensus was that promising differences were being seen in the data and that a third round of testing was warranted.
This is expected to happen towards the end of March when the volunteer HSPers for this study will reconvene at Griffith University in Brisbane.
Dose modelling study
The Precision & Systems Biomedicine Laboratory at QIMR Berghofer Medical Research Institute, Brisbane, is in the process of measuring minute changes in a target protein in mouse tissue samples.
The mice were given various doses of the candidate drug for clinical trials, noscapine, in a dose-escalation study.
Changes in levels of the target protein were found to reflect effectiveness of the drug in earlier HSP stem cell studies.
A method had to be created and developed to measure levels of the target protein extracted from spinal cord and brain samples of the mice.
The test (assay) uses advanced mass spectrometers to measure the minute changes at a particular region of the target protein that is affected by noscapine.
The aim of the dose escalation study is to determine the effectiveness of various noscapine dosing regimes. This information will guide decision-making on a regime to be taken into the proposed clinical trial.
The results of the study are expected to be available in mid-March.
Clinical Trial preparation
Grant funding: the pending application for $1.5 million funding for the clinical trial from the Medical Research Future Fund over three years was unsuccessful.
New opportunities to apply for funding are continually being sought and assessed.
Planning: A major planning activity was conducted in late December in conjunction with our external clinical trials consultant.
Once a drug formulation and dosing regime have been determined for the clinical trial, the search for a suitable manufacturer of the oral medication and lookalike placebo begins.
The requirements of the regulatory authorities regarding specifications for each and every ingredient in the formulation and the attendant documentation are exacting.
The medication must undergo various stages of monitoring and approval including the manufacturing process and shelf-life stability testing. This will involve a significant amount of time and significant expense.