With last Saturday, 29th February, marking Rare Diseases Day, we wanted to continue spreading the awareness of a particular rare condition, Huntington’s disease. IXICO has continued to support the clinical development of new treatments of Huntington’s disease through our work with the biopharma industry to find treatments for this neurodegenerative disease, which currently has no cure.
Huntington’s disease (HD) is a rare, inherited genetic brain disorder that results in the progressive loss of both mental faculties and physical control. It is caused by a mutation in a single huntingtin gene (HTT), which triggers the formation of toxic huntingtin protein, mHTT. Affecting approx. 1 in 10,000 people, symptoms usually appear between the ages of 30 to 50 and worsen over a 10 to 25 year period. Ultimately, the weakened individual succumbs to pneumonia, heart failure or other complications. Presently, there is no effective treatment or cure for the disease, and current treatments focus on providing symptom relief, maximising function and optimising quality of life.
In response to a very real need for advanced treatment of HD, there has been a marked increase in the volume of activity within the clinical development space. New therapeutic studies are in progress, with further studies planned to test the safety and efficacy in large observational studies, initiated to further the understanding of the disease’s pathophysiology and progression. New PET tracers that bind to the mutant huntingtin protein are expected to go into first-in-man studies this year, with the aim of better outcome measures being designed and validated to enhance the assessment of patient outcomes. Additionally, the field has its eye firmly fixed on generating the data needed to support interventional studies in pre-manifest patients, where biomarkers and digital measures that can detect early signs and changes in disease pathology and patient behaviour will be invaluable.
Against this backdrop, IXICO have been instrumental in helping biopharma make better decisions in HD clinical trial design and delivery, provided through a combination of IXICO’s HD scientific knowledge and advanced AI algorithms developed for clinically-relevant imaging and for digital biomarkers that monitor changes resulting from disease progression and treatment intervention. Having played a pivotal role in standardising the acquisition of MRI data and characterising imaging biomarkers for key HD natural history studies, IXICO has continued to combat these challenges through the advancement of internal data analytics capabilities and operational site qualifications for many HD trials.
Through our ability to innovate quickly, IXICO has developed a library of AI algorithms that are able to more accurately and efficiently analyse MRI data from HD clinical trials, and provide a wider array of imaging metrics, such as regional measures of brain volume and atrophy, that are applicable and validated specifically for HD. These AI algorithms have been developed through IXICO’s propriety LEAP (Learning Embeddings for Atlas Propagation), a technology that provides expedited and fully automatic segmentation for the accurate measurement of whole-brain and regional volumes.
The striatum, primarily the caudate and putamen regions within the brain, is highly sensitive to progression in HD, with the volume and other changes in these regions used as a marker for interventions in clinical trials. The gold-standard method for segmentation of these structures is manual analysis, a process that is time and labour-intensive, incurs high costs and is subject to inter- and intra-rater variation. Through IXICO’s collaboration with University College London, our LEAP platform was developed as a fully automatic multi-atlas imaging method to deliver reproducible segmentation of the putamen and caudate within HD studies.
With the number of gene therapies in development rising significantly, accurate volumetric measures will be essential for safe and effective drug administration. LEAP has been shown to enhance the ability to identify patient safety events faster, thus advancing patient stratification methodologies for HD. To further enhance the data analysis turnaround times, the latest development of a deep learning model (a 3D convolutional neural network (CNN)) has shown to take an order of magnitude less time, with significantly fewer memory requirements and the ability to process multiple subjects simultaneously, in the order of seconds. IXICO’s platform has the ability to collect intra-operative MRI data and surgical plans, often required for when the mode of administration is intracranial.
We believe that, only by working together within the broader neuroscience community we can develop treatments for HD and other rare neurological diseases. Over the past 15 years, IXICO has worked closely with many consortia, charities and research groups to advance the imaging capabilities deployed in HD clinical trials. Our expertise in data analysis and regulatory qualification is supporting the efforts of a major clinical consortium called the Huntington’s disease Regulatory Science Consortium (HD-RSC), in order to develop the regulatory path to qualify imaging biomarkers for use in HD clinical trials and support future clinical trials.
We are optimistic that these advancements in data analytics will further enhance the vital insights gained from clinical studies and will help the HD community move one step closer to finding break-through treatments for HD.
Check out our poster presented last month at CHDI to find out more about the latest advancements in our LEAP platform.