About neurodegenerative disorders
Neurodegenerative disorders and the role of miRNA
Neurodegenerative disorders are chronic conditions that destroy parts of the nervous system over time, especially the brain. They result in progressive loss of cognitive and motor function and eventually, death. The most common neurodegenerative diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), Motor neuron disease (MND), Huntington’s disease (HD), Spinal muscular atrophy (SMA), and Spinocerebellar ataxia (SCA). While many of these conditions are more common in people over 65, some such as Huntington’s disease and ALS can appear much earlier, often in mid-life.
Research to date has demonstrated the involvement of miRNAs within neurogenerative disorders, with a number of particularly compelling targets.
Harness’ MISBA® platform
At the heart of Harness’ innovation is MISBA®, our proprietary platform for controlled modulation of protein expression to allow targets with a narrow therapeutic window to be safely addressed. This approach is unlocking disease-modifying targets previously out of reach with conventional platforms.
The MISBA® platform harnesses the complex regulatory mechanism enacted by miRNA networks in the CNS. Modulating this mechanism provides a way to make small, controlled changes to target proteins, but requires a specific and tuneable intervention.
The MISBA® (microRNA steric blocking ASO) platform enables us to design simple oligonucleotide drugs which bind to the target mRNA and block the two most important miRNA sites, providing precise modulation of the target protein.
While most therapeutic platforms can induce extreme up or downregulation of target activity, MISBA® enables tuneable, self-limited protein upregulation without disrupting the miRNA environment, as would be the case for ‘antimiR’ approaches which target the miRNAs themselves.
Second generation platform: MISBA® Duo
Harness has recently launched MISBA® Duo, which builds on the existing platform to enable simultaneous upregulation of one target with downregulation of a second. The platform combines MISBA® and GAPmer ASO functionalities to achieve dual mechanisms of action. This approach paves the way for advanced disease-modifying approaches to neurodegenerative diseases and other CNS disorders.
Target discovery and validation for CNS
Our discovery platform has been built to identify and validate features which determine the translation efficiency of each target we work on, guiding us to the best strategy and technology for each target.
Key features of our platform include:
Rapid hotspot identification
- Proprietary upregulation hotspot identification pipeline combines RNA analytics, cell line and patient datasets in proprietary bioinformatics tool
- We evaluate potential upregulation features throughout the whole mRNA, not just the coding sequence, to maximise performance for each target
Sophisticated screening platform and disease models
- High-throughput precision upregulation analytics
- Highly disease-relevant iPSC, neuronal and organoid models ensure rapid candidate optimisation and translatability
MISBA® ASOs
- Proprietary bispecific ASO technology using clinically precedented chemistry
- Drives cell specific controlled upregulation of 1 or 2 targets with a single construct
- Highly developable and compatible with a range of delivery strategies