Advantages
- Persistent duration of action achieved.
- Physiological function of αSyn preserved.
- Applicable to both sporadic and hereditary cases.
- Broadly applicable across synucleinopathies.
Background and Technology
Parkinson’s disease is a neurodegenerative disease in which degeneration of dopaminergic neurons in the substantia nigra of the midbrain leads to motor symptoms including akinesia, rigidity, and tremor, as well as non-motor symptoms such as mental and cognitive dysfunction and autonomic dysfunction. Conventional treatments include symptomatic treatments such as dopamine supplementation and deep brain stimulation, but no disease-modifying therapy has been developed.
On the other hand, the core of the pathology is understood to be the formation of aggregates of αSyn, a key component of Lewy bodies, and researches of knockdown of αSyn gene, SNCA, using antisense oligonucleotides (ASOs) have been reported. However, SCNA knockdown ASOs require frequent administration because their structural moieties do not ensure sufficient duration of pharmacological action, and because there is concern about the risk of adverse events including post-lumbar puncture syndrome in diseases such as Parkinson’s disease that require long-term treatment. Additionally, αSyn is considered to have a role in synaptic function regulation, and there is also concern that αSyn knockdown may compromise neurophysiological functions.
Here we have developed a nucleic acid compound that inhibits aggregate formation without knocking down αSyn. Compared to SNCA knockdown ASO, it has the advantage of a longer duration of action and preferable maintenance of the physiological function of αSyn. It is also applicable for both sporadic and hereditary cases, and can be further applied across synucleinopathies (Lewy body dementia, multiple system atrophy).
Reference and Patents
- Patent pending (unpublished yet)
Principal Investigator
Masahisa KATSUNO (Department of Neurology, Nagoya University Graduate School of Medicine)
Current Stage and Next Step
- It has been confirmed by in vitro and/or in vivo assays that our unique nucleic acid compound suppresses αSyn expression and in turn αSyn aggregation.
- We are currently verifying the effects of the nucleic acid compound on alleviation of neurodegeneration as well as motor dysfunction in a platform of a Parkinson’s disease model mouse.
- We plan to verify a favorable pharmacokinetics and safety of the nucleic acid compound in non-human primates and conduct clinical trials in the future.
- We are looking for collaborative partner companies for both preclinical and clinical development of the nucleic acid compound as a Parkinson’s disease drug.
Project No. BK-04061