Asceneuron SA today announces the publication of peer-reviewed data in the journal ACS Chemical Neuroscience regarding ASN90, an O–GlcNAcase (OGA) inhibitor, and one of its leading candidates in clinical development for treating neurodegenerative proteinopathies.
Neurodegenerative proteinopathies such as Alzheimer’s and Parkinson’s disease are characterized by the intracellular formation in the brain of insoluble and toxic protein aggregates, such as the microtubule-associated protein tau and α-synuclein respectively, that are closely linked to disease progression. OGA is an emerging drug target in central nervous system drug development since deficient glycosylation of these intracellular proteins has been associated with neuronal dysfunction. OGA inhibitors prevent the elimination of intracellular protein glycosylation, thereby halting the decline of the healthy-state levels of this post-translational modification and preventing the formation of toxic protein aggregates.
In this recently published, peer-reviewed paper, Asceneuron reports the preclinical discovery and development of the novel small molecule OGA inhibitor ASN90 (formerly known as ASN120290/ASN561), which has already completed testing in three Phase I studies in healthy young and elderly subjects. The preclinical data show that daily oral administration of ASN90 prevented the development of tau tangle pathology, as well as functional deficits in motor behavior and breathing, and increased survival. Another significant finding; novel for this class of molecules; is that ASN90 slowed the progression of motor impairment and reduced astrogliosis in a frequently utilized, preclinical model of Parkinson’s disease.
Asceneuron currently has an open investigational new drug (IND) application with the US Food and Drug Association (FDA) for a Phase 2/3 study to evaluate ASN90 in progressive supranuclear palsy (PSP), an orphan indication. PSP is a rare neurological condition that causes severe problems with walking, balance, speech, swallowing and vision as a result of the accumulation of aggregates of the tau protein in the brain. The disease gets progressively worse, with people becoming severely disabled within three to five years of onset. It is estimated that three to six people per 100,000 will develop PSP and there is currently no cure for the disease.
Dirk Beher, Chief Executive Officer, Co-Founder of Asceneuron and senior author of the study, commented: “We are very excited to publish such key encouraging preclinical data on ASN90 and OGA mechanism of action. These findings provide a strong rationale for the development of OGA inhibitors as disease-modifying agents in both tauopathies and α-synucleinopathies such as Alzheimer’s, PSP, and Parkinson’s disease. Since tau and α-synuclein pathologies frequently co-exist in neurodegenerative diseases, OGA inhibitors represent unique, multimodal drug candidates for multiple indications. We continue to progress our clinical development with our latest once a day OGA inhibitor, ASN51, which will be dosed in Alzheimer’s disease patients in the forthcoming months.”