Date: 2012-03-06
Type of information:
phase: in vivo non clinical studies
Announcement: presentation of data at AD/PD™ 2013, the international conference on Alzheimer’s and Parkinson’s diseases held in Florence, Italy, 6-10 March.
Company: Summit (UK)
Product: OGA (O-linked N-acetylglucosaminidase) inhibitor programme
Action mechanism:
Disease: tauopathies including Alzheimer’s disease
Therapeutic area: Neurodegenerative diseases
Country:
Trial details:
Latest
news: * On March 11, 2013, Summit, a drug discovery and development company, has reported new data from its OGA (O-linked N-acetylglucosaminidase) inhibitor programme for the treatment of tauopathies, a group of neurodegenerative diseases that includes Alzheimer’s disease. The study evaluated the OGA inhibitors, previously identified using Seglin™ technology, in a transgenic tauopathy disease model to determine the effect that prolonged dosing had on motor impairments related to the disease and survival rates. The tauopathies are also characterised by reduced levels of O-GlcNAcylated tau protein and raised levels of hyper-phosphorylated tau protein.
In summary, the results of daily oral dosing with the Seglin inhibitors for 10 weeks were:
• A clear trend for reduced clasping, a clinical sign indicative of motor impairment, and improved survival rates compared to the untreated cohort;
• A statistically significant increase in O-GlcNAcylated protein levels in the brain with the increased global levels maintained on repeat dosing to demonstrate that the OGA inhibitor accessed the brain compartment at therapeutically relevant concentrations;
• No observed change in tau protein phosphorylation levels although this is consistent with precedent from the scientific literature;
• No associated toxicity or adverse effects from prolonged dosing observed.
* On March 6, 2012, Summit has reported new data from in vivo studies in its drug discovery programme targeting Alzheimer’s disease and related neurodegenerative disorders. The programme has been developed using Summit’s proprietary Seglin™ technology drug discovery platform.
Recent independent scientific publications have placed greater emphasis on the importance of tau and neurofibrillary tangles (NFTs) in the cause and spread of Alzheimer’s disease. Additional studies have highlighted how inhibiting the enzyme O-linked N acetylglucosaminidase (‘OGA’) can prevent tau from aggregating and forming NFTs, confirming it as a target for the development of potential disease modifying drugs to treat Alzheimer’s. Using Seglin™ technology, Summit has identified, as previously reported, potent and highly selective Seglin inhibitors of O-linked N-acetylglucosaminidase (OGA) and has established in vitro efficacy in human cell models of Alzheimer’s disease.
However, the latest in vivo, non-clinical studies evaluated the pharmacokinetic properties (or properties pertaining to the movement of drugs within the body) of these potent Seglin inhibitors and the results showed that they were able to penetrate the Blood Brain Barrier (‘BBB’) and enter the central nervous system (‘CNS’). This is an important prerequisite for treating CNS disorders as delivery of drugs to the brain represents the major challenge when developing medicines for their treatment.
Furthermore the Seglins also displayed excellent bioavailability with the compounds being rapidly absorbed when administered orally. Importantly, no adverse effects were reported from these in vivo studies. These data represent a significant step forward in the development of this programme.
