conceptual period

Recipient: Hanover Medical School (MHH)
Funding: Go-Bio initial (01/10/2022 to 30/09/2023, EUR 117,287.16)

The treatment, including the prophylaxis, of neurodegenerative diseases, such as Alzheimer's disease, is one of the major challenges of the coming decades. Polysialic acid (PolySia) is essential for the regular development and function of the nervous system and is necessary at the molecular level for maintaining a balance of N-methyl-D-aspartate receptor-controlled signal transmission. It is precisely this balance that is disturbed in ageing and dementia. In many situations PolySia effects depend on the degree of polymerisation (DP), which is diverse in the biological system. To clarify the structure-function relationship, PolySia of bacterial origin was isolated. By means of chromatography, a method for separating substances, individual DPs were obtained. Using a mouse model of Alzheimer's disease, a reconstitution of memory to the level of the control animals was found after a specific single intranasal administration of DP10 or DP12. 

The aim of the CogniSia project is length-controlled PolySia production while avoiding the cultivation of PolySia-producing human pathogenic bacteria due to the safety risk and low yield. Therefore, a cell-free expression system, which can produce high-purity PolySia very efficiently, is to be developed. Molecules obtained in this way could in the future initially be used as dietary supplements as part of a spin-off to prevent neurodegenerative diseases and improve cognitive performance. 

feasibility stage

Recipient: Hanover Medical School (MHH)
Funding: GO-Bio initial feasibility phase 3 (01/10/2023 to 30/09/2025, EUR 1,087,714.86)

Neurodegenerative diseases and age-related cognitive decline affect many millions of people and cause immense socio-economic burden. There are currently no curative therapy strategies to help those affected and their relatives and to reduce the burden on the health system. Treatment to support cognitive function in old age, including the prophylaxis of neurodegenerative diseases, is one of the major challenges of the next few decades – worldwide.  

Polysialic acid (PolySia) is essential for the regular development and function of the nervous system and is necessary for maintaining a balance in the brain necessary for memory. However, it is precisely this balance that is disturbed in ageing and dementia. Based on preliminary work in the exploratory phase the CogniSia-2 project pursues the feasibility phase goal to further develop PolySia of defined polymer size (DP) in such a way that it can be used as a pure substance for research and analysis purposes and, primarily, as a therapeutic agent and for the prophylaxis of neurodegenerative diseases. Importantly, PolySia DP10-12 has been shown to have a positive effect on neurodegeneration and associated cognitive decline in animal models. As part of the project the production platform for enzyme catalysis-based, cost-effective and length-controlled production of PolySia DP10-12 is to be expanded and transferred to an industrial scale. The toxicity of PolySia DP10-12 will additionally be tested in animal experiments as well as in cell culture-based models and the underlying mechanisms of action will be examined.