Specifically detects endotoxins in AD blood
Biomarkers that reflect the underlying pathogenesis of Alzheimer’s disease (AD) would be helpful in understanding the mechanisms of disease and developing new therapeutic strategies. They would be also advantageous to early diagnosis, disease staging, assessing response to treatment, and evaluating the prognosis.
In the last decade, there have been remarkable advances in the developments of fluids and neuroimaging biomarkers for AD, including Aβ42, Aβ40, t-Tau and p-Tau in the cerebrospinal fluid and plasma, amyloid- and tau-positron emission tomography (PET), neurofilament light chain protein (NFL), and miRNAs.
Among the various alternatives to the classical amyloid cascade and tau hyperphosphorylation hypotheses for AD, the infectious theory has recently emerged. According to the infectious hypothesis, pathogens like gram-negative bacteria (GNB) are found in the AD patients. GNB and its endotoxins including lipopolysaccharides (LPS) can penetrate the blood brain barrier (BBB), trigger neuroinflammation, and affect AD pathology. Moreover, GNB endotoxins exist in the blood of AD patients at a high concentration.
Through the past years of research, DanDi Bioscience has found that the blood levels of GNB endotoxins are elevated in proportion to the severity of AD, suggesting the role as biomarkers for AD.
Based on this infectious hypothesis for AD and the possible role of endotoxins as biomarkers, DanDi Bioscience (hereafter ‘DanDi’ for short), a biotech pharmaceutical company headquartered in Seoul, is developing its innovative next-generation diagnostic kit, named ‘DD-A514’, for the early diagnosis of AD in conjunction with Plexense. Plexense based in Yongin, South Korea, has been specializing in the development and production of rapid and cost-effective kits for the early diagnosis of various diseases using its proprietary platform technology called ‘ACCEL ELISA’.
DD-A514 is a peptide-based molecule that binds specifically to the endotoxins in the blood of AD patients. Plexense’s technology will reinforce the sensitivity of DD-A514 and also allow the quantification of its effects. The ventures are expecting that they will commercialize DD-A514 by 2023 successfully.
The endotoxins released by GNB may be promising as biomarkers of AD. However, how specific these endotoxins are to AD remains an inevitable challenge to overcome because the blood levels of endotoxins are elevated not only in AD but also in other infectious or inflammatory diseases.
In parallel with DD-A514, DanDi is developing its novel peptide-based ‘DD-A279’ that targets LPS to treat AD, based on the infectious hypothesis. In the pre-clinical studies, DD-A279 reduced the AD pathologies and cognitive dysfunction in the AD animal models. Currently, DanDi is in preparation for a global Phase 1 clinical trial.
In collaboration with Dr. Yeong-Min Park of DanDi, Dr. Minho Moon of Konyang University has published a review paper titled ‘Gram-negative bacteria and their lipopolysaccharides in Alzheimer’s disease: pathologic roles and therapeutic implications.’ in the journal ‘Translational Neurodegeneration’ on December 7th. This paper reviewed the roles and pathomechanisms of gram-negative bacteria and LPS in AD.
Related Review Journals
Kim, H.s., Kim, S., Shin, S.J. et al. Gram-negative bacteria and their lipopolysaccharides in Alzheimer’s disease: pathologic roles and therapeutic implications. Transl Neurodegener 10, 49 (2021).
https://doi.org/10.1186/s40035-021-00273-y
Zetterberg, H., Bendlin, B.B. Biomarkers for Alzheimer’s disease—preparing for a new era of disease-modifying therapies. Mol Psychiatry 26, 296–308(2021).
https://doi.org/10.1038/s41380-020-0721-9
