Annovis Bio Measures Novel Biomarkers in Plasma of Parkinson’s Patients

Recent developments in biomarker research have enabled the performance of measurements of important biomarkers in plasma rather than in CSF (cerebrospinal fluid), making it possible to follow the changes in biomarkers during the course of a neurodegenerative disease while reducing patients’ burden.

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The figure shows the protein levels of biomarkers in PD patients’ plasma treated with either placebo (n=5) or 80mg buntanetap (n=10) at Day 28/End of Treatment. (Graphic: Business Wire)

TDP-43 (TAR DNA-binding protein 43) was discovered by Lee & Trojanowski at the University of Pennsylvania in 2007, and was suggested to be associated with frontotemporal dementia (FTD, 1),. Shaw’s lab in King’s College London associated TDP43 with amyotrophic lateral sclerosis published in Science 2008 (ALS, 2). More recently a number of papers in high profile journals have associated the protein with other neurodegenerative diseases, such as Alzheimer’s disease (AD, 3,4,5,8,9) and Parkinson’s disease (PD, 6,7). Of special interest, Dr. Ron Peterson from the Mayo Clinic pointed out in his 2018 Neurology review that protein abnormalities beyond amyloid and tau, including TDP-43 and α-synuclein, may contribute to neurodegeneration and cognitive impairment (5).

TDP-43 turns out to be a neurotoxic aggregating protein that has a normal function at normal levels, but when overexpressed it aggregates and becomes toxic, just like Aβ and α-synuclein. It impairs axonal transport, induces inflammation, and kills nerve cells.

Two years ago, Annovis found that buntanetap inhibited expression of TDP43 in vitro through an unbiased proteomics search of proteins whose translation is regulated by buntanetap as published (10) and in table below. Now we were able to see a decrease of TDP43 in plasma of PD patients from our phase 2a study. This was made possible through the new Quanterix Simoa TDP43 assay, which detects both full-length and pathological, truncated forms of the protein. The data revealed that 80mg buntanetap treatment (n=10 patients) indeed reduced the accumulation of TDP43 in patients’ plasma by 71.7% compared to placebo (n=5 patients), with a statistically significant difference between placebo and treated p=0.05. Buntanetap also showed a trend in reducing inflammatory factor GFAP (Glial fibrillary acidic protein) and the axonal damage biomarker NfL (Neurofilament-light chain).