Company: APM
Filing Date: 2025-10-06
Form Type: S-4
Source: 0001213900-25-096656
Chunk: 356

Company: Aptorum Group Ltd
Filing Date: 2025-10-06
Form: S-4
Chunk 356
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 other approaches reflect the current opinion of the management based on its experience with technology to date and data reported in peer reviewed DiamiR’s publications listed elsewhere in this document. 200 Innovative technology developed by DiamiR addresses some of the limitations of these approaches. DiamiR hypothesizes that changes in plasma levels of circulating miRNAs known to be enriched in specific regions of the brain involved in a disease pathology are more likely to reflect associated pathologic processes than changes in levels of ubiquitous miRNAs or other brain -enrichedmiRNAs. DiamiR analyzed expression and secretion of neurite/synapse specific miRNAs, which could be affected by neurite/synapse dysfunction and destruction characteristic of early stages of neurodegeneration. Since these cellular neurodegenerative processes occur 10+ years prior to any manifestation of dementia and Alzheimer’s symptoms, a miRNA testing platform has the potential to identify at -risksubject years before symptoms arise. To compensate for processes unrelated directly to a disease pathology, e.g. changes in blood -brainbarrier permeability, DiamiR employed the “biomarker pair” approach normalizing levels of miRNAs enriched in neurons of affected brain areas by levels of other brain -enrichedmiRNAs expressed in brain areas or cell types not involved in early stages of disease pathology. DiamiR has also found that high correlation of plasma concentrations of miRNAs in a candidate biomarker miRNA pair is critical for achieving high sensitivity and specificity of the pair as a biomarker. This finding significantly improves the selection of optimal miRNA pairs. Advantages and disadvantages of “Organ/Cell Specific Analysis” developed by DiamiR vs.other approaches to identifying miRNA biomarkers are summarized in the table above. In summary, miRNAs are powerful biomarkers, because: •Certain miRNAs are enriched in •specific organs in the body (e.g. brain) •organ regions or tissues in an organ (e.g. hippocampus) •cell types (e.g. neurons) •cellular compartments within a cell (e.g. neurites, synapses) •miRNAs appear in blood because they •are secreted/excreted into extracellular space in normal cellular processes •can cross the blood -brainbarrier •are stable in circulation •Mature technologies are available for miRNA detection •miRNAs are reflective of the biology of the disease at the time of biological samples are collected •miRNAs are stable analytes and can be handled