Company: APM
Filing Date: 2025-12-05
Form Type: 424B5
Source: 0001213900-25-118752
Chunk: 304

Company: Aptorum Group Ltd
Filing Date: 2025-12-05
Form: 424B5
Chunk 304
---
45, 46-55, 56-65 and 66-75 years
old, DiamiR has analyzed the levels of CogniMIR miRNA panel during healthy aging and found that sex-dependent changes
in miRNA levels can reflect centrally regulated processes., including changes in hormone levels during menopause. Concentrations of certain
miRNAs peaked at different ages, 46-55-year-old and 56-65-year-old groups, respectively. This study provides an important insight
into biology of DiamiR’s brain-enriched miRNA biomarkers detectable in blood plasma.

(Aging, 2018 10:3017; Aging,
2018, 10:2557)

CIRCULATING ORGAN-ENRICHED miRNAs AS BIOMARKERS OF RETT SYNDROME

Rett syndrome (RTT) is a rare
(1 in every 10,000-15,000 live-born female births) neurodevelopmental disorder caused by mutations in the MECP2 gene that is characterized
by neurological regression, microcephaly, motor stereotypies, irregular breathing, and other physical defects. Although diagnostic MECP2
genetic testing is widely available for RTT, biomarkers of RTT, including minimally invasive, blood-based indicators of disease severity
and progression, are lacking. DiamiR is validating a sensitive assay for RTT staging/prognosis and disease and treatment monitoring.

Following the pilot study conducted
by DiamiR using four mouse models of the disease and human plasma samples, DiamiR has defined a panel of 44 miRNA biomarker candidates
and conducted a study evaluating their effectiveness as RTT biomarkers using plasma samples of 163 study participants, including 81 RTT
patients and 82 age-matched controls; all collected at the Montefiore Medical Center, Bronx, NY.

miRNA pairs/classifiers were
shown to effectively differentiate between RTT patients and control of three age groups (best classifier AUC=0.94 for <5-yr-olds, AUC=0.91
for 6-15-yr-olds, AUC=0.77 for >16-yr-olds). Several miRNAs were also shown to present efficient biomarkers of secondary pathology:
walking ability (AUC=0.82), hyperventilation/breathing problems (AUC=0.75), and epilepsy (AUC=0.89).

The data supports the development