Drug Database
AD

AD-104 (AD104 / AD 104)

✓ Approved

Addpharma · Small Molecule · Small Molecule

What is AD-104?

AD-104 is a small molecule developed by Addpharma. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesAD104, AD 104
CompanyAddpharma
Drug ClassSmall Molecule
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Addpharma

Therapeutic Indications

AD-104 is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Metabolism and nutrition disordersHyperlipidaemia✓ Approved

Related Research Articles

PubMedFrontiers in nutrition2026-10-22

Time-restricted feeding during the inactive phase vs. ad libitum feeding: diet-dependent effects on weight and metabolic markers in male Wistar rats.

Hajhamidiasl Ladan L, Baş Murat M, Yilmaz Ozgur O, Ozer Samed S et al.

In recent years, intermittent fasting has become a popular method for preventing and treating obesity and chronic diseases. This study explored the metabolic and inflammatory effects of inactive-phase (Day) time-restricted feeding (TRF) vs. ad libitum feeding (Ad) in rats under high-fat (HF) and standard (S) diet for 8 weeks. Four groups (TRF + HF, TRF + S, Ad + S, Ad + HF; n = 7 each) were monitored for temporal changes in key biomarkers, including TNF-α, IL-6, LPS, insulin, glucose, and lipid profiles, and body weight. Baseline-adjusted two-way ANCOVA was used to evaluate the main effects of Diet and Feeding pattern and their interaction, with complementary multivariate analyses performed as sensitivity analyses. Body weight was significantly associated with both Diet and Feeding pattern after baseline adjustment, with the greatest observed weight gain in Ad + HF and the smallest in TRF + S. TNF-α showed a significant Diet × Feeding interaction, characterized by marked reductions in both TRF groups and little change in Ad + HF. Lipid metabolism exhibited distinct interactions between diet type and feeding regimens. Total cholesterol levels increased in both ad libitum-fed groups, whereas a reduction was observed in the TRF + S group. Triglyceride responses also showed pronounced treatment effects, with the TRF + HF group demonstrating the greatest decrease over the intervention period. IL-6, LPS, insulin, glucose, and LDL-C did not display significant group × time interactions. Overall, inactive-phase time-restricted feeding was associated with lower weight gain, favorable changes in selected lipid parameters, and a reduction in TNF-α. No significant Diet × Feeding interactions were observed for IL-6 or LPS, indicating that the inflammatory findings were specific to TNF-α rather than reflective of a generalized anti-inflammatory effect. However, because food intake was not quantitatively measured, these differences cannot be attributed to meal timing independently of possible differences in total energy intake.

PMID 42903068
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PubMedJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2026-10-21

EXPRESS: Synaptic density PET mediates the relationship between Alzheimer's disease pathology and cognitive performance.

McLachlan Max J MJ, Bettcher Brecca B, Langhough Rebecca R, DiFilippo Alexandra A et al.

Synaptic loss is one of the strongest post-mortem predictors of Alzheimer's disease (AD) severity and may impact how pathology affects cognition. This study compared regional [11C]UCB-J synaptic density across the AD continuum and evaluated the extent to which synaptic density mediates relationships between AD biomarkers. Seventy-two participants completed PET scans, MRIs, and cognitive testing. Participants were categorized into subgroups representing typical AD progression. Regional synaptic density was compared across subgroups and pathological variables. Standard mediation and moderated mediation analyses were performed using amyloid and tau as predictors/moderators and MoCA score as outcome. The amyloid+/tau+/impaired subgroup showed lower synaptic density than controls, particularly for transverse temporal, inferior parietal, and hippocampal regions (Cohen's d=1.60, 1.57, 1.50). Hippocampal synaptic density had the strongest associations with tau (β=-0.473); transverse temporal synaptic density had the strongest association with amyloid (β=-0.543) and age (β=-0.614). Eight of twelve assessed brain regions demonstrated significant indirect effects across mediation frameworks. The inferior parietal lobe showed the largest mediation for amyloid (45.3%) and tau (28.9%). These findings support the hypothesis that synaptic loss is a primary mechanism contributing to clinical AD and suggest that synaptic density imaging can provide complementary information to the existing AD framework.

PMID 42902482
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PubMedAlzheimer's & dementia : the journal of the Alzheimer's Association2026-10-21

H3K9me3 inhibition reverses Alzheimer's progression by restoring synaptic and immune proteostasis across the brain-retina axis.

Fuchs Dieu-Trang DT, Vit Jean-Philippe JP, Rentsendorj Altan A, Koronyo Yosef Y et al.

Epigenetic dysregulation is increasingly linked to aging and neurodegeneration, yet its contribution to retinal and brain pathology in Alzheimer's disease (AD) remains unclear. We quantified the repressive epigenetic mark histone H3 lysine 9 trimethylation (H3K9me3) in post mortem retinas and brains from donors spanning normal cognition, mild cognitive impairment, and AD dementia. Using a multi-enzyme methyltransferase panel, we characterized the in vitro inhibitory activity of ETP69, an epidithiodiketopiperazine, against suppressor of variegation 3-9 homologue 1 (SUV39H1) and other methyltransferases. In two transgenic AD mouse models (APPswe/PS1dE9 and APPswe/tauP301L/PS1tm1Mpm), we assessed ETP69 effects on cerebral H3 methylation, behavior, AD-like pathology, synaptic integrity, and proteomic profiles. H3K9me3 increased early across the AD continuum in both brain and retina, correlating with cognitive impairment and neuropathological burden. H3K9me3 levels were strongly correlated between matched brains and retinas (r = 0.72, p = 0.0002). ETP69 substantially inhibited SUV39H1 and several other methyltransferases in cell-free assays, while consistently reducing cerebral H3K9me3 in vivo relative to other histone marks assessed. In mice, pharmacological H3K9me3 reduction mitigated AD-like pathology, preserved synapses, and improved short- and long-term cognitive and visual performance. Proteomics revealed that H3K9me3 derepression re-established retinal and brain proteostasis and remodeled innate immune pathways and brain-derived neurotrophic factor/nerve growth factor-inducible protein (BDNF/VGF)-granin signaling. This study identifies H3K9me3 accumulation as a shared, reversible epigenetic contributor to AD across the retina-brain axis; its reduction represents a promising disease-modifying strategy, and the retina may provide an accessible readout of brain epigenetic dysfunction.

PMID 42902099
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PubMedPsychogeriatrics : the official journal of the Japanese Psychogeriatric Society2026-10-21

Resting-State and Task-State Dual-Paradigm fNIRS Study Reveals Dynamic Alterations in Brain Network Activity in Alzheimer's Disease With Behavioural and Psychological Symptoms.

Li Fang-Bo FB, Zeng Qi Q, Liu Shan-Wen SW, Zhu Jia-Wen JW et al.

Alzheimer's disease (AD) frequently presents with behavioural and psychological symptoms of dementia (BPSD), severely impacting prognosis. The dynamic brain network mechanisms remain unclear, and traditional neuroimaging faces limitations. Functional near-infrared spectroscopy (fNIRS) offers a unique approach to explore these mechanisms under natural conditions. To systematically compare brain region activation, signal complexity and network topology in AD patients with and without BPSD using resting-state and verbal fluency task (VFT) fNIRS paradigms. This cross-sectional study enrolled 48 AD patients (24 with BPSD, 24 without) and 25 normal controls (NC). fNIRS recorded hemodynamic changes in the frontal, temporal, parietal and occipital lobes during rest and VFT. Analyses included activation, time-frequency characteristics, functional connectivity and network topology. Partial correlations assessed links between fNIRS metrics and neuropsychological scores. In resting state, AD-BPSD showed altered coefficient of variation in left premotor and somatosensory cortices, and elevated information entropy in left dorsolateral prefrontal cortex (lDLPFC), versus NC and AD-non-BPSD. Functional connectivity abnormalities emerged between right frontal eye field-left somatosensory cortex, and right dorsolateral prefrontal cortex (rDLPFC)-left superior temporal gyrus (lSTG) (p < 0.05). During VFT, AD-BPSD had significantly lower lDLPFC and left somatosensory activation versus NC (p < 0.05), but increased signal fluctuation and power in right primary motor cortex (rM1) (p < 0.05), alongside reduced whole-brain clustering coefficient (p = 0.023). AD-BPSD was associated with altered brain functional patterns across resting and task states, involving sensorimotor and executive networks as well as altered interhemispheric coordination. These fNIRS-derived alterations provide exploratory evidence of altered brain functional patterns associated with BPSD and warrant further investigation in larger longitudinal studies.

PMID 42902444
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PubMedMolecular brain2026-10-21

Single cell RNA sequencing and emerging transcriptomic technologies in Alzheimer's disease cerebral organoids: a mini review.

Razak Maizatul Fazilah Abdul MFA, Tieng Francis Yew Fu FYF

Alzheimer's disease (AD), the most common cause of dementia worldwide, presents a formidable challenge due to its complex, multifactorial etiology, and limited translational success of existing models. Recent advances in stem cell biology have enabled the generation of three-dimensional human cerebral organoids which exhibit multicellular complexity and self-organisation, recapitulating key aspects of fetal brain development in vitro. This mini review highlights the landscape of AD modelling in human cerebral organoids. While studies using single cell RNA sequencing (scRNA-seq) form the core of this review, we also discuss single-nucleus RNA sequencing, computational deconvolution, and spatial approaches as translationally relevant extensions. We categorise current organoid research into distinct model types: (1) familial AD models driven by APP, PSEN1, and PSEN2 mutations; (2) sporadic AD models incorporating genetic APOE variants and environmental risk factors (serum exposure, pollutants, and viral reactivation); (3) tauopathy models highlighting astrocyte-driven metabolic disruption; (4) models featuring glial-immune interactions; and (5) emerging models of mitochondrial dysfunction as an early disease initiator. Across these categories, single cell technologies reveal critical alterations in lipid metabolism, synaptic programs, and glial-immune crosstalk. Finally, we review methodological innovations-drawing on non-AD developmental organoid studies such as region-specific patterning, morphodynamic control, and enhanced cellular diversity, which offer a roadmap for improving the physiological fidelity of next-generation AD organoid models. Ultimately, integrating these advanced cerebral organoid platforms with single cell technologies offer a powerful toolkit to dissect early disease mechanisms and accelerate the development of personalised therapeutics.

PMID 42902292
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PubMedJournal of advanced nursing2026-10-21

Beyond Visitation: Perceived Meaning of Family Involvement and Advance Directive Completion in Nursing Homes.

Chen Hou-Ju HJ, Feng Po-Chung PC, Huang Hsiu-Li HL, Tsai Hsiu-Hsin HH et al.

To examine factors associated with advance directive (AD) completion among nursing home residents in Taiwan, focusing on family visitation patterns and the perceived meaning of family involvement. A cross-sectional study. Data from 134 family caregivers and their corresponding nursing home residents from seven nursing homes in northern Taiwan were analysed. Family caregiver data were collected using validated questionnaires, including the Family Meaning of Nursing Home Visits (FMNHV) scale. Multiple logistic regression was conducted, with candidate variables specified based on the study's conceptual framework and prior literature and refined using AIC-based forward and backward stepwise selection. The AD completion rate was 34.3%. Completion was associated with residents' prior expression of end-of-life preferences (OR = 14.33, 95% CI = 4.39-46.80) and caregivers' awareness of ADs (OR = 4.20, 95% CI = 1.29-13.65). Compared with daily visits, weekly visits were associated with lower odds of completion (OR = 0.23, 95% CI = 0.07-0.81), as were visits lasting 61 min or longer compared with those lasting less than 30 min (OR = 0.16, 95% CI = 0.03-0.79). Higher scores on the FMNHV responsibility for care quality subscale were associated with greater odds of completion (OR = 1.24, 95% CI = 1.11-1.39). Family involvement in AD completion extends beyond visitation patterns to include the perceived meaning of involvement. Both behavioural and interpretive dimensions should be considered when understanding AD completion in nursing homes. Nurses should consider both visitation patterns and the perceived meaning of family involvement when facilitating discussions about AD completion with residents and their families. This study identifies family involvement-related factors associated with AD completion and provides insights for nursing practice, staff training and advance care planning in long-term care settings. We adhered to the STROBE guidelines. No patient or public contribution.

PMID 42902463
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