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AD

AD-220 (AD 220A / AD 220 / AD220)

✓ Approved

Addpharma · 小分子 · 小分子

什么是 AD-220？

AD-220 是一种小分子，由Addpharma研发。该药已获批，用于治疗相关适应症，给药途径：Unknown。

药物档案

商品名AD 220A, AD 220, AD220
公司Addpharma
药物类别小分子
给药途径Unknown
状态Approved
来源： ClinicalTrials.gov, Addpharma

治疗适应症

AD-220 针对 2 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Metabolism and nutrition disordersHyperlipidaemia✓ Approved
Metabolism and nutrition disordersHypercholesterolaemiaPreclinical

相关研究文献

PubMedAllergy2026-08-06

Mycosis Fungoides-Like Atopic Dermatitis Represents a Th22-Dominant Inflammatory Endotype.

Lee Jung Ho JH, Lim Sung Ha SH, Kook Hyungdon H, Kang Seong-Jun SJ et al.

Early-stage mycosis fungoides (MF) often presents diagnostic challenges because of its clinical overlap with atopic dermatitis (AD). In clinical practice, we encountered a subset of patients with severe AD who fulfilled the MF diagnostic criteria yet remained clinically indistinguishable from AD and presented refractoriness to advanced therapies. We termed this ambiguous entity "mycosis fungoides-like AD" (mfAD) and sought to determine whether it represents malignant transformation or a distinct inflammatory endotype of AD. Skin biopsies were obtained from 7 patients with AD and 11 patients with mfAD. We performed paired single-cell RNA sequencing and single-cell T-cell receptor sequencing analyses. Publicly available MF and AD datasets were integrated for comparative analysis. Spatial transcriptomic profiling was used to contextualize single-cell findings within the tissue architecture. Comparative transcriptomic analysis revealed that T cells in mfAD were aligned with those in AD and lacked genomic instability. High-resolution profiling showed that mfAD was characterized by oligoclonal Th22 expansion rather than a single dominant malignant clone. Notably, all patients with mfAD achieved rapid clinical remission with selective JAK1 inhibition, indicating the therapeutic response characteristics of inflammatory dermatoses. Our findings demonstrate that mfAD is not a true malignancy, but rather a Th22-driven inflammatory endotype of AD. These results redefine mfAD as an inflammatory subtype within the AD spectrum, providing a mechanistic explanation for both the "pseudo-monoclonality" that leads to MF misdiagnosis and the failure of dupilumab. This study establishes a rationale for the use of JAK inhibitors in precision medicine for this patient population.

PMID 42560135
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PubMedAnnals of African medicine2026-08-06

Association of Serum Homocysteine and Vitamin B12 with Different Grades of Cognitive Impairment in Alzheimer's Disease Patients.

Mandal Tanima T, Sinharoy Uma U, Biswas Koushik K, Sarkar Pinaki P et al.

Studies have shown a relation between Vitamin B12 (B12) and cognitive impairment in Alzheimer's disease (AD). However, B12 levels do not indicate the severity of the disease. High homocysteine-induced neuroinflammation has been related to the pathogenesis of AD. This study aimed to determine the correlation of Vitamin B12 and serum homocysteine with the cognitive status of AD patients. AD patients (n = 25) and healthy controls (n = 25) were recruited for this study. The revised criteria for diagnosis and staging of AD were used for the diagnosis of AD. Clinical history, laboratory investigations (B12, homocysteine, lipid profile, C-reactive protein, and serum creatinine), and Mini-Mental Status Examination (MMSE) were done. Based on MMSE score, AD patients were subdivided into four groups. All statistical analyses were done on IBM SPSSv26. In AD patients, B12 was lower (221.3 ± 54.5 vs. 396.6 ± 88.4 pg/ml, P = 0.00), serum homocysteine was higher (15.2 ± 4.6 vs. 11.7 ± 2.3 µmol/L, P = 0.00), and C-reactive protein was higher (0.95 ± ± 0.39 vs. 0.69 ± 0.12 mg/dl, P = 0.00). Among the four AD groups, we observed a gradual increase in the serum homocysteine levels with a decline in the cognitive status (lower MMSE score) (F = 13.32, P = 0.00). MMSE score had a statistically significant correlation with homocysteine (ρ = -0.85, P = 0.00), unlike B12 (ρ =0.33, P = 0.11). Serum homocysteine is a better diagnostic indicator of cognitive impairment than B12. In resource-limited settings, screening with the Mini-Cog test and timely supplementation with B complex vitamins (B6, B12, and folic acid) can slow the progress of dementia in AD patients.

PMID 42560015
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PubMedAging cell2026-08-06

HNRNPC Succinylation Influences the Neurodegeneration of Alzheimer's Disease Through YME1L1-Mediated Mitochondrial Metabolism.

Li Xuewei X, Yang Fan F, Jiang Yuyan Y, Zhao Fei F et al.

Mitochondrial dysfunction and abnormal energy metabolism are important pathological features of Alzheimer's disease (AD). This study investigates how mitochondrial protease YME1L1 affects mitochondrial function and its upstream regulation in the pathogenesis of AD. The AD model was established by using APP/PS1 transgenic mice, primary neurons treated with Aβ1-42, and HT22 cells. The silencing of YME1L1 was achieved to evaluate its effects on mitochondrial function and OPA1 protein hydrolysis. RIP-qPCR and RNA pull-down test were used to evaluate the interaction between HNRNPC and YME1L1 mRNA. The protein succinylation level was detected by proteomic analysis of succinylation, and co-immunoprecipitation (Co-IP) was used to verify the succinylation of HNRNPC. Cognitive ability was tested by behavioral tests, including the Morris water maze, Y-maze, object recognition test, and olfactory test. Finally, the therapeutic potential of SIRT5 was studied by an overexpression experiment in an AD model. YME1L1 was significantly upregulated in the AD model, which promoted mitochondrial dysfunction and neuronal damage through OPA1 hydrolysis. HNRNPC enhances the stability of YME1L1 mRNA through an m6A-dependent mechanism, while its own K50 succinylation enhances the stability of HNRNPC by competitively inhibiting TRIM25-mediated ubiquitination, further amplifying the expression of YME1L1. SIRT5 downregulation in AD elevated HNRNPC succinylation levels. SIRT5 overexpression promoted HNRNPC desuccinylation, reduced YME1L1 expression, restored mitochondrial function, and ameliorated Aβ deposition and cognitive deficits in AD mice. The SIRT5-HNRNPC-YME1L1 axis contributes to AD pathogenesis by disrupting OPA1 proteolysis and mitochondrial dynamics. Targeting HNRNPC succinylation represents a promising therapeutic strategy for AD.

PMID 42557858
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PubMedMultiple sclerosis and related disorders2026-08-06

Clinical features of older MS patients with and without Alzheimer disease biomarkers.

Rodriguez Apollo A, Judge Bradley B, Shelley Nicole N, Mehta Vivek V et al.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by inflammatory demyelination and axonal injury. Magnetic resonance imaging (MRI) plays a central role in MS diagnosis. Recent work suggests that biomarkers indicative of Alzheimer's disease (AD) are markedly reduced in people with MS. Whether differences in AD biomarkers are related to different features of MS, including MRI characteristics or treatment history, is unclear. In this study, 100 MS patients from Washington University in St. Louis underwent review of their most recent MRI as well as their prior and present MS disease-modifying treatment (DMT) exposures. We then ascertained the relation of MRI features and DMT to plasma AD biomarker measurements, with only a small subset (N=7) demonstrating APS2+ biomarker evidence of AD. Lesion distribution across MS topographies and total white matter lesion (WML) burden were both similar across MS patients with and without biomarker evidence of AD. Central vein sign (CVS), a recently integrated imaging biomarker of MS, was highly prevalent across the MS cohort and did not differ by AD biomarker status or MS clinical typicality at diagnosis, supporting the MS diagnoses even for people with atypical initial presentations. DMT exposure history showed associations with AD biomarkers: longer exposure to B cell-depleting anti-CD20 monoclonal antibody therapies (BCDT) corresponded to lower levels of amyloid pathology as measured by plasma biomarkers, and longer exposure to interferon-beta corresponded to a less pathological Aβ42/40 ratio. These findings indicate that structural MRI features do not explain differences in AD biomarker profiles in MS, whereas treatment-related immunologic effects may contribute to variation in AD pathology risk in MS patients.

PMID 42556030
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PubMedBrain : a journal of neurology2026-08-06

Defining the underlying pathology of corticobasal syndrome using clinical features and biomarkers.

Vaughan David P DP, Jensen Marte Theilmann MT, Real Raquel R, Fumi Riona G RG et al.

Corticobasal degeneration (CBD) is a late onset progressive neurodegenerative condition of the 4-repeat-tauopathy-type, classically presenting with asymmetrical rigidity, dystonia and myoclonus. In the most recent diagnostic criteria, Armstrong and colleagues (2013) described four clinical phenotypes associated with this pathology, including corticobasal syndrome (CBS), through a large retrospective analysis of published cases and confirmed brain bank cases of CBD. However, predicting CBD pathology remains challenging. With the advent of disease-modifying therapies, it has become particularly important to distinguish Alzheimer's disease pathology from other underlying pathologies. We therefore combined two prospectively recruited cohorts of patients with CBS and analysed their key demographic, clinical and biomarker features. We included a separate cohort from UK brain banks who were diagnosed with CBS in life. We divided patients into three groups: CBS-Alzheimer's (CBS-AD), CBS-non-Alzheimer's (CBS-non-AD) and CBS-indeterminate (CBS-IDT) based on biomarkers and pathology, comparing clinical features, regional volumetric MRI measures and Nucleic Acid-Linked Immuno-Sandwich Assay with detection by next generation sequencing (NULISAseq) blood protein levels between groups. We performed additional analyses of pathologically verified cases. We included 397 participants, of which 57.7% were female. The mean age at symptom onset was 65.9 years. AD biomarkers and pathology permitted classifying 47 (11.8%) of the cases as CBS-AD, 134 (33.8%) as CBS-non-AD and 216 (54.4%) as CBS-IDT. Patients with CBS-AD had a younger age at onset (61.8 years vs 66.1 years, P < 0.01 and less severe motor deficits (non-significantly lower scores on MDS-UPDRS and PSPRS) and more severe cognitive impairment (non-significantly lower scores on MoCA). Patients with CBS-AD had higher rates of cortical sensory impairment (P = 0.087) and lower rates of limb dystonia (P < 0.01) and falls (P < 0.01) compared to the CBS-non-AD group. Volumetric MRI analysis revealed smaller parietal lobe volumes in CBS-AD (P = 0.01). The most common pathological diagnoses were PSP, CBD and AD. Limb dystonia was more common in people with CBD and PSP pathology (P = 0.077). Falls, impaired verbal fluency and impaired vertical saccades were confirmed as more common in PSP (P = 0.046, P = 0.040, P = 0.012, respectively). In summary, younger onset, less parkinsonism and more cognitive and cortical sensory impairment, along with reduced MRI parietal volumes point to CBS-AD, while limb dystonia, falls and worse verbal fluency relate to CBS-non-AD. Clinical, imaging and blood-biomarkers in can augment the Armstrong criteria in predicting the underlying pathology of corticobasal syndromes.

PMID 42557872
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PubMedAgeing research reviews2026-08-06

Mitochondrial homeostasis dysregulation: Potential mechanisms of Alzheimer's disease mediated by TDP-43.

Huang Wendi W, Huang Juan J, Kuang Nanyu N, Wu Jingjing J et al.

Alzheimer's disease (AD) exhibits substantial clinical and pathological heterogeneity that is not fully explained by amyloid-β and tau pathology alone. TAR DNA-binding protein 43 (TDP-43) is increasingly recognized as a frequent copathology in AD, particularly in limbic regions, where its presence is associated with accelerated cognitive decline. Disruption of mitochondrial homeostasis is also an early and consistent feature of AD and contributes to neuronal vulnerability. In this review, we summarize current evidence linking TDP-43 pathology to impaired mitochondrial homeostasis in AD. We outline key features of mitochondrial homeostasis in neurons, review neuropathological and clinical data supporting the relevance of TDP-43 in AD, and synthesize emerging mechanisms by which TDP-43 may perturb mitochondrial homeostasis, including effects on expression, aggregation and localization, quality control, organelle dynamics, and endoplasmic reticulum-mitochondria communication.

PMID 42556648
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