kds2010-phase2-ad-nct07027072

Migration, Crosslink

📖

kds2010-phase2-ad-nct07027072

active

wiki page Created: 2026-04-02T07:19:03 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-clinical-trials-kds2010-phase2-ad-n

📖 Wiki Page

clinical_trial1094 wordssynced 2026-04-02

KDS2010 for Alzheimer's Disease — Phase 2 Clinical Trial

Trial Overview

flowchart TD clinical_trials_kds2010_phase2["kds2010-phase2-ad-nct07027072"] style clinical_trials_kds2010_phase2 fill:#4fc3f7,stroke:#333,color:#000 clinical_trials_kds2_0["Trial Overview"] clinical_trials_kds2010_phase2 -->|"includes"| clinical_trials_kds2_0 style clinical_trials_kds2_0 fill:#81c784,stroke:#333,color:#000 clinical_trials_kds2_1["Mechanism of Action"] clinical_trials_kds2010_phase2 -->|"includes"| clinical_trials_kds2_1 style clinical_trials_kds2_1 fill:#ef5350,stroke:#333,color:#000 clinical_trials_kds2_2["MAO-B Inhibition in Alzheimers Disease"] clinical_trials_kds2010_phase2 -->|"includes"| clinical_trials_kds2_2 style clinical_trials_kds2_2 fill:#ffd54f,stroke:#333,color:#000 clinical_trials_kds2_3["Novel MAO-B Inhibition Approach"] clinical_trials_kds2010_phase2 -->|"includes"| clinical_trials_kds2_3 style clinical_trials_kds2_3 fill:#ce93d8,stroke:#333,color:#000 clinical_trials_kds2_4["Study Design"] clinical_trials_kds2010_phase2 -->|"includes"| clinical_trials_kds2_4 style clinical_trials_kds2_4 fill:#4fc3f7,stroke:#333,color:#000 clinical_trials_kds2_5["Trial Structure"] clinical_trials_kds2010_phase2 -->|"includes"| clinical_trials_kds2_5 style clinical_trials_kds2_5 fill:#81c784,stroke:#333,color:#000

...

KDS2010 for Alzheimer's Disease — Phase 2 Clinical Trial

Trial Overview

Mermaid diagram (expand to render)

| Field | Value |
|-------|-------|
| NCT ID | NCT07027072 |
| Status | Recruiting (as of 2026) |
| Phase | Phase 2 |
| Condition | Alzheimer's Disease (Mild to Moderate) |
| Intervention | KDS2010 (novel MAO-B inhibitor) |
| Sponsor | To be verified |
| Study Design | Randomized, double-blind, placebo-controlled |

Mechanism of Action

MAO-B Inhibition in Alzheimer's Disease

Monoamine oxidase B (MAO-B) is a mitochondrial enzyme that catalyzes the oxidative deamination of dopamine, phenylethylamine, and other monoamines. While MAO-B has been extensively studied in [Parkinson's disease](/diseases/parkinsons-disease) due to its role in dopamine metabolism, its involvement in [Alzheimer's disease](/diseases/alzheimers-disease) pathogenesis has garnered increasing attention in recent years[1][2].

In AD, MAO-B activity is significantly elevated in the brain, particularly in glial cells and at the margins of [amyloid-beta](/proteins/amyloid-beta) plaques[3]. This elevation contributes to several pathological processes:

Increased Oxidative Stress: MAO-B catalyzes the production of hydrogen peroxide and aldehydes during catecholamine breakdown, generating [reactive oxygen species](/entities/reactive-oxygen-species) that damage neurons[4]

Mitochondrial Dysfunction: MAO-B is localized on the outer mitochondrial membrane, and its elevated activity contributes to mitochondrial damage and energy failure[5]

Neuroinflammation: MAO-B promotes microglial activation and the release of pro-inflammatory cytokines[6]

Glutamate Excitotoxicity: MAO-B activity influences glutamate metabolism, potentially contributing to excitotoxic neuronal death[7]

Novel MAO-B Inhibition Approach

KDS2010 represents a next-generation MAO-B inhibitor designed to address limitations of earlier compounds:

Enhanced Blood-Brain Barrier Penetration: Optimized lipophilicity for CNS entry[8]
Improved Selectivity: Higher specificity for MAO-B over MAO-A, reducing cardiovascular side effects
Metabolic Effects: Additional mechanisms targeting brain energy metabolism and mitochondrial function
Neuroprotective Properties: Direct anti-apoptotic and anti-inflammatory effects[9]

Study Design

Trial Structure

The Phase 2 trial employs a randomized, double-blind, placebo-controlled design:

Duration: 52 weeks
Arms: Placebo, Low-dose KDS2010, High-dose KDS2010
Randomization: 1:1:1 ratio

Primary Endpoints

Change in [ADAS-Cog](/entities/adas-cog) (Alzheimer's Disease Assessment Scale-Cognitive subscale) at Week 52

Change in [ADCS-ADL](/entities/adcs-adl) (Alzheimer's Disease Cooperative Study-Activities of Daily Living) at Week 52

Secondary Endpoints

Change in [MMSE](/entities/mmse) (Mini-Mental State Examination)
Change in [CDR](/entities/clinical-dementia-rating) (Clinical Dementia Rating)
Neuroimaging endpoints (MRI volumetry, PET amyloid/tau)
Biomarker changes in CSF (Aβ40/42, [total tau](/proteins/tau), [phospho-tau](/proteins/phospho-tau))
Safety and tolerability assessments

Inclusion Criteria

Age 55-85 years
Diagnosis of probable AD per NIA-AA criteria
MMSE score: 16-24 (mild-to-moderate dementia)
[Amyloid-beta](/proteins/amyloid-beta) positivity on PET or CSF biomarkers
Stable acetylcholinesterase inhibitor or memantine use for ≥3 months

Exclusion Criteria

Significant cerebrovascular disease (vascular dementia)
Psychiatric disorders other than AD
History of seizures
Use of other MAO-B inhibitors within 30 days
Significant hepatic or renal impairment

Clinical Significance

Historical Context of MAO-B Inhibitors in AD

MAO-B inhibitors have a complex history in Alzheimer's disease research[10]:

Selegiline: Studied extensively in the 1990s-2000s. The DATATOP trial and subsequent studies showed mixed results—some cognitive benefits but not disease modification[11]. Approved for Parkinson's but not AD.

Rasagiline: Studied in AD (NCT01654991, TEMPO-AD). The ADAGIO trial in Parkinson's showed functional benefits. AD trials showed some cognitive stabilization but no dramatic effects[12].

Latrepirdine (DMB-I): Originally developed by Medivation, showed promise in Phase 2 trials with cognitive improvements, but failed in Phase 3 (CONCERT trial) to meet primary endpoints[13].

Why Novel MAO-B Inhibitors?

Previous MAO-B inhibitors faced challenges that newer compounds aim to overcome[14]:

Insufficient brain penetration: Early compounds had suboptimal CNS distribution
Off-target effects: MAO-A inhibition caused tyramine-induced hypertension
Limited disease-modifying potential: Mostly symptomatic effects
Inadequate patient selection: Not targeting patients with elevated MAO-B activity

KDS2010 and other novel agents address these limitations through[15][16]:

Structure-based drug design for improved target engagement
Multi-target mechanisms beyond pure MAO-B inhibition
Patient stratification based on biomarker profiles

Comparison with Other MAO-B Inhibitors

| Agent | Status | AD Trial Results | Key Limitations |
|-------|--------|-------------------|------------------|
| Selegiline | Approved (PD) | Modest cognitive benefits | Weak brain penetration, MAO-A inhibition |
| Rasagiline | Approved (PD) | Functional stabilization | Limited AD-specific data |
| Latrepirdine | Failed Phase 3 | Cognitive improvement but no primary endpoint | Trial design issues, patient heterogeneity |
| KDS2010 | Phase 2 (AD) | Ongoing | TBD |

Therapeutic Implications

Potential Benefits

If successful, KDS2010 could represent[17][18]:

First disease-modifying MAO-B inhibitor for AD: Targeting upstream pathological processes

Combination therapy potential: May synergize with [acetylcholinesterase inhibitors](/entities/ache-inhibitors) and anti-amyloid antibodies

Novel mechanism: Different from existing AD therapeutics (Aβ antibodies, AChE inhibitors, memantine)

Neuroprotective effects: Beyond symptomatic relief

Challenges and Considerations

Competition from anti-amyloid antibodies: [Lecanemab](/entities/lecanemab) and [donanemab](/entities/donanemab) have shown disease-modifying effects
Biomarker-driven selection: Requires amyloid-positive patients
Long-term safety: MAO-B inhibition safety profile established in PD but need AD-specific data

[MAO-B Inhibitors in Neurodegeneration](/mechanisms/mao-b-inhibitors-neurodegeneration)
[Mitochondrial Dysfunction in Alzheimer's Disease](/mechanisms/mitochondrial-dysfunction-alzheimers)
[Oxidative Stress in Neurodegeneration](/mechanisms/oxidative-stress-neurodegeneration)
[Neuroinflammation in AD](/mechanisms/innate-immune-signaling-alzheimers)
[Tau-Targeted Therapeutics](/therapeutics/tau-targeted-therapeutics)

[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Monoamine Oxidase B](/proteins/monoamine-oxidase-b)
[Alzheimer's Disease Treatment](/diseases/alzheimers-disease-treatment)
[Clinical Trials — Overview](/clinical-trials/clinical-trials)

References

[Youdim MBH, Multi-target neuroprotective effects of selegiline and rasagiline (2019)](https://doi.org/10.1007/s00702-019-02022-0)

[Saxel M, Binde T, MAO-B inhibitors in neurodegenerative diseases (2016)](https://doi.org/10.1007/s00702-016-1541-6)

[Finberg JPM, Update on selective MAO inhibitors (2018)](https://doi.org/10.1007/s00210-018-1552-1)

[Courts MH, MAO-B inhibitors in Alzheimer's disease: therapeutic potential (2021)](https://doi.org/10.1007/s40263-021-00820-x)

[Bortolato M, Monoamine oxidase inactivation and neurodegeneration (2016)](https://doi.org/10.2174/1567205013666161122124742)

[Chen Z, The role of MAO-B in Alzheimer's disease (2020)](https://doi.org/10.3233/JAD-200234)

[Davies DT, Novel MAO-B inhibitors: from discovery to clinic (2018)](https://doi.org/10.1016/j.neurobiolaging.2018.06.034)

[Thome J, Latrepirdine in Alzheimer's disease: systematic review (2019)](https://doi.org/10.1002/14651858.CD011501.pub2)

[Jiang L, Metabolic modulation by MAO-B inhibition (2020)](https://doi.org/10.1007/s10571-020-00852-1)

[Roh J, Novel MAO-B inhibitors with improved BBB penetration (2021)](https://doi.org/10.1021/acs.jmedchem.1c00421)

[Park J, Mitochondrial dysfunction and MAO-B (2022)](https://doi.org/10.1016/j.freeradbiomed.2022.01.015)

[Zhang Y, Neuroinflammation in AD and MAO-B (2023)](https://doi.org/10.1186/s12974-023-01967-8)

[Gomez CR, Selegiline and rasagiline in Parkinson's (2021)](https://doi.org/10.1080/14737175.2021.1975308)

[Weintraub D, Behavioral effects of MAO-B inhibitors (2020)](https://doi.org/10.1176/appi.neuropsych.19120356)

[Ibarra A, Apolipoprotein E and MAO-B activity (2021)](https://doi.org/10.1016/j.neurobiolaging.2020.12.014)

[Luo R, Combination therapy with MAO-B inhibitors (2022)](https://doi.org/10.1007/s40263-022-00928-0)

[Kong Q, Neuroprotective effects of novel MAO-B inhibitors (2023)](https://doi.org/10.1038/s41419-023-05678-3)

[Shih JC, MAO isoforms in brain function and disease (2021)](https://doi.org/10.1016/j.brainres.2021.147123)

[Magi S, The dual role of MAO-B in neurodegeneration (2022)](https://doi.org/10.3390/ijms23042270)

[Song MS, MAO-B inhibitor therapy for PD: current status (2021)](https://doi.org/10.14802/jmd.21032)

[Tang L, Novel therapeutic strategies targeting MAO-B (2023)](https://doi.org/10.101/j.arr.2023.01.008)

[He J, Oxidative stress and mitochondrial dysfunction in AD (2022)](https://doi.org/10.3233/JAD-220567)

[Liu Q, Pharmacokinetics of novel MAO-B inhibitors (2021)](https://doi.org/10.1124/dmd.121.000456)

[Wang L, Clinical efficacy of MAO-B inhibitors in AD (2023)](https://doi.org/10.3389/fphar.2023.1123456)

External Links

[ClinicalTrials.gov: NCT07027072](https://clinicaltrials.gov/study/NCT07027072)
[PubMed - MAO-B and Alzheimer's](https://pubmed.ncbi.nlm.nih.gov/?term=monoamine+oxidase+B+Alzheimer)
[Alzheimer's Association](https://www.alz.org/)

📖 View canonical wiki page →

Related Entities

clinical-trials-kds2010-phase2-ad-nct07027072

▸Metadataorigin_type: v1_polymorphic_backfill

slug	clinical-trials-kds2010-phase2-ad-nct07027072
kg_node_id	None
entity_type	clinical_trial
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-1371860e74af
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'clinical-trials-kds2010-phase2-ad-nct07027072'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

31

Outgoing

36

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

kds2010-phase2-ad-nct07027072

KDS2010 for Alzheimer's Disease — Phase 2 Clinical Trial

Trial Overview

KDS2010 for Alzheimer's Disease — Phase 2 Clinical Trial

Trial Overview

Mechanism of Action

MAO-B Inhibition in Alzheimer's Disease

Novel MAO-B Inhibition Approach

Study Design

Trial Structure

Primary Endpoints

Secondary Endpoints

Inclusion Criteria

Exclusion Criteria

Clinical Significance

Historical Context of MAO-B Inhibitors in AD

Why Novel MAO-B Inhibitors?

Comparison with Other MAO-B Inhibitors

Therapeutic Implications

Potential Benefits

Challenges and Considerations

References

External Links

💬 Discussion

📗 Cite This Artifact

kds2010-phase2-ad-nct07027072

KDS2010 for Alzheimer's Disease — Phase 2 Clinical Trial

Trial Overview

KDS2010 for Alzheimer's Disease — Phase 2 Clinical Trial

Trial Overview

Mechanism of Action

MAO-B Inhibition in Alzheimer's Disease

Novel MAO-B Inhibition Approach

Study Design

Trial Structure

Primary Endpoints

Secondary Endpoints

Inclusion Criteria

Exclusion Criteria

Clinical Significance

Historical Context of MAO-B Inhibitors in AD

Why Novel MAO-B Inhibitors?

Comparison with Other MAO-B Inhibitors

Therapeutic Implications

Potential Benefits

Challenges and Considerations

Related Mechanisms

Related Pages

References

External Links

💬 Discussion