KDS2010 for Alzheimer's Disease — Phase 2 Clinical Trial
Trial Overview
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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 effectsMetabolic Effects : Additional mechanisms targeting brain energy metabolism and mitochondrial functionNeuroprotective 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 KDS2010Randomization : 1:1:1 ratioPrimary 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 distributionOff-target effects : MAO-A inhibition caused tyramine-induced hypertensionLimited disease-modifying potential : Mostly symptomatic effectsInadequate patient selection : Not targeting patients with elevated MAO-B activityKDS2010 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 |
Therapeutic Implications
Potential Benefits If successful, KDS2010 could represent[17][18]:
First disease-modifying MAO-B inhibitor for AD : Targeting upstream pathological processesCombination therapy potential : May synergize with [acetylcholinesterase inhibitors](/entities/ache-inhibitors) and anti-amyloid antibodiesNovel 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 effectsBiomarker-driven selection : Requires amyloid-positive patientsLong-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)
Related Pages
[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/) Show full description