levetiracetam low dose (AGB101) / AgeneBio - LARVOL DELTA

Speech-induced Platysma Myoclonus in an Older Adult With Cerebral Amyloid Angiopathy: A Diagnostic Pitfall (AAN 2026) - "Memantine was tolerated at 15 mg/day; rivastigmine was not. Speech-induced Platysma Myoclonus is an underrecognized cause of "vocal tics" and speech arrest in older adults. Focused observation during speech tasks and exclusion of bulbar and epileptic etiologies can prevent misattribution to anxiety. Low-dose levetiracetam offered clinically meaningful control."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Epilepsy • Hematological Disorders • Mood Disorders • Movement Disorders

Repurposed Drugs for Alzheimer's Disease: Integrating Mechanistic Efficacy and Global Feasibility Through a Translational Decision Matrix (AAN 2026) - "GLP-1 receptor agonists (liraglutide, semaglutide) achieved the strongest combined cognitive and biomarker signals (efficacy = 3) but low feasibility (1) due to cost and delivery complexity...In contrast, metformin, nilvadipine, lithium, and low-dose levetiracetam achieved moderate efficacy (1–2) and high feasibility (2–3), emerging as pragmatic global candidates... Repurposed Alzheimer's therapeutics occupy distinct translational niches: biologics (GLP-1s, GM-CSF) show strong mechanistic efficacy but limited scalability, while inexpensive oral agents (metformin, lithium, nilvadipine) offer feasible, population-level potential. The Efficacy–Feasibility Matrix provides a novel decision-analytic framework to rank repurposed drugs not only by biological promise but also by their readiness for global implementation, bridging clinical pharmacology with equitable access."

Clinical • Alzheimer's Disease • Candidiasis • CNS Disorders • Cognitive Disorders • Dementia • Infectious Disease • CSF2

The effect of physical activity on epileptic seizures and consequentlearning and memory impairment in electrical amygdala kindling model. (PubMed, Daru) - "Our study reveals that, in conjunction with levetiracetam, regular exercise can ameliorate the intensity and frequency of amygdala electrical kindling-induced epileptic seizures, as well as the consequent spatial memory and learning impairments."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy

Drug Development. (PubMed, Alzheimers Dement) - "Low-dose levetiracetam selectively enhanced executive function in mid-age APOE33 individuals, but did not modify performance in APOE4+ carriers, despite literature reporting brain hyperactivity in this at-risk group. Consistent with existing findings that an 18-month intervention with low-dose levetiracetam slows cognitive decline and brain atrophy in non-APOE4+ individuals with Mild Cognitive Impairment due to AD, this drug may be used prophylactically in those who don't carry an APOE4 risk variant. Ongoing future work must verify whether Levetiracetam modifies brain hyperactivity in APOE4+ individuals, and if so, what are the longer-term cognitive and neurological consequences of this intervention."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • APOE

Biomarkers. (PubMed, Alzheimers Dement) - "Extensive preclinical and clinical studies show that low dose levetiracetam normalizes aberrant network activity and restores inhibitory and excitatory network balance. The HOPE4MCI clinical trial shows that there is meaningful benefit on the CDR-SB over 18-month AGB101 treatment and a significant reduction in neurodegeneration in the non-carriers of ApoE-4 with MCI due to AD. These findings support the view that reducing hippocampal hyperactivity confers benefit and further testing of AGB101 in patients with MCI due to AD who are non-carriers of ApoE-4 is warranted."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE • FAP • GFAP

Assessment of Low-Dose Levetiracetam Prophylaxis for Patients with Moderate to Severe Traumatic Brain Injuries (ASHP 2025) - No abstract available

Clinical • CNS Disorders • Vascular Neurology

Population Pharmacokinetics of Intravenous Levetiracetam in Neurosurgical Patients: Dosage Optimization Based on CrCl and Mannitol Use. (PubMed, Pharm Res) - "Standard LEV prophylaxis dosing often yields inadequate exposure in neurosurgical patients. LEV clearance is influenced by CrCl and mannitol use, higher doses is required for patients with concurrent mannitol therapy."

Journal • PK/PD data • CNS Disorders • Epilepsy

Low vs. Standard Daily Doses of Antiepileptic Drugs in Newly Diagnosed, Previously Untreated Epilepsy(STANDLOW) (clinicaltrials.gov) - P4 | N=58 | Completed | Sponsor: Mario Negri Institute for Pharmacological Research | Active, not recruiting ➔ Completed | N=374 ➔ 58

Enrollment change • Trial completion • CNS Disorders • Epilepsy

Clinical Trial of AGB101 for Mild Cognitive Impairment (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: AgeneBio | N=60 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

Effects of Low-dose Levetiracetam on Clinical Symptoms, Cognition and Hippocampal Hyperactivity in Schizophrenia (clinicaltrials.gov) - P=N/A | N=18 | Completed | Sponsor: University of Colorado, Denver | Recruiting ➔ Completed | N=30 ➔ 18 | Trial completion date: Jun 2024 ➔ Sep 2024 | Trial primary completion date: Jun 2024 ➔ Sep 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

AGB101-CN: Clinical Trial Evaluating the Efficacy of AGB101 for Reducing Hippocampal Overactivity in Older Adults (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Johns Hopkins University

New P2 trial • Alzheimer's Disease • CNS Disorders • Dementia

The Bidirectional Relationship Between Epilepsy and Alzheimer's Disease. (PubMed, Curr Neurol Neurosci Rep) - "Anti-seizure medications (ASMs), particularly low-dose levetiracetam, show potential not only for seizure control but also for mitigating amyloid deposition, tau hyperphosphorylation, and cognitive decline...The bidirectional nature of AD and epilepsy emphasizes the need for integrated diagnostics, including EEG and biomarker assessments, to guide early intervention and targeted therapies. Future research should focus on the mechanistic interplay between amyloid, tau, and hyperexcitability, alongside trials of ASM regimens, to refine therapeutic strategies and improve outcomes in this population."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Epilepsy • Geriatric Disorders

Biomarkers. (PubMed, Alzheimers Dement) - "As reported in Mohs et al. (2024), progression on the primary clinical/cognitive endpoint of the Clincial Dementia Rating Scale Sum of Boxes score (CDR-SB) occurred over the 78-week protocol in the HOPE4MCI study and non-carriers of ApoE4 treated with AGB101 showed a substantially more favorable effect than carriers. Here we report that treatment with AGB101, in those participants significantly reduced atrophy of the entorhinal cortex. That reduction in atrophy was significantly coupled with the change in CDR-SB and with plasma biomarkers of disease. These exploratory analyses would be consistent with a reduction in neurodegeneration in the non-carriers of ApoE4 treated with AGB101 prior to a clinical diagnosis of dementia."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE • GFAP

Alzheimer's Imaging Consortium. (PubMed, Alzheimers Dement) - "As reported in Mohs et al. (2024), progression on the primary clinical/cognitive endpoint of the Clincial Dementia Rating Scale Sum of Boxes score (CDR-SB) occurred over the 78-week protocol in the HOPE4MCI study and non-carriers of ApoE4 treated with AGB101 showed a substantially more favorable effect than carriers. Here we report that treatment with AGB101, in those participants significantly reduced atrophy of the entorhinal cortex. That reduction in atrophy was significantly coupled with the change in CDR-SB and with plasma biomarkers of disease. These exploratory analyses would be consistent with a reduction in neurodegeneration in the non-carriers of ApoE4 treated with AGB101 prior to a clinical diagnosis of dementia."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE • GFAP

Clinical Trial of AGB101 for Mild Cognitive Impairment (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: AgeneBio | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

Clinical Trial of AGB101 for Mild Cognitive Impairment (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: AgeneBio | Phase classification: P3 ➔ P2 | N=1040 ➔ 60

Enrollment change • Phase classification • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APOE

The HOPE4MCI study: AGB101 treatment reduces entorhinal cortex atrophy in patients with amnestic mild cognitive impairment due to Alzheimer’s Disease who are ApoE-4 non-carriers (AAIC 2024) - "As reported in Mohs et al. (2024), progression on the primary clinical/cognitive endpoint of the Clincial Dementia Rating Scale Sum of Boxes score (CDR-SB) occurred over the 78-week protocol in the HOPE4MCI study and non-carriers of ApoE4 treated with AGB101 showed a substantially more favorable effect than carriers. Here we report that treatment with AGB101, in those participants significantly reduced atrophy of the entorhinal cortex."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE • GFAP

The HOPE4MCI study: AGB101 treatment reduces entorhinal cortex atrophy in patients with amnestic mild cognitive impairment due to Alzheimer's Disease who are ApoE-4 non-carriers (AAIC 2024) - "As reported in Mohs et al. (2024), progression on the primary clinical/cognitive endpoint of the Clincial Dementia Rating Scale Sum of Boxes score (CDR-SB) occurred over the 78-week protocol in the HOPE4MCI study and non-carriers of ApoE4 treated with AGB101 showed a substantially more favorable effect than carriers. Here we report that treatment with AGB101, in those participants significantly reduced atrophy of the entorhinal cortex."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE • GFAP

Low vs. Standard Daily Doses of Antiepileptic Drugs in Newly Diagnosed, Previously Untreated Epilepsy(STANDLOW) (clinicaltrials.gov) - P4 | N=374 | Active, not recruiting | Sponsor: Mario Negri Institute for Pharmacological Research | Unknown status ➔ Active, not recruiting | Trial completion date: Dec 2021 ➔ Aug 2024 | Trial primary completion date: Jul 2021 ➔ Jun 2024

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Effects of Low-dose Levetiracetam on Clinical Symptoms, Cognition and Hippocampal Hyperactivity in Schizophrenia (clinicaltrials.gov) - P=N/A | N=30 | Recruiting | Sponsor: University of Colorado, Denver | Trial completion date: Dec 2023 ➔ Jun 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

The HOPE4MCI study: A randomized double-blind assessment of AGB101 for the treatment of MCI due to AD. (PubMed, Alzheimers Dement (N Y)) - "The possibility that ApoE-4 carriers and noncarriers will respond differently to therapeutic intervention is consistent with recently reported findings from biologics and the present results show further testing of AGB101 in patients with MCI due to AD who are noncarriers of the ApoeE-4 allele is warranted. Conclusions from the HOPE4MCI study are limited primarily due to the small sample size and results can only be regarded as a guide to future research."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE

Effect of Levetiracetam on Cognition: A Systematic Review and Meta-analysis of Double-Blind Randomized Placebo-Controlled Trials. (PubMed, CNS Drugs) - "This exploratory study suggests that levetiracetam might improve executive function in specific populations. However, the diversity in study populations and potential publication bias warrant caution."

Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • Fatigue • Pain • Psychiatry • Schizophrenia

Dosage, time, and polytherapy dependent effects of different levetiracetam regimens on cognitive function. (PubMed, Epilepsy Behav) - "When taken in small doses, for brief periods as monotherapy, levetiracetam minimally influences cognition. At higher doses, as part of long-term seizure management, in conjunction with multiple ASMs, LEV is associated with cognitive impairment."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Epilepsy • Psychiatry

Efficacy of Low Dose Levetiracetam for Status Epilepticus in Pediatric Patients: A Retrospective Study (ASHP 2023) - No abstract available

Retrospective data • Epilepsy • Pediatrics

AGB101 PDP: Clinical Trial Evaluating the Efficacy and Safety of AGB101 for Treatment of Parkinson's Disease Related Psychosis (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Johns Hopkins University | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry