By: Archana Murugan, PharmD Candidate c/o 2029
Introduction
Alzheimer’s disease (AD) refers to a progressive neurodegenerative form of dementia, affecting a person’s memory, cognitive function, and ability to perform daily activities worldwide. Presently, more than 6 million Americans aged 65 years and older are living with Alzheimer’s disease, indicating that as the population continues to age, disease prevalence is expected to rise.1
The accumulation of abnormal protein masses, called amyloid plaques and neurofibrillary tau tangles, disrupts the normal functioning of brain cells. Initially, this this causes memory impairment, followed by affecting areas responsible for language, reasoning, and social behavior; eventually, many other regions of the brain are affected.1 With no absolute cure for Alzheimer’s disease, it remains the seventh leading cause of death in the United States.
The Role of Tau in Alzheimer’s Disease
Tau is a microtubule-associated protein which, in a healthy adult, regulates the assembly and maintenance of microtubules, contributing to neuronal structural stability. 2 Simply put, tau stabilizes a neuron’s internal structure allowing the cell to function properly. However, in individuals diagnosed with AD, tau becomes hyperphosphorylated, leading to microtubule disassembly and aggregation into paired helical filaments forming neurofibrillary tangles.
Essentially, instead of stabilizing, tau becomes pathologically clumped within neurons, impairing neuron-to-neuron communication. This effect is triggered by accumulation of beta-amyloid particles outside neurons which disrupt normal cellular signaling leading to abnormal tau protein modifications inside the neurons.2 Due to tau’s central role in disease progression, targeting pathological tau through therapeutic intervention represents a promising strategy for Alzheimer’s disease treatment.
ADEL-Y01
ADEL-Y01 is an emerging therapeutic approach aimed at slowing the progression of Alzheimer’s disease, currently in Phase Ia/Ib first-in-human clinical trials. ADEL-Y01 is a novel monoclonal antibody therapy which targets the abnormal tau protein responsible for neuron death in the brain.3
Specifically, the drug is aimed to bind acetylated tau, inhibit its aggregation, and promote clearance, distinguishing it from existing therapies that are largely limited to symptomatic improvement in cognition or alertness. The following outlines the current clinical trial design conducted by Sanofi, a French biopharmaceutical company, in collaboration with South Korea-based ADEL:
- Part 1 – Single Ascending Dose
- Enrolling up to 40 healthy adults aged 18-65 divided into five groups of eight participants each (six receiving ADEL-Y01 and two receiving placebo)
- Participants receive a single intravenous dose of ADEL-Y01 or placebo
- Dose start at 2.5 mg/kg up to 100 mg/kg
- Safety, tolerability and pharmacokinetics are assessed over 12 weeks
- Part 2 – Multiple Ascending Dose
- Enrolling 33 adults aged 50-80 years with mild cognitive impairment due to AD
- Participants receive a total of six doses of ADEL-Y01 or placebo every two weeks (7.5 – 50 mg/kg)
- Safety, tolerability and pharmacokinetics are assessed over 22 weeks
The phase Ia/Ib trials aims to determine whether ADEL-Y01 is truly safe, tolerable, and effective in the body.3 This study represents the first evaluation of ADEL-Y01 in human subjects and provides critical insight into its effects on pathological tau.
Conclusion
By understanding the role of tau in neuron communication, targeted treatment strategies addressing underlying disease mechanisms can be developed. Though still in clinical trials, the development of ADEL-Y01 is a breakthrough as a potential cure for a common disease among the increasing aging population. It serves as a shift in Alzheimer’s disease research. Clinical evaluation is essentially in determining the drug’s safety and efficacy. Now, it is up to student pharmacists and pharmacists to keep our community updated and educated on future treatment strategies.
References
- National Institute on Aging. What is Alzheimer’s disease? NIH/NIA. Updated March 4, 2025. https://www.nia.nih.gov/health/alzheimers-and-dementia/what-alzheimers-disease.
- Medeiros R, Baglietto-Vargas D, LaFerla FM. The role of tau in Alzheimer’s disease and related disorders. CNS Neurosci Ther. 2011;17(5):514-524. doi:10.1111/j.1755-5949.2010.00177.x.
- Alzheimer’s Disease Expert Lab (ADEL), Inc. A Phase Ia/Ib, First-in-human (FIH) Study for Safety, Tolerability, Pharmacokinetics (PK), and Clinical Activity Evaluation of ADEL-Y01. ClinicalTrials.gov Identifier: NCT06247345. Last Update Posted November 18, 2025. https://clinicaltrials.gov/ct2/show/NCT06247345.
