My Alzheimer's Journey
Part 134 - AbbVie ABBV-1758
Last Friday, I briefly discussed ABBV-1758, an Alzheimer’s therapy AbbVie acquired from Aliada Therapeutics in 2024. According to AbbVie, the secret sauce for ABBV-1758 is the novel delivery technology, known as MODEL (Modular Delivery).
I have fully researched ABBV-1758 and MODEL. It certainly seems to be a strong candidate for a game changing future AD therapy.
The MODEL drug delivery system was originally developed by scientists at Janssen (a division of Johnson & Johnson). Simultaneously, the development of an Alzheimer’s therapy candidate known as ALIA-1758 was underway at Janssen. In 2021, Aliada Therapeutics was co-founded by Johnson & Johnson and venture capital partners (RA Capital and Raven) to advance both the MODEL technology and ALIA-1758. Aliada had a licensing agreement for the MODEL technology. AbbVie acquired Aliada in late 2024.
ABBV-1758 is an amyloid beta antibody. It is designed to target pyroglutamyl amyloid beta-protein. In a future article, I will explain pyroglutamyl in detail. For our discussion of ABBV-1758, we only need to know that pyroglutamyl is a highly toxic (corrupted) form of the amyloid-beta peptide. Peptides are short chains of amino acids - the building blocks of proteins - that act as signaling molecules, influencing hormone regulation, tissue repair, muscle growth, and immune function.
These corrupted proteins are sticky and very difficult for the brain to naturally clean.
In a healthy brain, amyloid-beta proteins are created, used, and recycled. In an AD brain, the recycling function stops and the amyloid-beta proteins pile up.
Pyroglutamyl amyloid beta-protein is a major seeding component of the senile plaques found in the brains of patients with AD. The senile plaques are clumps that form and block communication between brain cells (neurons) causing them to eventually die. This is what leads to memory loss in AD patients.
The term “seeding” explains how AD spreads. When one seed forms, it forces all the regular proteins around it to also misfold and stick to it. Think of it as the snowball effect.
To summarize, pyroglutamyl amyloid beta-protein is the primary ingredient that starts the “clumping” process, making it one of the most dangerous players in the development of Alzheimer’s disease.
It now makes sense why ABBV-1758 targets pyroglutamyl amyloid beta-protein.
Since the United States is in the midst of a war with Iran, I will use a war analogy to explain the ideal process. MODEL is a regiment of highly trained ground troops deployed to the skull of a person with AD. These ground troops have water pistols loaded with ABBV-1758. They penetrate the BBB and squirt ABBV-1758 on the pyroglutamyl amloid beta-protein. This stops the clumping process and slows down the progression of AD.
In May 2024, Aliada (prior to their purchase by AbbVie) began a Phase 1 trial with a single-dose of ABBV-1758 (known as ALIA-1758 at that time) in healthy participants. It tested the safety, tolerability, and pharmacokinetics of intravenous or subcutaneous doses of ABBV-1785. The trial enrolled 53 people. According to clinicaltrials.gov, the study ended April 22, 2025. Results have not been posted.
AbbVie does not have any future ABBV-1785 clinical trials listed on their trial recruiting website. I will continue to monitor AbbVie for ABBV-1785 updates.
During my research for this article, I read an interview Pharmaceutical Executive conducted with John Dunlop, Aliada Therapeutics' Chief Scientific Officer. This interview was published June 12, 2024 - prior to AbbVie’s acquisition of Aliada.
Dr. Dunlop was asked, “Are you excited about the seemingly accelerating progress in the Alzheimer’s disease field in recent years?”
He responded, “I think there has been just tremendous progress in the Alzheimer’s disease space. Biomarkers now really make us very confident that subjects coming into trials already have evidence of amyloid pathology in the brain, because we can look at it through PET imaging and we can measure different beta-amyloid and tau species in the blood that are also correlated with those PET images. When you think back to the initial trials of some of the initial Aβ antibodies almost 30 years ago, about a third of the subjects who were enrolled in those trials didn’t actually have amyloid pathology in their brain, which we learned when they passed away. They had some other type of dementia, instead. This factor was diluting the potential to see a signal in a clinical trial. Now we can very definitively recruit subjects with Alzheimer’s disease, and we are very biomarker-enabled to track the progress of our therapeutics. So, we’re very excited to be starting our clinical program very soon.”
Dr. Dunlop’s perspective on Alzheimer’s disease research is encouraging. Let’s hope the research continues to accelerate in the next five to ten years.
My Alzheimer’s Journey does not offer paid subscriptions. Instead, we depend on subscriber donations to cover the cost of research and writing. Additionally, all donations support my direct and indirect Alzheimer’s treatment expenses. Thank you.
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