Gene Therapy AM805 Aims to Reverse Alzheimer's by Degrading Amyloid

NOVATO, CA – March 16, 2026 – In a potential paradigm shift for Alzheimer's treatment, biotechnology firm Amlogenyx Inc. today announced highly positive preclinical results for AM805, an investigational gene therapy designed to directly degrade the toxic amyloid proteins that are a hallmark of the devastating neurodegenerative disease. The data, presented at the AD/PD™ 2026 International Conference on Alzheimer’s and Parkinson’s Diseases, suggest the one-time therapy can robustly clear amyloid from the brain, potentially offering a more powerful and durable solution than current treatments.

AM805 utilizes a novel catalytic approach that not only reduces the amyloid plaques found outside of brain cells but also, crucially, targets the amyloid building up inside neurons. This dual-action mechanism, which demonstrated amyloid reduction comparable to or exceeding that of approved antibody drugs in animal models, has ignited hope for a therapy that could halt or possibly even reverse disease progression.

“Despite clear biology implicating amyloid in Alzheimer’s... treatments that can halt, or possibly even reverse, disease progression have eluded researchers to date,” said Arjun Natesan, head of early R&D at Amlogenyx. “We are extremely pleased to present preclinical data demonstrating that AM805 can achieve robust amyloid reduction... underscoring its strong potential to prevent and treat this devastating and intractable disease.”

A New Weapon in the Amyloid War

The current generation of disease-modifying Alzheimer's drugs, such as lecanemab and donanemab, are monoclonal antibodies that function like a cleanup crew. They bind to and help clear existing amyloid plaques, slowing cognitive decline in patients with early-stage disease. While a major breakthrough, these therapies require regular intravenous infusions and come with risks, including brain swelling and microbleeds. They primarily slow the disease's march, rather than stopping it in its tracks.

AM805 represents a fundamentally different strategy. It is an AAV9 gene therapy—a disabled virus used as a delivery vehicle—that carries the genetic instructions for a potent lysosomal enzyme called protective protein cathepsin A (PPCA). Once delivered to the central nervous system, brain cells begin producing this enzyme, which acts as a biological incinerator, catalytically degrading amyloid peptides.

This approach addresses a key aspect of Alzheimer's pathology that many other therapies do not: the toxic accumulation of amyloid within the neuron. Lysosomes, the cell's waste-disposal organelles, become dysfunctional in Alzheimer's, allowing this internal buildup. By boosting the levels of the PPCA enzyme, AM805 aims to restore this critical waste-clearing function. The preclinical studies, a collaboration with St. Jude Children's Research Hospital, showed that this increased PPCA activity successfully lowered amyloid levels in both intracellular and extracellular compartments across multiple mouse models, even in advanced stages of the disease.

From Lab Bench to Bedside: The Long Road Ahead

While the data from mouse models and the demonstration of safe delivery in non-human primates are generating significant excitement, the journey from lab to clinic is long and fraught with challenges. The history of Alzheimer's research is littered with promising preclinical candidates that failed to translate into effective human treatments. Amlogenyx is now focused on the next critical step: submitting an Investigational New Drug (IND) application to the U.S. Food and Drug Administration, which it plans to do in 2027, to begin human trials.

Key questions remain that only human studies can answer. Will the AAV9 vector deliver the gene therapy to a sufficient number of brain cells to have a therapeutic effect in the much larger and more complex human brain? Will the therapy be safe over the long term, without triggering adverse immune responses? And most importantly, will the dramatic amyloid reduction seen in mice translate to a meaningful halt or reversal of cognitive decline in people?

However, the potential rewards are immense. As a one-time treatment, AM805 could eliminate the need for repeated infusions, a significant quality-of-life improvement for patients and their families. Its ability to target both internal and external amyloid offers a more comprehensive attack on the disease's core pathology, holding out the tantalizing possibility of not just slowing, but truly altering the course of Alzheimer's.

Ultragenyx's Big Bet on the Brain

The ambitious and costly development of AM805 is backed by the considerable resources of its parent company, Ultragenyx. Known primarily for developing therapies for rare and ultra-rare genetic diseases, Ultragenyx has made a clear strategic expansion into the highly competitive neurology space. This move is supported by a strong financial foundation, with projected revenues of over $640 million for 2025 and a stated goal of achieving profitability by 2027.

This financial stability allows the company to fund high-risk, high-reward programs like AM805. Ultragenyx's portfolio already includes several other gene therapies for neurological conditions, such as for Sanfilippo syndrome and Angelman syndrome, demonstrating a deep institutional commitment to and expertise in this cutting-edge therapeutic modality. The investment in Amlogenyx is not a speculative one-off but part of a broader corporate vision to tackle complex diseases of the central nervous system.

A Crowded Field of Hope and Innovation

AM805 does not enter the fray in a vacuum. The Alzheimer's pipeline is more vibrant than ever, with over 130 novel drugs in clinical trials. Competition in the gene therapy space is also heating up. Lexeo Therapeutics, for instance, is in early-stage trials with a therapy that delivers the protective APOE2 gene, which is associated with a lower risk of developing Alzheimer's. Other approaches are focused on using gene therapy to boost levels of neuroprotective factors like BDNF or to silence the production of the tau protein, another key culprit in the disease.

Yet, AM805’s unique mechanism—unleashing a natural enzyme to catalytically destroy amyloid—sets it apart. It represents a direct and aggressive assault on the protein widely believed to initiate the disease cascade. As Amlogenyx prepares for the pivotal transition into human trials, the medical world watches with cautious optimism, hopeful that this novel enzymatic approach could one day turn the tide against the devastating progression of Alzheimer's disease.