About us

Origin story

Amlogenyx is developing a novel protease therapy shown to reduce amyloid (Aβ42) accumulation in preclinical models of Alzheimer’s disease. Amyloid accumulation has been shown to predict progression of Alzheimer's disease, and treatment with monoclonal antibodies to reduce amyloid has been shown to potentially slow the disease but not stop or reverse it. There is a clear need for better treatment options. Dr. Alessandra d’Azzo, Ph.D., at St. Jude Children’s Research Hospital in Memphis identified a more potent method of degrading amyloid within neuronal cells that relies on the protective protein cathepsin A (PPCA)/neuraminidase (neu1) complex. Her early studies in murine models showed that deficient PPCA/neu1 enzyme complex caused extensive amyloid accumulation. She expanded on that discovery by showing that crossing a murine model that made excess PPCA enzyme with a murine model of severe Alzheimer’s disease could counteract amyloid accumulation. This provided the first evidence that providing PPCA enzyme could offer therapeutic benefit in Alzheimer’s disease.

Based on these results, Ultragenyx studied the effects of PPCA in vitro and showed it could potently degrade amyloid in various oligomeric and higher forms. Ultragenyx then worked with Dr. D'Azzo to develop an AAV9 gene therapy that can deliver supplemental PPCA enzyme to the brain and has shown a substantial reduction in Aβ42 accumulation in murine models of Alzheimer’s disease that exceeds that observed with monoclonal antibodies.

If gene therapy were to work for a large population like Alzheimer’s disease, it would have to be far cheaper than the multi-million dollar prices set for rare diseases. Ultragenyx has the technology with its Pinnacle PCL^™ platform to enable cost-effective, commercial scale AAV manufacturing that can support a large indication like Alzheimer’s disease.