iPierian of South San Francisco uses its knowledge and experience with developing iPS cells to discover drug targets for development of antibody-based therapeutics to treat neurodegenerative diseases.
The company builds disease models by reprogramming biopsy-derived fibroblasts from patients with neurodegenerative diseases, then reprograms the cells into iPSCs. These cells are then differentiated into functional disease-relevant cells including cortical neurons, motor neurons, microglia, and astrocytes. Grown together in petri dishes, pathophysiological and functionally differentiated disease models emerge.
“Technology is beginning to advance such that some researchers can now avoid the stem cell stage and go directly to a cell lineage such as a neuron,” Nancy Stagliano, Ph.D., CEO of iPierian, said. “The breadth of the field is driven by having an iPS cell that can be differentiated into multiple cells. The iPS cells serve as building blocks for forming a neuron, astrocyte, or microglial cell; each protocol for differentiation is different.”
“With neurodegenerative diseases,” she added, unlike diseases such as cancer, “it is difficult if not impossible to get samples while a patient is alive.” This has seriously hindered the development of disease-relevant models. But now, she said, “We can take fibroblasts from, for example, Alzheimer’s disease (AD) patients, and make them into a variety of brain cells.”
Having spent years at Ipierian getting the protocols for these models worked out, she says, “We have been excited in the changes and differences in cortical neurons from AD patients, compared to iPS cells from normal individuals.”
And, she noted, the company’s models have confirmed their lead drug candidate choices. “Our models in a dish exhibit significant changes in the amount and form of tau protein, confirming differences in the protein in AD models compared to normal neurons.” She further noted that the company has found a soluble form of the protein that makes an ideal drug target candidate.
Currently, she said, the company’s two programs, its anti-tau antibody program and complement protein program, “are entering animal studies. We are putting them into rat and mouse models of disease then we will be in the clinic in 2014 for both programs and hope to enter Phase I later that year.
“Our recent insights derived from human iPS cells have encouraged us to quickly move our Tau and Complement programs forward. iPierian’s patient-derived models of neurodegeneration and neuroinflammation are allowing us to realize the promise of iPSC technology in a very product-oriented way,” Dr. Stagliano noted.
While stem cells may not immediately provide therapies for human diseases, their use as models in drug discovery has given them an immediate purpose in life. As more models are developed that can accurately model neurodegenerative changes, more novel therapies may be discovered.