Product Development Overview
iPierian’s initial drug development programs in its pipeline are for monoclonal antibodies to treat neurodegenerative diseases by addressing targets of the Tau protein and the Complement cascade of the immune system. The monoclonal antibody development programs evolve from iPierian’s proprietary iPSC technology for disease modeling – utilizing patient-derived cortical neurons, motor neurons, microglia, and astrocytes. These human disease models are used to discover and validate novel targets and molecules for diseases in neurodegeneration and neuroinflammation.
Targeting Tau Protein
In targeting of Tau protein, iPierian’s approach using iPSC technology offers the potential for a distinctive angle into the importance of the target in normal physiology and in specific patient populations. By studying the role of Tau in human cell-based models, the company aims to advance a novel therapeutic into the clinic for multiple tauopathies – such as Alzheimer’s disease, Frontotemporal Dementia, Progressive Supranuclear Palsy (PSP), and others.
Tau in Neurodegenerative Disease
The Tau protein functions to stabilize microtubules and is abundant in neurons in the central nervous system. Aberrantly modified forms of tau have been correlated with dementias such as Alzheimer’s disease (AD), Frontotemporal Dementia, PSP, and other tauopathies. Aberrant Tau accumulation correlates with the disease progression of dementia, in contrast to Amyloid which maximally deposits years prior to dementia and therefore may be too late to intervene against. Animal models of AD have recently suggested that Tau can spread from one neuron to another, transmitting pathological Tau and correlating with the progression of AD pathology in humans. It is possible that therapeutics which slow the spread of Tau may also slow the clinical course of AD and related tauopathies.
Targeting the Complement System
In targeting the Complement cascade in the innate immune system, iPierian is focused on using its proprietary iPSC models for targets that address the pathological role of inflammation in chronic neurodegeneration. In particular, therapeutics that can modulate the activity of glial cells may be able to slow or halt the progression of many acute and chronic neurological diseases.
Complement in Neurodegenerative Disease
The complement system consists of a family of distinct proteins that play a pivotal role in host defense against infection, as well facilitating phagocytosis by macrophages/microglia and promoting inflammation. Many inflammatory, autoimmune, and infectious diseases have been shown to be associated with excessive complement activity. Complement activation has also been associated with several neurodegenerative diseases – including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Genome wide association studies have identified polymorphisms in genes encoding components of the Complement pathway as risk factors for Alzheimer’s disease.