Translational Neuroscience at inStem

The mission of the Centre for Brain Development and Repair (CBDR) is to understand the cellular, physiological and behavioural basis of developmental brain disorders, and to use this knowledge to test and devise novel therapies.

Disorders of the brain pose a major and growing health challenge to India. Our vision is to accelerate the discovery and delivery of effective therapeutics for these largely untreatable conditions. Although these are a disparate group of currently untreatable conditions that span the life-course from development through to ageing there are nonetheless common themes and needs. These include the recognition that key molecular mechanisms and biological processes are shared across many of these diseases indicating that discoveries in one disease group are likely to inform the other and vice versa.

Uniformly the unmet need is for an innovative combination of studying human disease biology and animal model for investigating the causes, consequences and ultimately treatment of these diseases. Critically this requires (1) a cadre of clinician-scientists who can both inform basic science as well as lead the underpinning clinical research necessary for translation of laboratory discoveries and (2) building INDIA based and led, deep phenotyped longitudinal disease cohorts that are well annotated.

Developing and integrating these human and infrastructural resources will establish a self-sustaining pipeline for both human disease biology-led discovery science as well as begin to enable precision medicine and targeted early phase clinical trials. Presently India does not have the comprehensive framework for meeting these twin needs. Our goal is to address this major gap in translational neuroscience by adopting a targeted and phased approach at the Centre for Brain Development and Repair (CBDR).

CBDR was established in 2013 with core support from inStem as well as generous support from the Shanta Wadhwani Centre for Cardiac and Neural Research and a grant from the Department of Biotechnology (DBT) entitled “Centre for Neurodevelopmental Synaptopathies” (CNS). This is an international collaborative partnership between inStem, NCBS and the University of Edinburgh. In this component the focus is on neurodevelopmental disorders, such as autism spectrum disorders and intellectual disabilities (ASD/ID) with a mission to establish discovery and delivery platforms based on human stem cells and rodent models to enable a transformative programme of work that pioneers an integrated and new approach to the understanding of brain disorders. The program works at multiple levels from synapse to cell to circuit to identify novel therapeutic targets and effective pre-clinical translational platforms. Crucially this approach targeting fundamental biological processes and establishing cross-cutting platforms means that these investments can be readily leveraged to other major groups of brain disorders.

Building from our core platforms, new partnerships have been established with the National Institute for Mental Health and Neurosciences (NIMHANs) to train a cohort of Indian clinician-neuroscientists necessary for the translation of laboratory discoveries to the clinic. Linked to this development, we have also expanded our scientific horizons to include neurodegenerative disorders beginning with inherited amyotrophic lateral sclerosis and fronto-temporal dementia.

Finally, the above programs serve as an ideal foundation for scaling our research in translational neuroscience to target adult neuropsychiatric disorders in the Indian context. Improved understanding - that recognizes these are complex disorders that result from poorly understood genetic and environmental interaction - requires the study of human cells, tissues and function from deeply-phenotyped cohorts exhibiting normal and pathological variation in cognitive function. We therefore propose to exploit and overlay the assay platforms developed at CBDR onto comprehensive fully-annotated “genes and tissues-to-clinic” longitudinal neuropsychiatric disease bio-registers in order to better understand and dissect (a) genetic-environment interaction in disease causation and (b cell-based assays on patient derived cell lines to model aspects of disease biology as well as establish drug discovery platforms. In summary, the long-term goal of this phase is to establish a sustained program of research to understand the development and mechanistic basis of common, debilitating neuropsychiatric disorders in the Indian population. This has led to a new initiative, the Accelerator Program for Discovery in Brain Disorders using Stem cells (ADBS), funded by a multi-centric grant to NIMHANS, inStem and NCBS and generous support from the Pratiksha Trust, bringing together researchers at inStem, NCBS and clinicians at NIMHANS.