Flagship Projects

Introduction

India is witnessing a rapid increase in its older adult population, accompanied by improvements in life expectancy. However, many older adults continue to face chronic illnesses, declining physical function, mental health concerns, financial insecurity, inadequate access to healthcare, and limited social support. Yet, despite these challenges, many continue to lead fulfilling, independent, and resilient lives.

“Why do some older adults thrive while others struggle under similar circumstances?” This fundamental question lies at the heart of the ELITE study. Using a mixed-methods approach, the study seeks to identify the factors that enable healthy and successful ageing beyond medical care by examining the multidimensional determinants of quality of life alongside older adults’ lived experiences, coping strategies, resilience, and perceptions of ageing in urban Bengaluru.

Additionally, the study will explore microbiome patterns associated with better quality of life and longevity, laying the foundation for future research on the gut–health–longevity axis and potential interventions to promote healthy ageing.

The findings will generate evidence on the facilitators and barriers to healthy ageing at the individual, family, and community levels, informing policies and interventions to support healthy and active ageing in India.

Investigators

Dr. Yogesh Shouche, Dr. Lavanya Garady (PIs)

Dr. Arun N, Dr. Ahalya P Gopi (Co-PIs)

Introduction

Cardiovascular Diseases (CVDs) are considered as one of the leading causes of death, estimating around 17.9 million deaths annually in the world. Amongst these, more than four-fifths of the deaths are attributed to heart attack and stroke. Despite having knowledge of conventional risk factors and efforts to avert them, yet there has been a gradual increase in the incidence of these diseases among Indians. According to GBD (Global Burden of diseases) their prevalence has doubled in India since 1990. Regardless of the growing need to address this problem, there is currently lack of availability of a heart attack and stroke risk predictability calculator tailored to the Indian population.

The decade-long SKAN-HASP study (Heart Attack and Stroke Predictability Study) is divided into multiple phases and seeks to create a dynamic risk calculator merging principles from evidence-based medicine, Yoga, Ayurveda and certain lifestyle modifications. While the study focuses on developing a predictability calculator, it is holistically designed to gain insights into several causal pathways. Several studies have been planned within the large sample size of 3.5 lakh population. The study is designed to cover a spectrum of geo cultural variability and socio-economic strata of Indian population.

Although the study has a predominant prospective design, numerous smaller studies within the larger ambit of longitudinal study have been planned to have robustness and generalizability. (Case-control design, case cohort design, nested case control study etc). HASP study additionally delves into the deep dive focused under researched areas such as stem cells, gut microbiome and genetic components to better understand some of the lesser-known mechanisms in both stroke and CVDs.

All the learnings emerging from HASP study intends to help doctors and other health care providers select effective therapies and aid individuals with reducing their susceptibility to stroke and CVDs.

Collaborators

The study divides cohorts between Narayana Health / Mazumdar Shaw Medical Foundation, NIMHANS, SKAN-RT, Foundation for Revitalization of Local Health Traditions (Trans-Disciplinary University – TDU).

Investigators

Dr. Yogesh Shouche (PI)

Dr. Lavanya Garady, Dr. Arun N, Dr. Somak Kumar Chowdhury (Co-PIs)

Project Overview

The partner institutes for this project are Hirabai Cowasji Jehangir Medical Research Institute (HCJMRI), Pune & KMCH Research Foundation, Coimbatore. Type 1 diabetes mellitus (T1DM) is an auto-immune disorder that occurs in a genetically susceptible individual due to certain environmental triggers resulting in the destruction of insulin-secreting pancreatic cells. According to a recent report, India is ranked 59th in the world with an incidence of 4.2 T1DM cases per 100,000 populations (IDF, 2021).

HCJMRI

Hundred and thirty-one children diagnosed with T1DM and 79 healthy children have been enrolled by HCJMRI as participants for the study. Data entry has been completed for all enrolled participants, while data compilation is in process. Additionally, blood and stool samples for a total of 210 children have been collected. 210 stool samples have been submitted to SKAN Research Trust for microbiome analysis. Enrolment of 20 subjects with T1DM and 1 healthy control as subjects is yet to be done. Researchers from KMCH Research Foundation, Coimbatore have been provided training on data collection procedure and administration of cognition testing. More than 50% data collection has been achieved.

KMCH Research Foundation

120 children with type 1 diabetes were pre-identified and received oral consent from both the children and their parents by KMCH Research Foundation for participation in the study. The written informed consent will be obtained during enrolment and sample collection. The team traveled to Jehangir Medical Research Institute to receive training in performing the BKT test for cognitive testing. Further, it will be ensured that all procedures including data collection, blood anthropometry, and sample collection are being performed in a coordinated manner. Samples collection has started after performing the BKT test. Until now, 35 samples have been collected from children with T1DM condition. The process of identifying the age and sex-matched healthy controls for this study is underway. Data and sample collection has been completed for 35 children diagnosed with T1DM.

Project Overview

The partner institute for this project is National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru. This project aims to assess any changes in the microbiome starting from the hospital admission till acute antipsychotic therapy administered as part of standard medical procedure.

Project Progress

The project is currently in the second month and progressing. Advertisement and Recruitment of staff nurse for the project has been done. NIMHANS has finalized the questionnaire for the alcohol and tobacco use in the study with the guidance of Dr. Jayant Mahadevan, Centre for Addiction medicine, NIMHANS. Technical training has been provided to Ms. Harshitha (the nurse recruited for the project work) about using various assessment tools like brief psychiatric rating scale etc. Clinical assessment of at least 15 patients included in the pilot study was conducted by Ms. Harshitha and was discussed with the team on regular basis.

The inputs received from the team were implemented to improve the clinical assessment. NIMHANS has started patient recruitment process since the past 3 weeks, looking for cases which match the inclusion criteria in the psychiatry wards, with the help of senior residents and ward staff on daily basis. Around 55 admitted patients were assessed – none of them met the criteria set by NIMHANS, which implies either the patients were under antipsychotic medications / antibiotics, or were elderly, or having gastro-intestinal illnesses or thyroid dysfunctions. Also, NIMHANS found difficulty in recruiting the patients as most individuals are on psychotropic medications (patients on antidepressants/ mood stabilisers).

Partner Institute

St John’s Medical College & Hospital/ St John’s Research Institute/ St John’s Geriatric Centre.

The “SOHAM Cohort Study” emerges against the backdrop of the global imperative of Healthy Ageing, a concern shared by India, where the absence of precise tools to identify “healthy ageing” individuals impedes the understanding of factors contributing to chronic diseases in this demographic. With India’s elderly population projected to grow significantly, reaching 12% by 2025 and nearly 20% by 2050, the need for a comprehensive, locally adapted tool covering all domains and biomarkers to identify “Healthy Ageing” is paramount.

This initiative aims to address this gap and contribute to the development of effective prevention strategies, ultimately reducing avoidable ill health in the ageing population. Over the past year, significant progress has been made in the project. The conceptualization and planning of the study, including defining its scope, objectives, and methodology, have been completed.

The design of the “SOHAM Study” has been finalized, comprising two parts: the drafting, enriching, refining and validating of the Healthy Aging Tool – India (HAT-I) in Part 1, and the longitudinal follow-up of a large number of subjects assessed with the HAT-I tool for aging trajectory analysis in Part 2. Ethical clearance for the research project has been obtained, and a diverse team of professionals have been assembled through staff recruitment. The team has undergone intensive training to ensure data accuracy and competence. The project has achieved several milestones, including the completion of drafting, enrichment, and refinement components of the study. The qualitative study has been submitted as a manuscript, and the recruitment process for the validation study has been initiated.

Partner Institute

National Institute of Mental Health and Neurosciences.

The study aims to provide a better understanding of the complex interplay of genetic, molecular, and environmental interactions as causation factors for both young and late onset Parkinson’s Disease (PD). Results from this study will not only help in examining the different causation factors for both forms of PD but also aid in developing improved prognostic measures against the disease.

To achieve the study objectives, longitudinal follow up of PD patients, with detailed neurological and neuropsychological evaluation will be undertaken. In parallel, studies on mouse models will aid in understanding the molecular underpinnings of motor and non-motor symptoms of PD. So far, 180 samples from the total target of 1000 have been collected and processed for DNA extraction. Genome Wide Association Study (GWAS) analysis has been completed for 98 of these samples and another 96 samples are currently being processed for NGS and GWAS.

The clinical components of the YLOPD study are managed by NIMHANS. The broad objectives of this cohort are to gather data on clinical and genetic. neuroimaging and neurophysiological characterization of a large Indian young onset PD (YOPD, age at onset ≤45 years) and late onset PD (LOPD; age at onset greater than 45 years) and to identify probable biomarkers for early detection, monitoring progression (over 5 years), prognostication of disease and response to different medical and surgical therapeutic strategies.

Partner Institute

The partner institute for this project is the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru and Narayan Hospitals (NH).

This is a large cohort study aimed at understanding the natural history of stroke employing a mixed cohort study design (Retrospective-Prospective cohort study). This will be conducted in Mulbagal taluka of Kolara district and select urban wards of Bengaluru city. Sampling strategy has been finalized. The estimated sample size of 2 lakh people aged 30 years and above will be followed up for a period of 4 years as ‘stroke-free cohort’, stratified based on a set of risk factors such as obesity, stress, substance use, and diet/physical activity, other NCDs cohorts amongst the eligible population of ~4 lakh. After the first-ever incidence of stroke among participants, a new cohort named ‘stroke cohort’ will be formed utilizing a prospective cohort study design consisting of an expected case load of ~750 cases over 3 years.

The study also adopts the Quasi Experimental Pre-Post intervention study design to a sample of 255 stroke cases to study the effectiveness of a Comprehensive Acute Stroke CAre moDEl (CASCADE model) developed to improve preparedness, management of stroke, ensuring improved survival, reduced disability, and enhanced quality of life of stroke patients. Monitoring protocol and format has been developed through workshop. Clinical Trial Registry India (CTRI) registration number has been obtained for this study. Specific achievements are Stroke-free, Stroke and Hospital preparedness questionnaire near final, protocols finalized and approved by the Expert advisory group. The approvals of IEC for all the amendments in the protocol were obtained.

Partner Institute

Indian Institute of Technology Roorkee and NIMHANS.

A major lack of understanding about the pathophysiology of bipolar disorder (BD) poses the greatest challenge in the development of highly efficacious treatments against this disease. Furthermore, symptoms of BD have considerable overlap with other neuropsychiatric diseases (like anxiety, depression, mania etc.) complicating existing symptom-based diagnosis. Although miRNA, proteomic and metabolic profiling of BD patients has been undertaken as diagnostic tools for BD, the role of exosomes has not been explored in a similar vein.

This project aims to assess whether biochemical changes in exosomes of patients with BD and other allied neurological disorders (like anxiety, depression, mania etc.) can induce neurotoxicity in neuronal cell cultures. Further, based on the aforementioned situation of limited therapeutic options, a safer alternative to fight these neurological disorders is envisioned as a part of the study. To achieve the same, exploring nutraceuticals/dietary supplements has been targeted in this study, as these agents can act on multiple targets simultaneously.

Studies on neuronal cell lines treated with reserpine and glutamine were conducted, and these identified different biomarkers expressed during cellular stress. Thus, an in-vitro neuronal cell-based BD model was developed, that is currently being validated for wider applicability. Data thus far reveal that co-treatment with these drugs leads to BD like symptoms in neuronal cell lines. Further, an in-vitro screening model for testing the potential of certain nutraceuticals such as honey and an ayurvedic polyherbal formulation for the prevention/ management of BD has been developed.

Currently the study is in progress to understand its underlying mechanism of action. Another achievement of the project has been the revelation that serum constitutes of BD patients impact the normal functioning of neuronal cell cultures in-vitro.

Partner Institute

Narayana Health and NIMHANS

Stroke causes neuro-restoration that remains variable and treatment of stroke-caused infarct and penumbra is challenging. Standard stroke care includes thrombolysis, mechanical thrombectomy, decompressive craniectomy if indicated, and early rehabilitation. In addition to above treatments, novel therapeutic modalities include stem cell therapy, neuromodulation, brain-machine interface, robotic rehabilitation and multimodal treatments. Stem Cell-Based Stroke Management Program includes collaboration between Mazumdar Shaw Medical Foundation (MSMF) and Narayana Institute of Neurosciences, MSMC under Narayana Health (NH), a program for the clinical application of stem cell treatment in stroke survivors.

Aim

To establish, identify markers of plasticity/recovery and modify stem cell treatment protocols to enhance functional recovery with augmentative techniques and assess the effects of these adjuncts on overall patient outcomes.

In last year, Advanced Stroke Monitoring Lab with Functional Transcranial Doppler, Transcranial Magnetic Stimulation (TMS), Functional EEG, Quantitative Motion Analysis, Computerized Cognitive Assessment to be used as an advanced stroke diagnostics facility. TMS and Transcranial Doppler device testing on healthy controls has been initiated. BSL2 Facility has been expanded and functional. cGMP facility has been initiated and is in progress in consultation with a regulatory expert with Standard operating protocols being developed. The project has been divided into 5 phases for stroke, phases 1A to 1C will focus on discerning the effects of hyperbaric oxygen (HBOT), augmented reality, and robotic rehabilitation in different phases of stroke recovery. Phase 2A and 2B will focus on the effects of stem cells and adjuncts on recovery from stroke. The in vitro studies to see effect of HBOT on viability, proliferation, and molecular profile in human astrocytes (HA), glioma cells (U251) are being assessed along with Bone-marrow derived mesenchymal stem cell line (Hs_5) in future. Project milestones achieved are IEC Approval and patient recruitment for the HBOT and robotic rehabilitation trials. Manuscripts under preparation; use of adjunctive hyperbaric oxygen and peripheral magnetic stimulation (device procured from SKAN grant), and functional transcranial Doppler in healthy controls.

The Quadram Institute Bioscience (QIB) and SKAN Research Trust have forged a Comprehensive Partnership Agreement on May 19, 2023, to jointly address gut health and pioneer gut-based therapies for combating ageing and neurological diseases. QIB, a prominent UK national science entity, is dedicated to advancing healthier lives through innovations in gut health, microbiology, and food sciences.

The collaboration outlines various key areas of cooperation, including joint research projects in the UK and India to develop microbiome-based products for human health, technology transfer from QIB to SKAN, training of SKAN research scientists at QIB, and the study of large Indian population cohorts to formulate therapies tailored to India’s unique health challenges (ageing and neurological diseases). A specific research project, “Development of Phage Therapies to Alleviate Symptoms of Parkinson’s Disease”, has been identified under this collaboration. Dr Arjan Narbad from QIB and Dr Yogesh Shouche from SKAN will serve as principal investigators for this endeavour.

The project aims to investigate the role of sulphate reducing bacteria (SRB) in the development of Parkinson’s Disease (PD) and explore phage therapy as a targeted strategy for controlling SRB in the gut to potentially alleviate PD symptoms. Furthermore, three SKAN research scientists will undergo a year-long training program at QIB, supervised by Dr Arjan Narbad.

SKAN will cover the training fees and consumables cost amounting to GBP 20,000 annually for each scientist. The training is expected to commence by the end of 2023. The overarching objectives of the research project involve conducting a comparative microbiome analysis of PD patients and healthy individuals, isolating and characterizing SRB and SRB-specific bacteriophages, and exploring the biocontrol of SRBs using phage therapy. The collaboration between QIB and SKAN holds promise for advancing scientific understanding and potential therapeutic interventions in the critical field of gut health and neurological diseases.

Introduction

SKAN Research Trust (SKAN RT), and the UK-based Wellcome-MRC Cambridge Stem Cell Institute (CSCI), executed a series of partnership agreements on 6 September 2023 in Cambridge to further accelerate stem cell studies in SKAN and India. SKAN – CSCI Consultancy Agreements-SKAN will upgrade its stem cell and bioinformatics facilities through inputs from CSCI and receive active assistance from CSCI to set up the SKAN Stem Cell Centre of Excellence. SKAN – CSCI Joint Study- Dr Jyoti Nangalia, Group Leader at the Wellcome-MRC Stem Cell Institute and Wellcome Sanger Institute, will be the Principal Investigator of the first SKAN – CSCI joint study on “The genomic landscape of neurodegenerative diseases of ageing in an Indian cohort”. The joint project will be carried out on Indian cohorts, which will also create opportunities. During this period, SKAN researchers will be trained in top-of-the-line technologies at CSCI.

Objectives and Background of the Study

Cells in the human body accumulates somatic mutations with age and are also affected by intrinsic and extrinsic factors. Once acquired, these mutations are passed from parent cells to daughter cells in dividing tissues, accumulated at the latter parts of life. Many of these mutations result in a single cell dividing into an uncontrollable clonal expansion leading to cancer. Moreover, recent data suggest that somatic mutations also drive a multitude of non-cancerous diseases. These clones result in loss of resilience and susceptibility to disease upon ageing. How these clones trigger different disease, and to what extent their growth is modified by factors such as environmental exposures and genetic background/ethnicity, we can begin to understand how to modulate these clones to reduce susceptibility to disease. The joint project aims to characterise the role of these somatic mutations and clonal expansions in Indian patients suffering from aging related neurodegenerative disorders.