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Research Highlights

Anand et al, Neurology India 1999, 2002, has described the three differentially expressed gene transcripts helpful in discriminating the two allelic forms of the disease i.e. DMD and BMD with potential for future molecular diagnostic application. This was recommended for patent by the Department of Biotechnology, New Delhi. Later, Ambati and Anand, Nature Medicine 2003 and 2004, also described the first transgenic animal model of age related macular degeneration (AMD) in CCL 2-/- and CCR 2 -/- mice, not only as a tool for studying the unification of inflammatory paradigm central to pathogensis of AMD and Alzheimer’s disease (AD), but also the pluripotency of stem cells and validating novel therapies. Monika et al described that PARK 2 mutations lead to Parkinsonism in India(Journal of Neurology, Neurosurgey and Psychiatry 2009; Sept 3 10.1136/jnnp.2008.157255). Saraf, Anand and Prabhakar described the antiamnesic effects of Brahmi using series of amnesic agents in mouse model of memory. Pal et alNeurology India, 2000 described the relationship of phenylthreo carbamide (PTC) with Epilepsy in Indian patients.

Significant Ongoing Research Activities

The laser injured retina mouse model has been developed using 600mW, 200ms and 70 micron laser spots underlying the retina. This is the first model developed in the country. Ongoing project seeks to repair this damage by implanting various sources of stem cells into this model and study their migration. A middle cerebral artery occlusion (MCAO) stroke mouse model is being currently standardized, and attempts are ongoing to rescue the neuronal damage in the ischemic penumbra by herbs and synthetic analogs. Bacopa Monniera has been tested for its antiamnesic effects in reversing drug and stroke induced amnesia in mice. The abeta induced Alzheimer’s disease mouse model has been established in the lab along with MCAO induced retinal ischemia mouse model which will further supplement our resources of battery of animal models. These will be used to screen additional molecules and biotherapeutics for preclinical evaluation including those derived from endurance exercises and mind body interventions. The emerging behavioral data is very encouraging and the molecular pathway is being mapped. The screening of CCl 2, VEGF and CCR 2 mutations in the patients of AMD and ALS is being carried out.

Research Goals for Next Fifteen Years

With the recognition of lab by Quality Council of India, it is envisaged to create intellectual environment permissive for acquiring Neuroscience leadership by a) mapping the key molecular mechanisms of neuronal regeneration and study their trafficking through invitro and invivo approaches b) to identify new targets for memory enhancement and delineate the mechanism of action of Bacopa Monniera in alleviating amnesia c) to identify the mechanism of action of various Yoga protocols for advancing our knowledge of untreatable diseases and wellness

A four-pronged approach is being adopted to visualize these research goals for the next fifteen years. Generation of mouse models for understanding the mechanism of neurodegeneration and testing the potential of stem cell implantation, with emphasis on utilizing neuroectodermally derived retina as a window to understand CNS plasticity; Genetic screening of Amyotrophic lateral sclerosis and Age related Macular degeneration to identify novel markers as tools for molecular diagnosis; Expression profiling of invitro differentiated stem cells derived from various sources such as bone marrow and ciliary epithelium into functionally viable neurons and test their integration into several animal models

We aspire to create an infrastructure that is compartmentalized into three physically distinct units to accommodate the growing number of PhD trainees, namely Memory lab housing the water maze and a laser instrument, Neural cell culture facility cum a human genetic screening lab and mind-body intervention unit

Animal Model of AMD and Human Validation

Dr Anand et al described the transgenic animal model of Age Related Macular Degeneration (AMD) in CCl 2-/- and CCr 2-/- mice (Nature Medicine 2003 and 2004){citation 639}. This set him to develop understanding of the mechanisms of cell survival and related markers in degenerative disorders after he returned home (Home coming, Ann Neuro 2017). For this, he set up a Quality Assurance based Research Lab in PGIMER (GLP compliant) which he developed in 5-6 years, exclusively from extramural funds, including MPLADS  (https://www.youtube.com/watch?v=FJatmJM8KtI)-ASK FOR PASSWORDS

As a logical follow up, Dr. Anand collaborated with Opthalmologists to screen Ccl2 and CCr2 SNPs/biomarkers by recruiting Indian AMD patients. This data supported the macrophage scavenging impairment theory in AMD (DAE YRSA AwardDST grant), earlier postulated in abovesaid Nature Medicine paper (PLoS One, 2012 {citation 25}, 2013(Cited in PUBLIC HEALTH) Curr Neuro Res {citation 19}, 2012, DNA cell Biology, 2012{citation 20, 1 cited in NATURE} and Gene, 2013{citation 16}), paving way for investigating additional missing links in Genetics of AMD from India (SLC 16A8, IER 3 etc) (Front Ageing Neurosci 2016){DBT funded}. A POC device and several patent applications are under active consideration based on these studies. The 27 MLPA based Neurogenetic tests launched by him for poor patients, with implications for female carriers (Ann Neuros 2016), included AMD, with amission to Internationalise the service. He is also on a mission to examine the efficacy of lifestyle intervention (Yoga and Naturopathy) in the conversion of dry AMD into wet AMD, MCI into AD, TIA into Stroke or Pre-cancer states into fully blown Cancers.

Degeneration and Neurovascular Network

Dr Anand and his team have been actively searching for new biomarkers of disease prediction, cell survival and burden, utilising statistical (PLOS one, 2018) and molecular tools, analyzing CSF and blood from various Neurodegenerative disorders like PD, ALS and AMD phenotypes (J Neurol Sci 2012). The ICMR funded project revealed elevated levels of VEGF, s-flt and CCl2 (and SNPs) in ALS patients postulating these to be involved in extending their mean survival time (PLoS One, 2012, Curr Neuro Res, 2012, J of Neuro, 2011)and may predict survival through patient CSF based invitro assay (ICMR funded). This discovery was also featured in ALSTD https://www.youtube.com/watch?v=KQ4cwkq7qEU

A frontline JNNP editorial has profiled the Dr Anand’s work on PARK 2 mutations (JNNP 2010). Another recently completed human study examined the effect of dystrophin gene in cognitive deficits among DMD/BMD patients (DAE funded)(in communication)

Can Stem Cells be useful in Retinal/CNS regeneration and function?

Dr Anand and his team established animal models of neuronal/retinal injury so that not only the herbal extracts but also various sources of stem cells could be compared with current therapies to generate molecular and neurobehavioral data on comparative effectiveness (Psychopharmacology 2008, {citation 48}). These animal models can be used by Indian and SAARC industries for drug development, biotherapeutic screening, skill development and toxicity testing as an International resource, given its Quality assurance program.

Following the leads, Dr. Anand, therefore, tested the role of enriched lineage negative BMSCs in the laser injured mouse retina and described its migration to the damaged site in a dose dependent manner with superior mobilization by Intravenous(IV) route. This was also tested in the PPA & NMDA induced RGC injury mouse model (DST, ICMR funded, Mol Cell Biochem, 2017, J Cell Biochem 2016). Dr Anand and his team have demonstrated that BMSCs survive upto 21 days post IV transplantation by the intravenous route (Stem cell Dev (PGI faculty award), 2012 {citation 20}and those derived from human cord derived lineage stem cells rescue memory deficits by upregulation of BDNF and CREB (Behav Brain Res 2015){DBT funded}. A patent application has been filed in Sept, 2019Some of these discoveries are being followed up and being examined via Yoga based intervention in healthy volunteers by intervention of Common AYUSH Yoga protocol(SATYAM-DST funded)

Parallel cell culture analysis revealed that the Jagged, Notch and Wnt are directly involved in formation of neurospheres at 6 days after culture of CE cells (derived from aborted fetuses)(ICMR funded study; Curr Neuro Res 2013, in collaboration with Iqbal Ahmad, UNMC, Omaha). Dr Anand is now compiling data in order to compare the regeneration promoting effects of these cells vs hUCB derived Lineage neg cells which were sub-retinally delivered in laser injured retina by analyzing ERG changes (DST funded) as well in animal model of Abeta induced memory loss (DBT funded)

Multinational Thought Leadership

Continuing his focus on Neurodegenerative Disorders, a frontline international review of multinational authors, led by Dr Anand, was published in Journal of Alzheimer’s Disease (AD) highlighting the roadblocks and solutions by advocating a multidisciplinary approach by use of Quality Assurance approach (J Alzheimers Dis. 2015:47,4: 815-843)because most of the Phase 3 AD clinical trials have failed. Many other multinational author publications have been profiled below as evidence of his capacity for team work and related writing assignments.

Modern Evidence for Traditional Medicine

In absence of success of clinical trials for AD, Dr. Anand and his team experimented with Brahmi (B. monniera) which reversed memory loss via CREB pathway using a series of amnesic agents, Morris water maze and neurochemical analysis (ICMR Award, editorial Mint June 2, 2015 ‘Memory and Ageing Brain’) (Psychopharmacology 2008, Neuroscience 2009), Behavioral Brain Research 2008, Pharmacol Biochem Behav 2010). He guided the development ofNano Bacopa formulation for overcoming blood brain barrier (in collaboration under Institute MOU, CSIR fellow). The results from dose dependent effect of Allium Cepa in recovery of mouse PPA injury are also being compiled (AYUSH funded and on a Institute MOU) in an effort to explore alternative therapies for retinal diseases. The mission to establish research based Integrated healthcare system is underway where comparative data between treatment outcomes between various pathies can be analysed for patient centered cost effective translation(http://www.tribuneindia.com/news/comment/should-pivot-of-nmc-be-patients-or-doctors/536261.html)

Quality First

In 2014 & 2016 Dr Anand’s Lab became the first research facility in the country to be recognized by Quality Council of India for broadening the purview of GLP for basic research investigations, digitization and community outreach.

Next 20 Years

A series of longitudinal Yoga based research projects are underway, including recent completion of NMB (Niyantrit Madhumeh Bharat), utilizing the knowledge, skills and expertise gained from animal models discussed above (Int Med Int 2016, 2017, Ann Neuros 2016). These are being implemented in order to test whether various markers and genes, which have been found to be involved in cell survival mechanisms are activated by Mind body techniques and Yogic exercises (SATYAM, DST funded). This is being developed in collaboration with S-VYASA, SSIAR, Patanjali Yogpeeth and patient organisations like IAMD, Solan and MDCRC, Coimbatore for effective communication and translation. (https://www.youtube.com/watch?v=HMbF_FQkjDs). Such provocative studies include the effect of Yoga protocols in prisoners and its efficacy in high altitude related acclimatization serving to examine the mechanisms using established animal models.

The recently launched Yoga project seeks to discover the markers of stem cell mobilization in Yoga practitioners, sampling blood at various time points. Preliminary and unpublished data at 1 month, from recruitment of IYD 2016 yoga volunteers, at the time of PM’s visit to Chandigarh, shows remarkable reduction in LDL and BMI with concomitant increase in HDL and cognitive processing, analysed by Trail A and B test. The results are under communication. Similarly, as Convener of North Zone of NMB program, led by Dr R Nagarathna (S-VYASA), the results of benefits of yoga intervention in conversion of Prediabetes into Diabetes (and related cognitive and perceived stress improvement) are being communicated. He has recently been invited to lead UGC’s ODL program of SVYASA.

Transforming Policy and Scientific Communication through Annals of Neurosciences & Integrative Medicine International

After taking over as the Editor of Annals of Neurosciences (the official Journal of Indian academy of Neurosciences) in Feb 2009, the Journal was revamped with continuous efforts. This has resulted in increased readership, annual subscriptions catalyzing the partnership of Indian Academy of Neurosciences (IAN)with Karger, Switzerland who published it worldwide until 2018. The Journal is now indexed in PUBMED and also being considered for impact factor. Dr Anand has also shaped the development of Integrative Medicine International for advocating Integrative healthcare by global advocacy and facilitated a new International partnership of Annals of Neurosciences with SAGE publishers. He has recently been invited to head a Journal in Intergative Medicine.

Societal Impact of Community Outreach

Dr Anand and his team have recently released a special supplement of ‘Magical Broom’(www.annalsofneurosciences.org) and “Magical Broom returns’ for health promotion among kids by use of public health initiatives, profiling the completion of 230 weeks or 460 hours of continuous Clean India activities voluntarily carried out by his Research lab in Chandigarh @ 2 hrs every week(https://swachhbharat.mygov.in/user/907433). This has instilled teamsmanship in research group and a spirit of community service, earning an appreciation by Prime Minister, Sh Narendra Modi(https://www.youtube.com/results?search_query=neuroscience+research +lab+chandigarh)and also by Ministry of Science and Technology (at IISF). Dr Anand has also been a resource person for scientific conceptualization and analysis of data generated from Joshi Foundation’s Mega health checkup camps, advocating the concept of Integrated healthcare. He continuously organizes health promotive activities like Yoga workshops in the city and regularly ideates for several Yoga schools and national educational policy framework.