Tuesday, August 4, 2015

Personalized Medicine: Where do we stand today?

With major advancements in diagnostic and therapeutic modalities, we are progressing towards an era where each individual gets treatment specifically for the disease in him.

Ten years ago, if a person walked into any hospital in India with a disease, the chances of getting diagnosed and treated by a set of arbitrary protocols were extremely high. The diagnostic tests were meant to confirm the etiology and determine the severity of illnesses. The treatment strategies were meant to address diseases as issues at a social tier. Gone are the days of conventional management tactics and regimens. Today, we are fortunate to avail the benefits of evidence based and personalized medicine. Diagnostic methods investigate beyond simple identification of illness at the generic level. Analysis of a disease to decipher the specificities to genomic level in a particular individual is the focus of diagnosis these days so that therapies can be tailored to address the problem right at its crux.

Skala et al from Vanderbilt University showed promising results of growing organoids in a petri dish from tumor cells harvested from patients to simulate the actual tumor. Fluorescence based quantitative optical imaging was used to measure NADH and FAD in 3D tumors in dish to analyze the drop in cellular metabolic level with each chemotherapeutic agent. This helps to identify drug sensitivity and resistance within 48 hours of culturing the cells, well before the actual treatment is started in patients. Researchers and clinicians in The Institute of Cancer Research and The Royal Marsden Hospital in London used the cutting edge 3D printing technology to “print” phantom tumor models of individual patients and used this to guide them in molecular radiotherapy and fine tuning the radiation dosage. We have grown past conventional radiotherapy too. The Proton Therapy with better tumor targeting has been boasting good recovery with least adverse effects of irradiation in Head and Neck, chest and abdominal tumors over these years in Prague prompting more centers in UK to utilize this technique by 2017. In United States, the Federal Government has undertaken a $215m Precision Medicine Initiative , a bold enterprise coordinated by National Institutes of Health (NIH) to comprehend diseases to the extent of customizing discrete preventive and therapeutic strategies. The initiative proposes near- term focus on cancers and long- term focus on a wider range of diseases.

In India, the disciplines of Basic Science research, Molecular Biology, Genomics, Bioinformatics are being brought together harmoniously by Government and Corporate resources. Council for Scientific and Industrial Research (CSIR) mediates the Indian Genome Variation (IGV) multi centric project to bring to light Single Nucleotide Polymorphisms (SNPs), Copy Number Variations (CNVs) and repeats of 1000 shortlisted genes in Indian population deemed biomedically significant and pharmacogenetically relevant. This information is consolidated into a database freely accessible to researchers and clinicians. The cardinal genomics and drug response studies in India were led by Indian Council for Medical Research (ICMR) Center for Advanced Research in Pharmacogenomics at Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry till 2012 and continued by CSIR Institute of Genomics and Integrative Biology (IGIB). ICMR has been implementing newer task forces on pharmacogenomics to steer studies on pharmacokinetics, dynamics and genomics in Indian population. Department of Biotechnology (DBT) and Central Drug Research Institute (CDRI) have various initiatives towards this cause. Advancing one step forward at a time, the biotechnology industry in India has translated many of the genomic level studies to drug selection tools. The Imatinib Resistance Mutation Analysis (IRMA) for detecting 90 mutations in ABL domain to predict the efficacy of Imatinib in Chronic Myeloid Leukemia (CML) developed by OncQuest Lab is propitious now. Collaborating with international diagnostic majors, Indian companies like Avasthagen, Action Biotech and TCG Life Sciences have brought genomic, transcriptomic and metabolomic testing panels for virulence in Tuberculosis (TB) and drug efficacy prediction in TB, SLE, Glaucoma, Coronary Artery Diseases and Neuropsychiatric disorders.

Rajiv Gandhi Centre for Biotechnology (RGCB) has been a trailblazer in advocating and materializing personalized medicine through various projects involving diseases posing a burden in Indian health scenario.  Multifactorial chronic diseases are dealt with studies on monocyte protein markers in Type II Diabetes Mellitus, metabolomic profiling to predict the risk of onset of Type II DM, neurodegenerative disorders, gut microbiome in malnutrition and Type II DM. Tailored therapy in Oncology is a promising and fast progressing arena with studies on Nanoparticle mediated targeted drug delivery, chemotherapy efficacy and BRCA1/2 in prostate cancer, induced Pluripotent Stem Cells (iPSCs) for in vitro drug testing, epigenetic landscape in endocrine resistance in breast cancer, prognostic markers for oral squamous cell carcinoma, PAK1 and MTA targeted therapy in breast cancer, cancer informatics and disease prediction modeling tools. With the high incidence of infectious diseases in India, the studies like immune profiles in measles vaccine immunogenicity in selected cohorts in India, virulence studies in Chikungunya and Dengue virus, Tuberculosis, Cholera, Malaria and Leptospirosis are very pertinent. The Laboratory Medicine and Molecular Diagnostics in RGCB provides extensive diagnostic and prognostic platforms for cancer, infectious diseases and cardiovascular genomics with dedicated services accessible to public at affordable costs.

The major hurdle in practicing personalized medicine in India is the lack of awareness of its significance among researchers and clinicians. Pharmacogenomics is complicated, time consuming and exorbitant. The positive results obtained under controlled conditions within the four walls of laboratories can be replicated at a community level only if the markers and platforms are extremely robust. Moreover, prescribing and dispensing customized medicines is a huge burden for clinicians unless patients are very well aware of the consequences.  Let us hope for healthy changes in basic research and clinical practices in India to bring forward better clinical outcome through emerging tools in Biotechnology.

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