The efforts to develop new molecules to treat diabetes, schizophrenia, asthma, pancreatitis, and coronary artery disease, have made good progress during the last five years under different institutes of Council of Science and Industrial Research (CSIR), according to an assessment report.

“Indian Institute of Chemical Biology (IICB) synthesized nearly 400 new molecules based on the selected anti-diabetic drug targets i.e. DPP-IV, PTP1b and GLP-1, alpha-glucosidase, glucose-6-phosphatase, glycogen phosphorylase, and aldose reductase and evaluated against their putative targets. Three new molecules showed inhibition against PTP1b, whereas nine new molecules showed inhibition against DPP-IV. One of glucose-6-phosphatase and two alpha-glucosidase inhibitors showed anti-hyperglycaemic activity on streptozotocin-induced diabetic rats,” according to the report.

In addition, at CSIR-run Central Drug Research Institute (CDRI), eight promising anti-diabetic molecules were further explored for their in vivo efficacy. Transcriptomic analysis has revealed a novel mechanism of action of compound S-001-469 for which US patent has been granted. Pharmacokinetic and stability studies have been completed in two new NCEs.

“INDICO (Indian Diabetes Consortium), a network of clinicians and researchers from major research laboratories from all over India has been established. An in silico disease gene prediction method for type 2 diabetes has been developed. At CSIR-IGIB Genome-wide association study (GWAS) involving 2500 participants from North India belonging to Indo-European ethnicity has indicated that new genes and pathways are involved in the patho-physiology of type 2 diabetes in Indians. Genetic methylation studies have suggested that at least twelve genes have six fold differences in methylation levels and these differentially methylated genes belong to important pathways related to type 2 diabetes,” the report said.

“Institute of Genomics & Integrative Biology (IGIB) examined 108 (730 SNPs) novel positional candidate genes for association in schizophrenia and bipolar disorder samples from southern India. This has finally led to the identification of one gene that shows association with bipolar disorder. Additionally, in a replication study, evidence for interaction between two dopaminergic pathway genes was obtained in schizophrenia,’’ it said.

CSIR-IGIB scientists demonstrated that Ovalbumin induced experimental allergic asthma in BALB/c mice is associated with mitochondrial dysfunction. It also reported the association of mitochondrial structural changes and dysfunction with experimental allergic asthma. These findings may help in the development of novel drug molecules targeting mitochondria for the treatment of asthma, as per the report.

“The Centre for Cellular and Molecular Biology (CCMB) sequenced the complete lysosomal hydrolase Cathepsin B (CTSB) gene in an adequately powered cohort with a large number of well-characterized patients and healthy controls and identified several variants spread across the gene. This work provides the first human-based evidence for the 30-year-old cathepsin B hypothesis of pancreatitis and suggests CTSB gene as the second candidate gene, after SPINK1 gene, to be involved in the pathogenesis of TCP. Understanding the functional basis of mutations in these genes may help in development of predictive tests for susceptibility to chronic pancreatitis,” it said.

Likewise, several recent genome-wide association studies (GWAS) have reported the association of multiple single nucleotide polymorphisms (SNPs) mainly in the 9p21 region with Coronary artery disease (CAD). However, the association of these SNPs with CAD has not been rigorously tested in Indian population, which accounts for the largest incidences of CAD in the world.