Next generation treatments for type I diabetes – Biology vs Engineering

Some time ago I produced an article for the science website Apptheneum on the future of type I diabetes treatments which focused on gene and cell therapy as potential cures:

http://www.apptheneum.com/next-generation-treatments-type-diabetes/

These are purely biological solutions, however the engineers also have their own.

The solution offered by the engineers has one distinct advantage – the immune system is irrelevant. One of the problems of using gene or cell therapy is that type I diabetes is an autoimmune disease. This means that even if you “cure” the disease it is likely to recur unless the underlying immune dysfunction is also dealt with or circumvented. There is a long way to go on this front. The engineers solution is an artificial pancreas which is not exposed to the immune system as it rests outside of the body.

“The artificial pancreas is not a replica organ; it is an automated insulin delivery system designed to mimic a healthy person’s glucose-regulating function”:

http://news.harvard.edu/gazette/story/2016/01/artificial-pancreas-system-aimed-at-type-1-diabetes-mellitus/

You can argue as to whether the name is appropriate as blood glucose regulation is only one aspect of the function of the pancreas but I’m sure someone has already. The NIH launched a $20 million program to fund artificial pancreas clinical trials in 2014:

http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-16-008.html

So it looks like improved insulin delivery devices will become available in the not so distant future. However the problem with non-biologically engineered solutions is that they cannot perfectly regulate blood glucose levels (as cell and gene therapies potentially can) and it is likely that over time people with type I diabetes using artificial pancreases will still develop problems with their feet associated with reduced circulation and nerve damage. Cardiovascular disease, retinopathy (eye damage), general nerve damage, kidney disease, and sexual dysfunction will still be major problems. However artificial pancreases will no doubt be a vast improvement over manual insulin injection.

For this reason I believe that the engineers will win the race but lose the war. It is only a matter of time until the immune system is understood to a level where the underlying autoimmune disease can be dealt with.

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The pancreatic cancer database – an excellent resource

The pancreatic cancer database1 is a one-stop shop for finding information derived from the literature on the expression levels of mRNA, miRNA, and protein in pancreatic cancer:

http://pancreaticcancerdatabase.org/index.php

It has been produced by the team behind the 2009 PLOS Medicine paper2 which catalogued a list of potential biomarkers for pancreatic cancer using an algorithm that examined microarray databases and the published literature for overexpressed mRNAs and proteins.

You can search by gene or protein identifiers or browse by gene symbol. All results are hyperlinked to the relevant PubMed entries.

It should be noted that the database is not complete. For example searches for “CDCP1” (there is data in the literature) or “IL24” yield no results.

The database is a useful resource to quickly check the status of a gene of interest. However the results are not fine grained. Microarray data is reported as average fold change. Pancreatic cancer is an extremely heterogeneous disease and it is worth keeping in mind that average fold change can mask important outliers. It is the outliers that are interesting/ important.

It is certainly worth taking a closer look at the underlying microarray data. This will require some processing and analysis. However the R statistical programming language and various web resources such as CARMAweb3 make this relatively straightforward:

https://carmaweb.genome.tugraz.at/carma/

  1. Thomas, Joji Kurian, Min-Sik Kim, Lavanya Balakrishnan, Vishalakshi Nanjappa, Rajesh Raju, Arivusudar Marimuthu, Aneesha Radhakrishnan, et al. ‘Pancreatic Cancer Database: An Integrative Resource for Pancreatic Cancer’. Cancer Biology & Therapy 15, no. 8 (August 2014): 963–67. doi:10.4161/cbt.29188.
  2.  Harsha, H. C., Kumaran Kandasamy, Prathibha Ranganathan, Sandhya Rani, Subhashri Ramabadran, Sashikanth Gollapudi, Lavanya Balakrishnan, et al. ‘A Compendium of Potential Biomarkers of Pancreatic Cancer’. PLoS Medicine 6, no. 4 (7 April 2009): e1000046. doi:10.1371/journal.pmed.1000046.
  3.  Rainer, J., F. Sanchez-Cabo, G. Stocker, A. Sturn, and Z. Trajanoski. ‘CARMAweb: Comprehensive R- and Bioconductor-Based Web Service for Microarray Data Analysis’. Nucleic Acids Research 34, no. Web Server (1 July 2006): W498–503. doi:10.1093/nar/gkl038.