Team:IISER Bhopal/Description
Description
"Synthetic biology can help address key challenges facing the planet and its population. Research in synthetic biology may lead to new things such as programmed cells that self-assemble at the sites of disease to repair damage."
- Craig Venter
Global Crisis
Diabetes mellitus is a chronic metabolic disorder caused due to insufficient insulin production in the pancreas or abnormal insulin regulation in the body. Insulin, a peptide hormone, is essential to regulate blood glucose levels in the body. Hyperglycemia due to insufficient insulin production can lead to multiple organ failure and ultimately death.
There are currently 150-200 million insulin-dependent diabetics across the globe. Due to the expensive nature of treatment, a significant population remains untreated. Insulin dependence is on the rise, and it is estimated that the global economic burden due to diabetes will be $2.5 trillion by 2030. With rapidly increasing numbers, an affordable and patient-friendly alternative is a dire need.
Type 1 diabetes
The onset of type 1 diabetes usually occurs during childhood. It is believed to be an autoimmune condition where the immune system attacks by mistake and destroys the β cells in insulin producing pancreas. There may be both genetic and environmental reasons. Lifestyle factors do not play arole.
Type 2 diabetes
Type 2 diabetes starts as insulin resistance. This means one’s body can’t respond to insulin signals efficiently. This stimulates one’s pancreas to produce more insulin until it can no longer keep up with demand. Islet cells begin to die from stress, causing insulin production to decrease, which in turn leads to high blood sugar.
The exact cause of type 2 diabetes is unknown. Contributing factors may include:
Epidemic in India
India is home to one in six diabetic patients across the globe. As number two in the world, India is also considered as the diabetes capital. The estimated number of diabetics in India is a whopping 77 million. The prevalence is higher in urban areas and is in the range of 10.9% and 14.2%. Prevalence in rural areas is lower (3.0-7.8%). This lifestyle disease is afflicting populations aged 20 years and above with a much higher prevalence among individuals aged over 50 years. Although Type II diabetes is managed with oral hypoglycemics about 30% of this group is also insulin-dependent. Escalating numbers is a matter of serious concern, dictating the need for affordable and patient-friendly alternate therapies.
134,000,000
Diabetes cases projected in India by 2045.
4 in 10
Diabetics use insulin injections In India.
76%
Indian diabetics have uncontrolled diabetes.
Current Treatments
Existing diabetes treatments aim to tackle diabetes through therapies involving injections, Oral hypoglycemics, etc. In India, insulin injections are the most widespread form of diabetes treatment for insulin-dependent patients and are administered at a frequency of 2 to 4 times a day. Most existing treatment options, owing to the chronic nature of the disorder, are expensive and inconvenient.
As per our interactions with experts, the biggest issue in India with any form of conventional insulin therapies is the variation in insulin absorption rates across recipients even with the injection. The pain associated with daily injections also creates psychological trauma and often decreased compliance, leading to diabetic complications.
An oral insulin formulation would provide a boon for insulin-dependent patients, be user-friendly and ensure compliance. Nevertheless, being a peptide hormone, insulin administered orally would degrade in the GI-tract. The lacunae in the treatment for such a widespread lifestyle disorder has been a key driving force in our decision to work on diabetes.
The cost of one insulin injection in India is between ₹140 - ₹450, whereas the median salary of an Indian is around ₹350. It is near impossible for a person to afford the treatment on a regular basis.
As per data, there is rampant reuse of insulin injections for single use only, among Indian patients which is dangerous to their health.
There is increased chances of lipohypertrophy with regular use of needles, due to fat granules depositing under the skin leading to lowered insulin absorption in the blood.
Incorrect usage of insulin injections could lead to tissue damage and infections.
Our Solution
Unlike other forms of insulin treatment that focus on administering insulin externally to patients through injections, we are focusing on the root cause. Insulin deficiency in diabetes patients is due to damaged beta cells in the pancreas. Our project aims to substitute damaged β cells in the pancreas with functional islet-like cells in the gut capable of insulin production in-vivo. We propose creating a capsule containing enhanced probiotic bacteria capable of transforming intestinal crypt cells into insulin-producing, glucose-responsive β-islet like cells.
Our therapy is based on the principle of transdifferentiation which involves reprogramming one cell type into another. We intend to clone an FDA approved probiotic - E. coli Nissle 1917, with the three transcription factors essential for insulin production. These three factors will be injected into the newly differentiated intestinal crypt cells, with the aid of a ‘molecular syringe’ called EPEC T3SS found in Gram-negative bacteria. The attachment of our chassis and injection of effector proteins into the crypt base columnar cells will reprogram them, allowing insulin production in the gut. The BIG PIE would therefore provide an out-of-the-box and viable approach to tackle diabetes.
