Mordechai Nosrati

individual

1

These concepts and the proposal are the results of my 26 years of extensive academic and clinical experience teaching, treating and prescribing all forms of renal disease most specifically the diabetic nephropathy a disease that develops as a result of uncontrolled diabetes in both Type 1 and Type 2 Diabetes (T1DM and T2DM).

For example, Type 1 Diabetes (T1DM) accounts for approximately 5% of all diabetes and affects about 20 million individuals worldwide. The U.S. prevalence estimate ~3 million T1DM patients and it is estimated to triple by 2050 due to a rising incidence of T1DM Worldwide. In addition, Incidence has been rising by approximately 3% per year with annual direct medical expenses and indirect costs such as lost income amount to $14.4 billion.

It should be noted that diabetes is a multisystem disease and a life-changing event affecting both mental and physical health -this is even more evident in younger patients who suffer from T1DM. T1DM affects patients systemically, and its complications include cardiovascular disease (CVD, CHF, Heart Attack), renal/kidneys (CKD, ESRD), nervous system (Joint Destruction, amputation), retinopathy (Blindness) and Vascular ((PVD, Ischemia, Amputation) which are the major causes of morbidity and mortality not to mention the well-known morbidity and mortality of hypoglycemia and diabetic ketoacidosis (DKA). Hence, it is evident that complications of diabetes can be devastating not to mention the tremendous burden on the healthcare budget.
Furthermore, the treatment is too complex to be able to make it fully automate. Majority of patients are failing to reach their A1c goals which is not due to lack of patient’s compliancy! Even with tremendous amount of effort and time we cannot emulate the endocrine pancreas physiologically! The current treatments such as blood glucose meter, continuous glucose monitor, insulin pen, Insulin pump, ,Jet injectors and even Pancreas Transplantation and Islet Cell Transplantation have their own issues and complications. Hence the need for a “True Cure” via fabricating bioengineered organ.
Currently, our best option is through 1)Pancreas Transplantation (problematic) 2) Islet Transplantation (problematic) or 3)Bio-artificial Pancreas (best approach for the near future). However, currently available treatments fail to even come close to replacing a normal pancreas! Even the automated insulin pumps don’t come close as they don’t emulate a true pancreas. The closest treatments are the Pancreas and Islet transplantation. Nevertheless, both Pancreas Transplantation and Islet [insulin producing cells] Transplantation are:
1.Too expensive
2.Too invasive,
3.Require lifelong immune system suppression
4.In case of Islet Tx, you sacrifice 3-4 good pancreas
5.Shortage of Organs (need to use the pancreas grafts more efficiently)

For example, the problems with Islet Transplantation are as follows: it is very Expensive (~ $20,000+) , too wasteful since to get enough Islets for one Islet Transplant, they have to be isolated from several donors pancreata. In addition, 20-30 percent of Islets -called Mantle Islets are routinely discarded because a bit of pancreatic tissue is attached and doesn’t allow proper and enough oxygenation of these highly metabolic active Islets. Hence these Mantle islets die and cause necrosis and inflammation. This is unfortunate, since there is a huge shortage of organs. The islets are then infused through a major vein that feeds into the liver. Once established, the islets begin producing insulin in response to changing blood sugar levels. However, these sets don’t last too long due to patient’s immune system which attack foreign tissue! Hence the great need for chronic and long-term immunosuppression.
Therefore, the great unmet need for bio-artificial pancreas that emulates true endocrine pancreas. Hence, the need for a small, biomimetically designed pancreas. To form a biomimetically-designed artificial organ, one must provide a similar architecture with proper capillaries. The mPANCREAS is based on a core technology that provides modular, adjustable and scalable microfluidic chipsets modules that can be utilized to create numerous basic units that emulate all different varieties of capillaries and lymphatics in the human body. This biomimetically designed, microfluidic-based Capillaries and Lymphatic Technology (MCAL Technology) is constructed by manufacturing microfluidic-based multitude of micro-channels to emulate tiny capillaries and lymphatics. These microchannels are designed and manufactured in various shapes (straight, parallel, crisscross, fractal, loop, and branched), forms and configuration with various aspect ratios using diverse types of inert and biocompatible microfluidic polymer substrates. Then using diverse types of semipermeable membranes which have different chemical and physical characteristics and molecular weight cut off (MWCO) values to construct two or more layer constructs in which various semipermeable membranes are sandwiched in between a couple or multiple layers of these microfluidic layers containing varieties of microchannels with different aspect ratios and configurations. As a result this design and construct, the core technology will produce smaller dimension channels that can approach human capillaries and lymphatic to achieve biomimetic properties. By changing the microfluidic layers and /or the semipermeable membranes this core technology will provide an array of different types of microfluidic-based chipset modules which are the basic building blocks for constructing different medical devices with much higher efficiency such as many different forms of dialysis, water purification, bioreactors, and most importantly bio-artificial organ support systems.
The followings will be achieved via mPANCREAS Bio-Artificial pancreas to satisfy the unmet needs in T1DM:
1. Improving the quality of life for T1D patients.
2. Improving their productivity.
3. Improving the glycemic control safely, effortlessly, on demand and physiologically.
4. Reducing complications of T1D
5. Reducing morbidity and mortality
6. Reducing daily and overall Cost of treatment

Thank you
Mordechai Nosrati

NA

pending