CRISPR therapy that increases the expression of MPN factors so the pancreas can produce insulin again. Stage one involves experimenting with organoids. Stage two woudl be animal trials and in the end, the purpose is to create an injection that cures existing beta cells once and for all instead of
Affecting more than 400 million people worldwide according to the World Health Organization, diabetes is a chronic disease that has been treated mainly by the administration of insulin into the patient's bloodstream or by prescribing medicines like metformin to control the levels of glucose.
In 2017, men spent $10,060 and women spent $9,110 on medical expenditures related to diabetes. A patient with this condition can spend more than $3,000 each year on their treatment. Considering that this is chronic disease, the costs multiply every year. Thus, the necessity of not only a treatment, but a cure for diabetes seems evident.
The recently discovered genetic engineering tool, CRISPR (Clustered Regularly Interspaced Palindromic Repeats) unveals an opportunity to take a differen approach for genetic-related diseases. With the ability to target any site in the genome, CRISPR culd be used to reactivate genes that were turned off i-n diabetes, ultimately making an epigenetic change.
In the process of durg approvals, the usual method is animal trials. The animal that shows more genetic resemblance with humans is the mouse. Nevertheless, it has also been shown that this cannot be accurate enough, appart from ethical concerns involved. Therefore, in this research human organoids will be used as a more accurate method of and observation and prediction.
Finally, adjusting the materials to the budget, the device used for transfection will be one called ElectroPen. Designed to do genetic engineering experiments, this creative apparatus offers the possibility of creating competent cells at a more affordable cost.
FGF21
In humans, FGF21 is a starvation-induced protein that is elevated after 7 days of fasting and regulates the utilization of fuel to adapt metabolism in the late phase of the absence of nutrients (Fazeli et al., 2015).
This gene is expressed in several tissues such as liver (Nishimura et al., 2000), adipocytes (Zhang et al., 2008), pancreas (Johnson et al., 2009), and brain where it passes the blood-brain barrier (Hsuchou et al., 2007). The liver is considered to be the main site of FGF21 production positively controlling the PI3K/AKT, insulin-like growth factor 1 (IGF-1) and mTOR pathways as well as triglyceride homeostasis, glucose uptake, amino acid transport, and energy expenditure (Muise et al., 2013).
Worth mentioning, there is a positive correlation with elevated serum FGF21 levels and metabolic disorders like obesity, diabetes, mitochondrial diseases, and aging. (Staiger et al., 2017; Tezze et al., 2017). Circulating FGF21 levels are elevated in various metabolic disease states, such as obesity, insulin resistance, and type 2 diabetes mellitus (Zhang et al., 2008; Chavez et al., 2009)
PDX1
Also known as Insulin Promoter Factor 1, PDX1 is a homeodomain transcription factor required for early embryonic development of the pancreas as well as for the subsequent differentiation of pancreatic lineages. Similar to HNF4A, this protein is also responsible for the functioning of the GLUT2 and glucokinase that are solely responsible for the uptake of glucose into the cells.
PDX1 protein shows increased interaction with transcription activators such as PBX1. It forms complex with PBX1 and MEIS2b (Homeobox protein Meis2) proteins in the pancreas. This complex further activates the ELA1 transcription. This complex binds to the B element of the protein and increases the transcriptional activity of PTF1 (Pancreas transcription factor 1).
In mature beta cells, depletion and reduction of PDX1 induces glucose intolerance, which suggests the critical role of PDX1 in maintaining beta cell function. In human type 2 diabetes mellitus (T2D), PDX1 expression levels of islet beta cells are compromised. In addition, a polymorphism in the coding region is associated with increased risk for type 2 diabetes.