Drug Discovery and Clinical Trials Assessment 1
Drug Discovery and Clinical Trials Assessment 1
Assessment 1 - Therapeutic Development Proposal
The lecture content from Weeks 1 to 8 will provide you with knowledge regarding how potential therapeutics are developed and translated into clinical trials in the biotechnology industry. The lectures are integrated with specific case studies to support your learning with real-world examples. In this assessment, you will be tasked to use this knowledge, and survey the existing literature on similar case studies, to develop your own potential new therapeutic. Ideally, this will initially involve the selection of a specific disease which has a key "driver" that is targetable by pharmaceuticals. This may be a disease without current treatments available, or an existing disease where treatments are available, however there is scope for further therapeutic improvement. You will select this disease by Friday of Week 6 (21rd April 2023) and confirm this selection with the Unit Coordinator. Upon approval to proceed, you will develop a written proposal that addresses the following sections:
Part A: Who is your target patient population? What are the key characteristics of the disease that this therapeutic is designed to target?
Part B: What pre-clinical models of the disease would you propose to use to test your therapeutic?
Part C: Describe the pre-clinical toxicity study that you may propose for your therapeutic?
Please note the following as a guide:
The entire written proposal should be from 1,500 to 2,000 words in length.
Accurately describe the disease that you are proposing, including the specific characteristics of the disease that your proposed drug is targeting. This may be a genetic abnormality (e.g. gene translocation or mutation), abnormality in the blood serum biochemistry (e.g. excessive protein or lipid in the blood) etc.
The text should be prepared using a standard word processing software (e.g. Microsoft Word) with the appropriate use of figures, diagrams or tables as required.
Specific referencing to scientific literature is essential. APA or Harvard style is acceptable, and the use of Endnote is highly encouraged.
Therapeutic Development Proposal Plan
Name: Esaba Mashiat
Date: 20/04/2023
Target Disease: Type 1 Diabetes Mellitus (T1DM). [1]
Patient Population: Affects all ages and ethnicities and accounts for 5-10% of all diabetes cases. Highest incidences observed in northern European and Scandinavian countries. Typically diagnosed in childhood or young adulthood. [1, 2]
Disease Etiology: The development can be related to multiple genetic and environmental factors. However, the exact cause is still unclear. [1, 4]
Disease Symptoms: Excessive thirst, frequent urination, unexplained weight loss, nausea, vomiting, and abdominal pain, fatigue, blurred vision, and increased susceptibility to infections. Untreated, it can cause diabetic ketoacidosis which can be fatal. [5]
Limitation of Current Treatments: Current treatments, insulin therapy and lifestyle modifications, aim to manage disease and not cure it. Treatments can cause side effects and require strict patient adherence to be effective. Current treatments also do not prevent long-term diabetes-related complications. [5,6]
Therapeutic Approach: The proposed therapeutic will aim to modify the disease and treat it rather than managing its symptoms. It aims to reprogram genetic factors that cause the immune system to target beta-islet cells.
Proposed Therapeutic: Gene therapy using viral vectors, engineered cells, and small interfering RNAs (siRNAs). Exact therapeutic to be decided after further research. One attractive therapeutic is the use of siRNAs to inhibit the expression of genes involved in the autoimmune attack on beta cells. [7, 8, 9]
Biological Targets: Specific genes involved in immune responses and/or pancreatic beta cell differentiation. Possible targets include: Pdx-1, Neurogenin3, Foxp3, and IL-10. [7, 8, 9]Pdx-1 and Neurogenin3 are involved in the development and differentiation of pancreatic beta cells. Foxp3 and IL-10 modulate the immune response to prevent destruction of beta cells.
References
Atkinson, M. A., Eisenbarth, G. S., & Michels, A. W. (2014). Type 1 diabetes. The Lancet, 383(9911), 69-82. https://doi.org/10.1016/S0140-6736(13)60591-7International Diabetes Federation. (2019). IDF Diabetes Atlas. 9th Edition. https://www.diabetesatlas.org/en/Coppieters, K. T., & von Herrath, M. G. (2015). Histopathology of type 1 diabetes: old paradigms and new insights. Reviews in Endocrine and Metabolic Disorders, 16(1), 25-35. https://doi.org/10.1007/s11154-015-9302-8Pociot, F., & Lernmark, . (2016). Genetic risk factors for type 1 diabetes. The Lancet, 387(10035), 2331-2339. https://doi.org/10.1016/S0140-6736(16)30582-7American Diabetes Association. (2021). Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2021. Diabetes Care, 44(Supplement 1), S15S33. https://doi.org/10.2337/dc21-S002National Institute of Diabetes and Digestive and Kidney Diseases. (2016). Type 1 Diabetes. https://www.niddk.nih.gov/health-information/diabetes/overview/type-1-diabetesFerreira, A. V. M., Zaverucha-do-Valle, C., Carvalho, J. L., Abdelhay, E., & Bouas, A. P. (2017). Gene therapy: a new approach to treat type 1 diabetes mellitus. Current Gene Therapy, 17(5), 342-355. https://doi.org/10.2174/1566523217666170602151244
Pasquale, V., Martire, S., Giacco, F., & Castaldo, G. (2021). Gene therapy in type 1 diabetes mellitus: A systematic review. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 15(2), 487-493. https://doi.org/10.1016/j.dsx.2021.01.026
Vasu, S., Moffett, R. C., McClenaghan, N. H., Flatt, P. R., & Gault, V. A. (2020). Novel therapeutic approaches for the treatment of type 1 diabetes mellitus. Biochemical Pharmacology, 181, 114106. https://doi.org/10.1016/j.bcp.2020.114106
