Disease models aid in understanding the cause of a disease by being used to mirror a disease and its processes. Disease models can include cells grown in a petri dish or organisms that lack specific cells, tissues, or organs. These can be studied under controlled conditions within the laboratory, which removes the external factors affecting humans in a normal environment. Other types of disease modeling comprise computer and statistical models.
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The use of disease models can be used to study many common diseases and disorders, including the role of individual genes in cancer development, the response to drugs within different diseases, and biological processes. Investigating diseases through this comprehensive method can allow researchers to discover new approaches for potentially novel drug development and treatments.
Drug development is lengthy, complex, and expensive, with 90% failing to achieve Food and Drug Administration (FDA) approval. This is due to many challenges that are involved in the intricate drug development process, which include: the discovery stage of finding a biological target and synthesizing the drug, the preclinical trials that assess the safety and biological activity in animals, as well as the clinical trials stage that assesses the safety and dosage of drugs in humans.
After the clinical trials stage, the drug is reviewed for FDA approval to ensure the safety and efficacy of the drug, which then enables the drug to be available on the market for patient use, while post-approval trials take place on broader patient populations for investigating long-term efficacy.
This time-consuming process can also be extended if a drug fails FDA approval due to not having strong enough evidence for its lack of safety or efficacy against a disease – this can cause a pharmaceutical company to continue clinical trials for a longer period or re-evaluate its strategies overall.
The comprehension of disease pathophysiology can be a significant challenge within drug development as unknown pathophysiological processes can make target identification difficult, influencing the probability of success of drug candidates.
This can occur for nervous system disorders, including neurodegenerative diseases such as Alzheimer’s disease or Parkinson’s, which are challenging treatment areas due to the lack of cures available. Improving the efficacy of disease models in this area could improve the understanding of biological targets, which may also improve drug development and treatment.
Other challenges include heterogeneity of the patient population, as this can result in diseases that express differently in various patients, which may affect treatment efficacy. Advanced sequencing methods can aid in understanding the signaling pathways and biological targets involved in the pathophysiology of human disease, while disease models can be used to test novel targeting approaches geared towards new markers within diseases.
Approximately 80% of rare diseases have a genetic cause, with 40% comprising neurologic and neurodevelopmental disorders; while the exact cause of these diseases is unknown, disease models that explore the genetic component of neurological diseases have a higher likelihood of finding a promising strategy.
Rare disease research can include in vitro approaches that use cell or tissue culture to predict clinical disease outcomes. Testing strategies within the laboratory can ensure various treatment approaches are being assessed, with the optimum strategy being advanced into the next stage.
While this approach to disease modeling is helpful for various diseases, it can be challenging to use cell culture to mimic the pathophysiology of rare diseases. CRISPR, a novel genome editing technology, can aid in alleviating this problem as this editing innovation can expand the range of cell and animal modeling systems used as disease models.
An example of this includes the zebrafish species that share 71% of the same genes as humans and can be used to study rare genetic variants. Additionally, mice are also used for disease modeling, with this species sharing 85% of its genes with humans and possessing the same major organ systems. This allows the testing of drug candidates within species that may have similar symptoms and responses to the treatment, which aids in gauging the overall efficacy without harming humans.
Exploring genetic variants that cause disease in animals can assist in comprehending how the disease is caused and their pathophysiology, which can become biological targets for future drug development.
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The efficacy of disease models holds an important role in biomedical research and the field of medicine, with researchers using these as a strong foundation for drug discovery and development.
This can aid in accelerating the drug development process, as having an effective disease model that demonstrates the efficacy of a possible drug can ensure responses are being measured and optimum drug candidates are being advanced to the next stage at a faster rate. Additionally, streamlining this strategy through the use of high-sequencing genomic tools as well as novel technology, such as CRISPR may be revolutionary for the future of drug development, with accelerated treatments being developed and approved for both widespread and rare diseases.
- Forum on Neuroscience and Nervous System Disorders; Board on Health Sciences Policy; Institute of Medicine. Improving and Accelerating Therapeutic Development for Nervous System Disorders: Workshop Summary. Washington (DC): National Academies Press (US); 2014 Feb 6. 2, Drug Development Challenges. Available from: https://www.ncbi.nlm.nih.gov/books/NBK195047/
- Madabushi, R., Seo, P., Zhao, L. et al. Review: Role of Model-Informed Drug Development Approaches in the Lifecycle of Drug Development and Regulatory Decision-Making. Pharm Res 39, 1669–1680 (2022). https://doi.org/10.1007/s11095-022-03288-w
- Son, M., Kim, D.Y. and Kim, C.-H. (2022) “Disease modeling of rare neurological disorders in zebrafish,” International Journal of Molecular Sciences, 23(7), p. 3946. Available at: https://doi.org/10.3390/ijms23073946.
- Zhu, H. (2021) U.S. Food and Drug Administration, Role of Disease Models in New Drug Development and Approval. FDA. Available at: https://www.fda.gov/media/155414/download (Accessed: November 17, 2022).