Advancing Translational Sciences

The process of turning observations in the laboratory, clinic and community into interventions that improve the health of individuals and the public — from diagnostics and therapeutics to medical procedures and behavioral changes.

National Institute for Advancing Translational Sciences (NCATS).

Basic Lab Research – Scientific exploration of basic principles and fundamental mechanisms of disease biology.

-Pathways -Mechanisms -Genes e.g.CEP290 -Targets e.g.pre-mRNA -Biomarkers

Pathogenesis of retinal ciliopathies.1 Role of CEP290 protein in transport of other proteins via the cilium’s transition zone.

Pre-clinical Research – Science of disease and human medicine.	-cell cultures -tissues -animal models -computer modeling	Patient -> skin biopsy -> fibroblasts -> induced pluripotent stem cells (iPSCs) -> differentiated into 3D self-organizing tissue of human retinal organoids. Used as an in vitro models to evaluate AONs-based drug candidates.
Pre-clinical Research – Science of disease and human medicine.	-cell cultures -tissues -animal models -computer modeling	Use of antisense oligonucleotide (AON) to prevent binding of the splicing factors to mRNA, as a result to make photoreceptors synthesize full length CEP290 protein.
Pre-clinical Research – Science of disease and human medicine.	-cell cultures -tissues -animal models -computer modeling	Appropriate genetic mutants such as mice or Zebrafish or Xenopus.

Clinical Research – Testing of new medicine in the human body.	-Phase I -Phase I/II(rare disease) -Phase II -Phase II/III (r.d.) -Phase III -Phase IV …	Phase I Clinical Trial – Study of effects of the new medicine on healthy volunteers with no underlying health conditions. Safety study. To find the highest dose without serious adverse effects.
Clinical Research – Testing of new medicine in the human body.	-Phase I -Phase I/II(rare disease) -Phase II -Phase II/III (r.d.) -Phase III -Phase IV …	Phase II Clinical Trial – Study of effects of the new medicine on patients who are living with the disease condition (LCA10). To learn how effectively the new medicine treats the disease. To continue monitoring safety and side effects.

Phase III Clinical Trial – Study of long-term effects of the new medicine that has been adopted from the research in patients into a routine clinical care in the larger general population.(Heterogeneous population that is varying in severity of disease progression, age etc.) Implementation of the new and useful medicine. To demonstrate that the new medication is at least as safe and effective as the available treatment options. (In case of rare diseases 95% still do not have any treatments.)

Phase IV Clinical Trial– Study of impact of the medication’s long-term safety, effectiveness, and any other benefits in the general population in practice. Post-marketing studies after the medication has been FDA/EMA approved.

T5 Translation Level –
Impact on the well-being of the global population by implementing structural societal changes, universal health care access, political security, and education.

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References:

1. Holly Yu Chen, Emily Welby, Tiansen Li and Anand Swaroop; Retinal disease in ciliopathies: Recent advances with a focus on stem cell-based therapies; Translational Science of Rare Diseases 4 (2019) 97–115;
2. Scott A. Waldman, Andre Terzic; Clinical and Translational Science: From Bench-Bedside to Global Village; Clinical and Translational Science; (2010), 3(5);