What is Forward Translation?
Generally, forward translation is the process that translates a word, phrase, text, or task into another or the target language. In the process of drug discovery, forward translation, also known as "from bench to bedside", is used to describe the process from basic research in the laboratory to the development of new drugs and new therapies.
Usually, the process of drug discovery research mainly consists of two stages: basic and applied research (preclinical and clinical research), of which basic research is to explore the molecular mechanisms of diseases or drugs, while, applied research is to advance and apply these basic discoveries for clinical and patients. The forward translation is a tried-and-true approach wherein the basic discoveries in molecular biology are harnessed for the development of new drugs and therapies. When specifically applied for neuroscience, the forward translation (or translational neuroscience) is commonly used for integration of basic neuroscience research with clinical trials for the development of novel therapies for nervous system disorders. It is essential for the development of preclinical models of neurological diseases, such as psychiatric disorders, so as to gain an in-depth insight into their etiology and progression, and to identify new targets or markers for effective treatments.
Target Identification and Verification Through Forward Translation
Translational neuroscience research usually begins with the identification of disease-associated genetic variation, aiming to reveal the molecular mechanisms of neurological diseases and to achieve desirable therapeutic effects in a patient population. Modern genetically engineering animal modeling improvement and advanced biological technologies, such as electrophysiology, neuroimaging, and induced pluripotent stem cells, provide multiple opportunities for biological target identification and validation, as well as new treatment development of psychiatric disorders by the approach of forward translation.
Cases for psychiatric target identifications and novel drug discoveries are numerous. Take one example, metabotropic glutamate receptor 5 (mGlu5) was identified as a target for the treatment of Fragile X syndrome, a genetic psychiatric disorder characterized by mild-to-moderate intellectual disability. mGlu5 is a metabotropic receptor for the excitatory neurotransmitter L-glutamate, both of which are involved in normal brain function and neuropathologic conditions. mGlu5 inhibitors have been developed and validated in animal models. And it has been found that inhibition of the activity of mGlu5 could, to varying degrees, correct multiple disease-related phenotypes in fragile X mental retardation 1 (FMR1) gene knockout mice. When translating into clinical trials in humans, however, two of these mGlu5 inhibitors (basimglurant and mavoglurant) did not work as preclinical expected in Fragile X syndrome patients (Scharf, 2015).
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