Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System Workshop Summary (2011) / Chapter Skim
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5 Challenges and Opportunities
5 Challenges and Opportunities
Pages 33-38
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From page 33... ...
The few biomarkers tied to glutamate function have not advanced far enough to allow for simple "go/no go" measures of drug effect on glutamate in the brain. Workshop participants highlighted four key features of the glutamatergic system that are hurdles for biomarker research: • T he diversity of glutamate's functions and the ubiquity of its ex pression in CNS pathways can lead to widespread pathology and greater likelihood for adverse effects with non-specific treatment; • T he plasticity of the glutamate synapse is an important feature of glutamate transmissions, but can be highly damaging and difficult to control in disease states; • G lutamate physiology versus pathology depends on relatively mi nor differences in glutamate concentrations; and • T ight control over normal glutamate neurotransmission is exerted by at least 30 proteins found at the synapse.
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From page 34... ...
The key is to advance understanding in the glutamate system and provide opportunities for drug development that have not yet been realized. OPPORTUNITIES Biomarkers hold the key; they are vital to refine targets, provide proof of mechanism, provide proof of concept, and evaluate whether early intervention focused on a single target can prevent or forestall disease.
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From page 35... ...
Another reason to broaden PET ligands is to develop molecular targets that stratify with different types of a particular disease. Most psychiatric disorders, for example, are viewed as a heterogeneous mix of disease subtypes.
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From page 36... ...
Several workshop participants said they believed biomarkers should be linked to disease endophenotypes and be less contingent on symptom reporting. Their expectation is that specific endophenotypes might transcend descriptive disease categories and could be found in both schizophrenia and schizoaffective disorder, or in both depression and anxiety.
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From page 37... ...
All of these factors slow progress -- progress that could be accelerated with combined efforts. SUMMARY Despite the challenges, participants expressed enthusiasm that glutamate-related drugs will be developed in the near future, especially with coordinated investment in biomarker development.
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