Editing Openai/692df380-fd64-8008-b788-94e93ef3ff89 (section)

==== 5. Safety, trade-offs, and potential risks ====

Preclinical data highlight that KMO inhibition is not an unambiguous win:
# Excess KYNA and cognition/mood - Mice with KMO deficiency (high KYNA) display depression-like behavior, attributed to enhanced antagonism of α7-nicotinic receptors by KYNA. ScienceDirect<ref>{{cite web|title=ScienceDirect|url=https://www.sciencedirect.com/science/article/abs/pii/S0166432821000796|publisher=sciencedirect.com|access-date=2025-12-28}}</ref> - Elevated KYNA and KMO knockout models impair spatial working memory and LTP; KAT II inhibition (reducing KYNA) restores glutamatergic signaling and LTP. PMC<ref>{{cite web|title=PMC|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8411644/|publisher=pmc.ncbi.nlm.nih.gov|access-date=2025-12-28}}</ref> - Human data associate high brain KYNA with cognitive impairment in schizophrenia and possibly other conditions. Wiley Online Library<ref>{{cite web|title=Wiley Online Library|url=https://onlinelibrary.wiley.com/doi/10.1111/cns.13768|publisher=Wiley Online Library|access-date=2025-12-28}}</ref> Implication: Over-inhibiting KMO (and thus over-producing KYNA) may trade neuroprotection for impaired cognition and mood.
# NAD⁺ metabolism - QUIN is a precursor for de novo NAD⁺ synthesis. Chronic, strong KMO inhibition might slightly alter NAD⁺ homeostasis, especially in tissues reliant on de novo synthesis. Reviews acknowledge this but the net impact in vivo is unresolved. PMC<ref>{{cite web|title=PMC|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8747024/|publisher=pmc.ncbi.nlm.nih.gov|access-date=2025-12-28}}</ref>
# Unknowns in long-term systemic inhibition - No long-term human data on infection risk, tumor surveillance, metabolic side-effects, or subtle CNS changes. - KMO is expressed in immune cells; chronic inhibition could theoretically modulate host defense, but data are sparse. PMC<ref>{{cite web|title=PMC|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8747024/|publisher=pmc.ncbi.nlm.nih.gov|access-date=2025-12-28}}</ref>