Drug Treatments for Neurodevelopmental Disorders: Targeting Signaling Pathways and Homeostasis

Purpose of the Review Preclinical and clinical evidence support the notion that neurodevelopmental disorders (NDDs) are synaptic disorders, characterized by excitatory-inhibitory imbalance. Despite this, NDD drug development programs targeting glutamate or gamma-aminobutyric acid (GABA) receptors ha...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Current neurology and neuroscience reports Ročník 25; číslo 1; s. 7
Hlavní autoři: Kaufmann, Walter E., Luu, Skylar, Budimirovic, Dejan B.
Médium: Journal Article
Jazyk:angličtina
Vydáno: New York Springer US 01.12.2025
Springer Nature B.V
Témata:
Animals
Cell signaling
Clinical trials
Drug development
Fragile X syndrome
Genetic diversity
Homeostasis
Homeostasis - drug effects
Humans
Intellectual disabilities
Medicine
Medicine & Public Health
Neurodevelopmental disorders
Neurodevelopmental Disorders - drug therapy
Neurodevelopmental Disorders - genetics
Neurology
Neurosciences
Neurotransmission
Neurotransmitter receptors
Pathophysiology
Rett syndrome
Review
Signal transduction
Signal Transduction - drug effects
Topical Collection on Pediatric Neurology
γ-Aminobutyric acid
Homeostasis
Drug trial research
Mitochondrial dysfunction
Neurodevelopmental disorders
Excitatory/inhibitory balance
Cell signaling
ISSN:1528-4042, 1534-6293, 1534-6293
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:Purpose of the Review Preclinical and clinical evidence support the notion that neurodevelopmental disorders (NDDs) are synaptic disorders, characterized by excitatory-inhibitory imbalance. Despite this, NDD drug development programs targeting glutamate or gamma-aminobutyric acid (GABA) receptors have been largely unsuccessful. Nonetheless, recent drug trials in Rett syndrome (RTT), fragile X syndrome (FXS), and other NDDs targeting other mechanisms have met their endpoints. The purpose of this review is to identify the basis of these successful studies. Recent Findings Despite increasing evidence of disruption in synaptic homeostasis, most genetic variants associated with NDDs implicate proteins involved in cell regulation and not in neurotransmission. Metabolic processes, in particular mitochondrial function, appear to play a role in NDD pathophysiology. NDDs are also characterized by distinctive cell signaling abnormalities, which link cellular and synaptic homeostasis. Recent successful trials in NDDs, including those of trofinetide, the first drug specifically approved for one of these disorders (i.e., RTT), implicate the targeting of downstream processes (i.e., signaling pathways) rather than neurotransmitter receptors. Summary Recent positive drug studies in NDDs and their underlying mechanisms, in conjunction with new knowledge on the pathophysiology of these disorders, support the concept that targeting signaling and cellular and synaptic homeostasis may be a preferred approach for ameliorating synaptic abnormalities in many NDDs.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
ObjectType-Review-3
content type line 23
ISSN:1528-4042
1534-6293
1534-6293
DOI:10.1007/s11910-024-01394-3