RARE DISEASE
Atypical autism
Atypical autism
Atypical autism
Drug discovery
1
drug
With orphan designation
Overview
Atypical Autism Overview
Atypical autism (PDD-NOS/DSM-IV term, now classified under ASD per DSM-5) presents with social-communication deficits and restricted/repetitive behaviors but does not meet full criteria for classic autism. Symptoms may emerge later or show atypical patterns, such as milder social challenges or isolated sensory sensitivities. Early diagnosis and personalized interventions (e.g., behavioral, speech, and occupational therapies) are critical for improving functional outcomes [1][3][6][11].
Therapies
Behavioral: Applied Behavior Analysis (ABA) for skill development and behavior modification [1][8][13].
Multidisciplinary: Speech therapy (language deficits), occupational therapy (sensory/motor skills), and social skills training [3][6][8].
Adjunctive: Limited pharmacotherapy (e.g., SSRIs for anxiety; risperidone for aggression) [1][3][18].
Categories: rare genetic diseases, rare neurological diseases
Research Papers
741 drug discovery papers related to Atypical autism, with 3 first-in-class and 5 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
741 drug discovery papers related to Atypical autism, with 3 first-in-class and 5 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-18 | Endothelial Dysfunction and Neurovascular Alterations in Autism Spectrum Disorder.
The traditional view of autism spectrum disorder (ASD) has largely focused on neuronal mechanisms as the primary drivers of atypical neurodevelopment. However, increasing evidence suggests that vascular and neurovascular processes also contribute to the developmental trajectories associated with the condition. In particular, endothelial cells have emerged as active regulators of brain development through their roles in angiogenesis, blood-brain barrier (BBB) formation, neurovascular signaling, and interactions with the immune system. This chapter examines the growing body of evidence supporting a neurovascular perspective of ASD, in which endothelial dysfunction is considered a biologically meaningful component of pathophysiology rather than a secondary consequence of neural alterations. Evidence from both human studies and experimental models indicates that disturbances in vascular development, BBB integrity, VEGF signaling, endothelial metabolism, and neuroimmune communication can influence brain maturation and behavior. Particular attention is given to prenatal and perinatal factors, including maternal inflammation, placental dysfunction, and environmental exposures that affect endothelial development during critical periods of neurodevelopment. The chapter also explores the contribution of oxidative and nitrosative stress, endothelial adhesion molecules, and the neurovascular unit as mechanisms linking vascular and neural dysfunction. By integrating findings across molecular, cellular, developmental, and systems-level studies, this work advances a framework in which vascular and neural processes are tightly interconnected throughout brain development. This perspective not only provides new insight into the biological heterogeneity of ASD but also highlights the endothelium and the neurovascular unit as promising targets for biomarker discovery and future therapeutic intervention.
2026-06-04 | Olfactory Valence-Processing Deficits and Aberrant Brain Network Connectivity Underlie Social Dysfunction in Shank3-/- ASD Model Mice.
Olfaction is crucial for rodent social behavior, and olfactory dysfunction has been observed in multiple autism spectrum disorder (ASD) models, but its phenotype in Shank3⁻/⁻ mice (a classic ASD model) remains unclear. We systematically assessed olfactory function in Shank3⁻/⁻ mice by using a modified olfactory three-chamber test and optimized ultrasonic vocalization (USV) detection in combination with resting-state functional magnetic resonance imaging (rs-fMRI), whole-brain c-Fos mapping, and three-dimensional (3D) behavioral analysis. Our results showed abnormal odor preference and hyperconnectivity in olfaction-associated brain networks. Upon exposure to neutral, appetitive, and social pheromone odors, Shank3⁻/⁻ mice displayed atypical whole-brain c-Fos activation patterns, which were coupled with synchronized locomotor suppression and stereotyped behaviors. This study maps the neural-behavioral responses to odors in Shank3-/- mice, linking olfactory deficits to autism-like behaviors, and highlights the olfactory system as a targetable pathway for sensory-based autism therapies.
2026-05-11 | Risperidone redefined: A three-decade odyssey of broadening indications and evolving formulations.
Risperidone, one of the most widely prescribed second-generation antipsychotics globally, is distinguished by its broad therapeutic utility and adaptable formulation strategies. It was the second atypical antipsychotic introduced after clozapine and its pharmacological profile was characterized by potent antagonism of dopamine D2 and serotonin 5HT2A receptors. It provided more effective management of positive, negative, and mood symptoms across psychiatric disorders while minimizing extrapyramidal side effects compared to first-generation agents. Since its introduction, risperidone's indications have expanded significantly to encompass schizophrenia, bipolar I disorder, and autism-related irritability across diverse age groups from children aged five years to older adults. This therapeutic breadth is matched by remarkable formulation versatility, beginning with oral tablets and liquid syrup, progressing to intramuscular depot injections, and most recently culminating in subcutaneous extended-release formulations approved in 2018, 2023, and 2025. These innovations address critical challenges in psychiatric care, particularly medication adherence, by offering flexible dosing intervals and eliminating the need for oral supplementation in newer formulations. This article provides a comprehensive review of risperidone's basic pharmacology, its evolving landscape of Food and Drug Administration-approved and off-label indications, the transformative journey from oral to long-acting injectable formulations, and the complex interplay among drug attitudes, patient perceptions, and treatment acceptance.
2026-06-18 | Endothelial Dysfunction and Neurovascular Alterations in Autism Spectrum Disorder.
The traditional view of autism spectrum disorder (ASD) has largely focused on neuronal mechanisms as the primary drivers of atypical neurodevelopment. However, increasing evidence suggests that vascular and neurovascular processes also contribute to the developmental trajectories associated with the condition. In particular, endothelial cells have emerged as active regulators of brain development through their roles in angiogenesis, blood-brain barrier (BBB) formation, neurovascular signaling, and interactions with the immune system. This chapter examines the growing body of evidence supporting a neurovascular perspective of ASD, in which endothelial dysfunction is considered a biologically meaningful component of pathophysiology rather than a secondary consequence of neural alterations. Evidence from both human studies and experimental models indicates that disturbances in vascular development, BBB integrity, VEGF signaling, endothelial metabolism, and neuroimmune communication can influence brain maturation and behavior. Particular attention is given to prenatal and perinatal factors, including maternal inflammation, placental dysfunction, and environmental exposures that affect endothelial development during critical periods of neurodevelopment. The chapter also explores the contribution of oxidative and nitrosative stress, endothelial adhesion molecules, and the neurovascular unit as mechanisms linking vascular and neural dysfunction. By integrating findings across molecular, cellular, developmental, and systems-level studies, this work advances a framework in which vascular and neural processes are tightly interconnected throughout brain development. This perspective not only provides new insight into the biological heterogeneity of ASD but also highlights the endothelium and the neurovascular unit as promising targets for biomarker discovery and future therapeutic intervention.
2026-06-04 | Olfactory Valence-Processing Deficits and Aberrant Brain Network Connectivity Underlie Social Dysfunction in Shank3-/- ASD Model Mice.
Olfaction is crucial for rodent social behavior, and olfactory dysfunction has been observed in multiple autism spectrum disorder (ASD) models, but its phenotype in Shank3⁻/⁻ mice (a classic ASD model) remains unclear. We systematically assessed olfactory function in Shank3⁻/⁻ mice by using a modified olfactory three-chamber test and optimized ultrasonic vocalization (USV) detection in combination with resting-state functional magnetic resonance imaging (rs-fMRI), whole-brain c-Fos mapping, and three-dimensional (3D) behavioral analysis. Our results showed abnormal odor preference and hyperconnectivity in olfaction-associated brain networks. Upon exposure to neutral, appetitive, and social pheromone odors, Shank3⁻/⁻ mice displayed atypical whole-brain c-Fos activation patterns, which were coupled with synchronized locomotor suppression and stereotyped behaviors. This study maps the neural-behavioral responses to odors in Shank3-/- mice, linking olfactory deficits to autism-like behaviors, and highlights the olfactory system as a targetable pathway for sensory-based autism therapies.
2026-05-11 | Risperidone redefined: A three-decade odyssey of broadening indications and evolving formulations.
Risperidone, one of the most widely prescribed second-generation antipsychotics globally, is distinguished by its broad therapeutic utility and adaptable formulation strategies. It was the second atypical antipsychotic introduced after clozapine and its pharmacological profile was characterized by potent antagonism of dopamine D2 and serotonin 5HT2A receptors. It provided more effective management of positive, negative, and mood symptoms across psychiatric disorders while minimizing extrapyramidal side effects compared to first-generation agents. Since its introduction, risperidone's indications have expanded significantly to encompass schizophrenia, bipolar I disorder, and autism-related irritability across diverse age groups from children aged five years to older adults. This therapeutic breadth is matched by remarkable formulation versatility, beginning with oral tablets and liquid syrup, progressing to intramuscular depot injections, and most recently culminating in subcutaneous extended-release formulations approved in 2018, 2023, and 2025. These innovations address critical challenges in psychiatric care, particularly medication adherence, by offering flexible dosing intervals and eliminating the need for oral supplementation in newer formulations. This article provides a comprehensive review of risperidone's basic pharmacology, its evolving landscape of Food and Drug Administration-approved and off-label indications, the transformative journey from oral to long-acting injectable formulations, and the complex interplay among drug attitudes, patient perceptions, and treatment acceptance.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Atypical autism.
1 orphan drug designation for Atypical autism.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Fluoxetine | small molecules | FDA | 1999-04-30 | — | Neuropharm, Ltd. |
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