Investigational drugs in early-stage clinical trials for autism spectrum disorder

ABSTRACT

Introduction: Pharmacologic interventions in Autism Spectrum Disorder (ASD) have historically focused on symptom-based approaches. However, a treatment for the core social deficits has remained unidentified. While a definitive theory for the cause of ASD is not yet known, recent advances in our understanding of ASD pathophysiology have opened the door for research on new pharmaceutical methods to target core symptomology.

Areas covered: Herein, we review the novel pharmacologic therapies undergoing early-stage clinical trials for the treatment of the social symptoms associated with ASD. Specifically, these strategies center on altering neurologic excitatory and inhibitory imbalance, neuropeptide abnormalities, immunologic dysfunction, and biochemical deficiencies in ASD.

Expert opinion: Utilizing the growing field of knowledge regarding the pathological mechanisms and altered neurobiology of individuals with ASD has led to the development of many innovative pharmaceutical interventions. Clinical trials for neurobiologic and immunologic targets show promise in impacting the social behavior and processing deficits in ASD but need evaluation in larger clinical trials and continued biomarker development to more effectively and consistently assess pharmacologic effects. Additionally, evaluating patient-specific drug responsivity and integrating behavioral intervention in conjunction with pharmacologic treatment is crucial to developing a successful approach to ASD treatment.

Trial registration: ClinicalTrials.gov identifier: NCT00872898.

Trial registration: ClinicalTrials.gov identifier: NCT01333865.

Trial registration: ClinicalTrials.gov identifier: NCT01086475.

Trial registration: ClinicalTrials.gov identifier: NCT00198120.

Trial registration: ClinicalTrials.gov identifier: NCT01813318.

Trial registration: ClinicalTrials.gov identifier: NCT02611921.

Trial registration: ClinicalTrials.gov identifier: NCT01288716.

Trial registration: ClinicalTrials.gov identifier: NCT01078714.

Trial registration: ClinicalTrials.gov identifier: NCT01881737.

Trial registration: ClinicalTrials.gov identifier: NCT02081027.

Trial registration: ClinicalTrials.gov identifier: NCT01944046.

Trial registration: ClinicalTrials.gov identifier: NCT02901431.

Trial registration: ClinicalTrials.gov identifier: NCT01793441.

Trial registration: ClinicalTrials.gov identifier: NCT01474278.

Trial registration: ClinicalTrials.gov identifier: NCT02176317.

Trial registration: ClinicalTrials.gov identifier: NCT02508259.

Trial registration: ClinicalTrials.gov identifier: NCT00627705.

Trial registration: ClinicalTrials.gov identifier: NCT00786799.

Trial registration: ClinicalTrials.gov identifier: NCT01474993.

Trial registration: ClinicalTrials.gov identifier: NCT02909959.

Trial registration: ClinicalTrials.gov identifier: NCT01039792.

Trial registration: ClinicalTrials.gov identifier: NCT03771560.

KEYWORDS:

• Autism
• clinical trials
• drug development
• social deficits

Article highlights

• While pharmacologic interventions in Autism Spectrum Disorder (ASD) have historically focused on symptom-based approaches, novel therapeutic targets aim for a treatment of the core social deficits in ASD

• Novel pharmacologic approaches targeting the core social deficits of ASD have focused on neural excitatory-to-inhibitory imbalance, neuropeptide abnormalities, immunologic dysfunction, and biochemical deficiencies

• New drugs show promise but have had inconsistent findings likely due to variability in group demographics, symptom heterogeneity, and outcome evaluation

• Identifying subgroups of persons with ASD who may respond best to a new treatment in development may be essential to success in this field given the heterogeneity of ASD

• Future studies must aim to evaluate drug responsivity, advance outcome measure methodology, and integrate behavioral interventions to continue to advance pharmacotherapy research in ASD

• Steps to address high placebo response rates in ASD will likely include increasing reliance on quantitative outcome measures and use of quantitative measures of pathophysiology to serve as early signs of effective target engagement

• Success in ASD treatment development may require acceptance by regulatory agencies of outcome measure approaches that differ from past work involved with the approval of drugs targeting irritability associated with ASD

This box summarizes the key points contained in the article.

Declaration of interest

C Erickson is the inventor on patents held by Indiana University and Cincinnati Children’s Hospital related to neurodevelopmental disorder treatment. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.