Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome
Abstract Background Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like grow...
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Molecular Autism |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13229-022-00493-7 |
| _version_ | 1819209990256197632 |
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| author | A. Kolevzon M. S. Breen P. M. Siper D. Halpern Y. Frank H. Rieger J. Weismann M. P. Trelles B. Lerman R. Rapaport J. D. Buxbaum |
| author_facet | A. Kolevzon M. S. Breen P. M. Siper D. Halpern Y. Frank H. Rieger J. Weismann M. P. Trelles B. Lerman R. Rapaport J. D. Buxbaum |
| author_sort | A. Kolevzon |
| collection | DOAJ |
| description | Abstract Background Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like growth factor-1 (IGF-1) in PMS, this study aims to follow-up a previous pilot study with IGF-1 to further evaluate this novel therapeutic for core symptoms of ASD in children with PMS. Methods Ten children aged 5–9 with PMS were enrolled. Participants were randomized to receive IGF-1 or placebo (saline) using a 12-week, double-blind, crossover design. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist—Social Withdrawal (ABC-SW) subscale as well as secondary outcome measures reflecting core symptoms of ASD. To increase power and sample size, we jointly analyzed the effect of IGF-1 reported here together with results from our previous controlled trail of IGF-1 in children with PMS (combined N = 19). Results Results on the ABC-SW did not reach statistical significance, however significant improvements in sensory reactivity symptoms were observed. In our pooled analyses, IGF-1 treatment also led to significant improvements in repetitive behaviors and hyperactivity. There were no other statistically significant effects seen across other clinical outcome measures. IGF-1 was well tolerated and there were no serious adverse events. Limitations The small sample size and expectancy bias due to relying on parent reported outcome measures may contribute to limitations in interpreting results. Conclusion IGF-1 is efficacious in improving sensory reactivity symptoms, repetitive behaviors, and hyperactivity in children with PMS. Trial registration NCT01525901. |
| first_indexed | 2024-12-23T06:04:03Z |
| format | Article |
| id | doaj.art-4ca558e55eab463a8b97251db93a455c |
| institution | Directory Open Access Journal |
| issn | 2040-2392 |
| language | English |
| last_indexed | 2024-12-23T06:04:03Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Autism |
| spelling | doaj.art-4ca558e55eab463a8b97251db93a455c2022-12-21T17:57:36ZengBMCMolecular Autism2040-23922022-04-011311510.1186/s13229-022-00493-7Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndromeA. Kolevzon0M. S. Breen1P. M. Siper2D. Halpern3Y. Frank4H. Rieger5J. Weismann6M. P. Trelles7B. Lerman8R. Rapaport9J. D. Buxbaum10Seaver Autism Center for Research and TreatmentSeaver Autism Center for Research and TreatmentSeaver Autism Center for Research and TreatmentSeaver Autism Center for Research and TreatmentSeaver Autism Center for Research and TreatmentSeaver Autism Center for Research and TreatmentSeaver Autism Center for Research and TreatmentSeaver Autism Center for Research and TreatmentSeaver Autism Center for Research and TreatmentDepartment of Pediatrics, Icahn School of Medicine at Mount SinaiSeaver Autism Center for Research and TreatmentAbstract Background Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like growth factor-1 (IGF-1) in PMS, this study aims to follow-up a previous pilot study with IGF-1 to further evaluate this novel therapeutic for core symptoms of ASD in children with PMS. Methods Ten children aged 5–9 with PMS were enrolled. Participants were randomized to receive IGF-1 or placebo (saline) using a 12-week, double-blind, crossover design. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist—Social Withdrawal (ABC-SW) subscale as well as secondary outcome measures reflecting core symptoms of ASD. To increase power and sample size, we jointly analyzed the effect of IGF-1 reported here together with results from our previous controlled trail of IGF-1 in children with PMS (combined N = 19). Results Results on the ABC-SW did not reach statistical significance, however significant improvements in sensory reactivity symptoms were observed. In our pooled analyses, IGF-1 treatment also led to significant improvements in repetitive behaviors and hyperactivity. There were no other statistically significant effects seen across other clinical outcome measures. IGF-1 was well tolerated and there were no serious adverse events. Limitations The small sample size and expectancy bias due to relying on parent reported outcome measures may contribute to limitations in interpreting results. Conclusion IGF-1 is efficacious in improving sensory reactivity symptoms, repetitive behaviors, and hyperactivity in children with PMS. Trial registration NCT01525901.https://doi.org/10.1186/s13229-022-00493-7Phelan-McDermid syndromePMSshank3Autism spectrum disorderASDInsulin-like growth factor-1 |
| spellingShingle | A. Kolevzon M. S. Breen P. M. Siper D. Halpern Y. Frank H. Rieger J. Weismann M. P. Trelles B. Lerman R. Rapaport J. D. Buxbaum Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome Molecular Autism Phelan-McDermid syndrome PMS shank3 Autism spectrum disorder ASD Insulin-like growth factor-1 |
| title | Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome |
| title_full | Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome |
| title_fullStr | Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome |
| title_full_unstemmed | Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome |
| title_short | Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome |
| title_sort | clinical trial of insulin like growth factor 1 in phelan mcdermid syndrome |
| topic | Phelan-McDermid syndrome PMS shank3 Autism spectrum disorder ASD Insulin-like growth factor-1 |
| url | https://doi.org/10.1186/s13229-022-00493-7 |
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