GMP-grade human neural progenitors delivered subretinally protect vision in rat model of retinal degeneration and survive in minipigs.

BACKGROUND: Stem cell products are increasingly entering early stage clinical trials for treating retinal degeneration. The field is learning from experience about comparability of cells proposed for preclinical and clinical use. Without this, preclinical data supporting translation to a clinical study might not adequately reflect the performance of subsequent clinical-grade cells in patients. METHODS: Research-grade human neural progenitor cells (hNPC) and clinical-grade hNPC (termed CNS10-NPC) were injected into the subretinal space of the Royal College of Surgeons (RCS) rat, a rodent model of retinal degeneration such as retinitis pigmentosa. An investigational new drug (IND)-enabling study with CNS10-NPC was performed in the same rodent model. Finally, surgical methodology for subretinal cell delivery in the clinic was optimized in a large animal model with Yucatan minipigs. RESULTS: Both research-grade hNPC and clinical-grade hNPC can survive and provide functional and morphological protection in a dose-dependent fashion in RCS rats and the optimal cell dose was defined and used in IND-enabling studies. Grafted CNS10-NPC migrated from the injection site without differentiation into retinal cell phenotypes. Additionally, CNS10-NPC showed long-term survival, safety and efficacy in a good laboratory practice (GLP) toxicity and tumorigenicity study, with no observed cell overgrowth even at the maximum deliverable dose. Finally, using a large animal model with the Yucatan minipig, which has an eye size comparable to the human, we optimized the surgical methodology for subretinal cell delivery in the clinic. CONCLUSIONS: These extensive studies supported an approved IND and the translation of CNS10-NPC to an ongoing Phase 1/2a clinical trial (NCT04284293) for the treatment of retinitis pigmentosa.

Enhancing distress tolerance to uplift motivation in recovery: Results from an open development trial.

Objective: This open pilot study examines the feasibility, acceptability, and qualitative outcomes of an interactive web- and text message-delivered personalized feedback intervention aimed at cultivating motivation and tolerance of distress for adults initiating outpatient buprenorphine treatment. Methods: Patients (n = 10) initiating buprenorphine within the past 8 weeks first completed a web-based intervention focused on enhancing motivation and providing psychoeducation on distress tolerance skills. Participants then received 8 weeks of daily personalized text messages that provided reminders of salient motivational factors and recommended distress tolerance-oriented coping skills. Participants completed self-report measures to assess intervention satisfaction, perceived usability, and preliminary efficacy. Additional perspectives were captured via qualitative exit interviews. Results: In total, 100% of retained participants (n = 9) engaged with the text messages throughout the entire 8-week period. Mean scores of 27 (SD = 5.05) on the Client Satisfaction Questionnaire at the end of 8-week period indicated a high degree of satisfaction with the text-based intervention. The average rating on the System Usability Scale was 65.3 at the end of the 8-week program, suggesting that the intervention was relatively easy to use. Participants also endorsed positive experiences with the intervention during qualitative interviews. Clinical improvements were observed across the intervention period. Conclusions: Preliminary findings from this pilot suggest that the content and delivery method of this combined web- and text message-based personalized feedback intervention is perceived by patients as feasible and acceptable. Leveraging digital health platforms to augment buprenorphine has potential for high scalability and impact to reduce opioid use, increase adherence/retention to treatment, and prevent future incidence of overdose. Future work will evaluate the efficacy of the intervention in a randomized clinical trial design.

Feasibility and Acceptability of a Digital Health Intervention to Promote Continued Engagement in Medication for Opioid Use Disorder Following Release From Jail/Prison.

Background: Despite the extensive benefits of implementing Medications for Opioid Use Disorder (MOUD) in jail/prison, criminal justice-involved populations face significant challenges when transitioning back to the community following a period of incarceration. These risk factors are associated with increased drug use and discontinuation of evidence-based care. Novel intervention strategies are needed to support this high-risk period of transition. The primary objective of this protocol was to gather perspectives from the target population to optimize feasibility and acceptability of a combined in-person and text message-delivered intervention designed to support community reentry and continuation of MOUD. Methods: Participants (n = 8), who had prior experience engaging in MOUD while in jail/prison, were recruited from an outpatient primary care clinic in Rhode Island. A semi-structured interview was conducted to assess barriers/facilitators to technology following release, experiences of community reentry and OUD treatment, perceptions of continuum of care, and feasibility/acceptability of the intervention. All interviews were coded independently by 2 research assistants. Results: Participants reacted positively toward an intervention designed to support the transition to community-based care. Most participants denied any apprehension about using this type of platform. Obtaining a cell phone following release was endorsed as generally viable; however, special consideration must be paid to the consistency of cell phone service as well as digital literacy. Participants readily agreed on the utility of structured, daily text messages that provide motivational reminders and distress tolerance skill suggestions as well as the opportunity to access "on-demand" support. Conclusion: Overall, individuals engaged in MOUD while in jail/prison were receptive to a motivational- and distress tolerance-based digital health intervention to support recovery. Incorporating thematic results on suggested structural changes may increase the usability of this intervention to promote continuation of MOUD following release from jail/prison.