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Tay-Sachs disease (TSD) is an inherited neurological disorder caused by deficiency of hexosaminidase A (HexA). Here, we describe an adeno-associated virus (AAV) gene therapy expanded-access trial in two patients with infantile TSD (IND 18225) with safety as the primary endpoint and no secondary endpoints. Patient TSD-001 was treated at 30 months with an equimolar mix of AAVrh8-HEXA and AAVrh8-HEXB administered intrathecally (i.t.), with 75% of the total dose (1 × 10

Background Pharmacy-based interventions are complex public health endeavors which include, but are not restricted to, the conventional medication supply role. In diabetes, such interventions may improve patients’ outcomes. The aim of this study was to review relevant policies and research developed in Portugal directed at pharmacy-based diabetes interventions, and to inform future policies, practice and research in collaborative practice with primary care. Research method An exploratory review of diabetes legislation and policy papers, as well as a comprehensive review in Embase, MEDLINE (via Ovid and PubMed), Google Scholar, and grey literature until November 2017 was performed. Results Sixteen policy papers and 10 studies were included in the analysis. Positive evidence from pharmacy interventions was retrieved concerning screening individuals at risk, screening uncontrolled patients, managing diabetes, and supporting self-monitoring. Conclusions Some consistency in favorable findings, but also room for improvements in health policies, intervention design and research methods, were observed. Electronic supplementary material The online version of this article (10.1186/s40545-019-0166-1) contains supplementary material, which is available to authorized users.

Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by extracellular deposition of amyloid fibrils composed by mutated transthyretin (TTR) mainly in the peripheral nervous system. At present, liver transplantation is still the standard treatment to halt the progression of clinical symptoms in FAP, but new therapeutic strategies are emerging, including the use of TTR stabilizers. Here we propose to establish a new gene therapy approach using adeno-associated virus (AAV) vectors to deliver the trans-suppressor TTR T119M variant to the liver of transgenic TTR V30M mice at different ages. This TTR variant is known for its ability to stabilize the tetrameric protein. Analysis of the gastrointestinal tract of AAV-treated animals revealed a significant reduction in deposition of TTR non-fibrillar aggregates in as much as 34% in stomach and 30% in colon, as well as decreased levels of biomarkers associated with TTR deposition, namely the endoplasmic reticulum stress marker BiP and the extracellular matrix protein MMP-9. Moreover, we showed with different studies that our approach leads to an increase in tetrameric and more stable forms of TTR, in favor of destabilized monomers. Altogether our data suggest the possibility to use this gene therapy approach in a prophylactic manner to prevent FAP pathology.