Cell Therapy in Huntington's Disease

Summary: Huntington''s disease is an autosomal dominant genetic disease, which results in progressive neuronal degeneration in the neostriatum and neocortex, and associated functional impairments in motor, cognitive, and psychiatric domains. Although the genetic mutation is identified, involving an abnormal CAG expansion within the htt gene on chromosome 4, the mechanism by which this leads to neuronal cell death and the question of why striatal neurones are targeted both remain unknown. Thus, in addition to the search for molecular and genetic strategies to inhibit development of the disease, we still need to identify effective strategies for cellular repair in affected individuals. Aspects of the human neuropathology can be well modeled by excitotoxic or metabolic lesions in experimental animals, and in transgenic mice carrying the htt mutation, providing the basis for testing alternative therapeutic strategies. The rationale and efficacy of alternative cell therapies are reviewed, including transplantation repair with embryonic striatal tissues, expansion and differentiation of striatal-like cells from stem cells, and in vivo and ex vivo gene therapy for delivery of neuroprotective growth factor molecules. Pilot and experimental clinical trials of several approaches are now also underway, and the alternative strategies are compared.     

Cultural beliefs about TBI in Botswana

Cultural differences have been shown to have an influence on outcome following traumatic brain injury (TBI). This study examined illness representations and the nature of beliefs about TBI in Botswana, a small middle income country in southern Africa. Participants included 26 people who had sustained moderate to severe TBI, 18 caregivers (all significant others) and 27 healthcare workers. A mixed-methods approach was utilised. Illness representations were assessed using the revised Illness Perception Questionnaire (IPQ-R), and beliefs and perceptions about cause of injury were established through semi-structured qualitative interviews. Results indicated that participants considered TBI to be chronic in nature and accompanied by serious consequences. Participants held positive attitudes about the manageability of symptoms despite having little understanding about TBI and its consequences. People with TBI tended to report fewer symptoms than did their caregivers. In addition, although some participants held concrete beliefs about the causes of injury, many participants attributed the injury to supernatural causes. Religious interpretations were also commonly held. Although age appeared to be associated with beliefs, no significant relationships existed between demographic factors and beliefs about the injury. This study highlights the importance of understanding the cultural perspectives of patients and their families in order to provide effective care.     

“A good spot”: Health promotion discourse,healthy cities and heterogeneity in contemporary Denmark

Health promotion at a community level has gained popularity in recent decades within and outside academic environments. The health promotion discourse is part of a wider political discourse, aimed at empowering individuals to take control of their own lives and enabling them to be engaged, responsible and active citizens in their own communities. Key values of the discourse, deriving from a democratic and individualistic culture, are evident in how local authorities develop and implement policies aimed at promoting population health and wellbeing. In this article, we draw on data from a relatively poor multicultural Danish community incorporated in the WHO Healthy Cities Programme. We explore how key terms of the health promoting discourse are constructed, operationalized and resisted by different subgroups. The contradictions that emerge challenge how we comprehend communities in relation to safety and harmony, and how people within defined communities are involved in common community life.     

Cefixime in the treatment of uncomplicated gonorrhea.

One hundred consecutive patients with uncomplicated gonorrhea were treated with 800 mg of cefixime. Follow-up evaluation was obtained for 73 patients, and at that time 71 of the 73 had negative culture results for Neisseria gonorrhoeae. Minimal adverse side effects were reported. Cefixime 800 mg appears to be an excellent treatment for uncomplicated gonorrhea.     

Embryonic striatal grafts restore bi‐directional synaptic plasticity in a rodent model of Huntington’s disease

Embryonic striatal grafts integrate with the host striatal circuitry, forming anatomically appropriate connections capable of influencing host behaviour. In addition, striatal grafts can influence host behaviour via a variety of non‐specific, trophic and pharmacological mechanisms; however, direct evidence that recovery is dependent on circuit reconstruction is lacking. Recent studies suggest that striatal grafts alleviate simple motor deficits, and also that learning of complex motor skills and habits can also be restored. However, although the data suggest that such ‘re‐learning’ requires integration of the graft into the host striatal circuitry, little evidence exists to demonstrate that such integration includes functional synaptic connections. Here we demonstrate that embryonic striatal grafts form functional connections with the host striatal circuitry, capable of restoring stable synaptic transmission, within an excitotoxic lesion model of Huntington’s disease. Furthermore, such ‘functional integration’ of the striatal graft enables the expression of host–graft bi‐directional synaptic plasticity, similar to the normal cortico‐striatal circuit. These results indicate that striatal grafts express synaptic correlates of learning, and thereby provide direct evidence of functional neuronal circuit repair, an essential component of ‘functional integration’.