Axons in the adult mammalian central nervous system (CNS) exhibit little regeneration after injury. It has been suggested that several axonal growth inhibitors prevent CNS axonal regeneration. Recent research has demonstrated that semaphorin3A (Sema3A) is one of the major inhibitors of axonal regeneration. We identified a strong and selective inhibitor of Sema3A, SM-216289, from the fermentation broth of a fungal strain. To examine the effect of SM-216289 in vivo, we transected the spinal cord of adult rats and administered SM-216289 into the lesion site for 4 weeks. Rats treated with SM-216289 showed substantially enhanced regeneration and/or preservation of injured axons, robust Schwann cell-mediated myelination and axonal regeneration in the lesion site, appreciable decreases in apoptotic cell number and marked enhancement of angiogenesis, resulting in considerably better functional recovery. Thus, Sema3A is essential for the inhibition of axonal regeneration and other regenerative responses after spinal cord injury (SCI). These results support the possibility of using Sema3A inhibitors in the treatment of human SCI.

SM-216289 (xanthofulvin) isolated from the fermentation broth of a fungal strain, Penicillium sp. SPF-3059, was identified as a strong semaphorin 3A (Sema3A) inhibitor. Sema3A-induced growth cone collapse of dorsal root ganglion neurons in vitro was completely abolished in the presence of SM-216289 at levels less than 2 M (IC 50 ‫؍‬ 0.16 M). When dorsal root ganglion explants were co-cultured with Sema3A-producing COS7 cells in a collagen gel matrix, SM-216289 enabled neurites to grow toward the COS7 cells. SM-216289 diminished the binding of Sema3A to its receptor neuropilin-1 in vitro, suggesting a direct interference of receptor-ligand association. Moreover, our data suggest that SM-216289 interacted with Sema3A directly and blocked the binding of Sema3A to its receptor. We examined the efficacy of SM-216289 in vivo using a rat olfactory nerve axotomy model, in which strong Sema3A induction has been reported around regenerating axons. The regeneration of olfactory nerves was significantly accelerated by a local administration of SM-216289 in the lesion site, suggesting the involvement of Sema3A in neural regeneration as an inhibitory factor. SM-216289 is an excellent molecular probe to investigate the function of Sema3A, in vitro and in vivo, and may be useful for the treatment of traumatic neural injuries.

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BackgroundDementia with Lewy bodies (DLB) is a progressive form of dementia, accompanied by a range of behavioural and psychological symptoms. The aim of this study was to identify current clinical practice for the treatment of DLB in Japan.MethodsWe conducted a survey of medical doctors engaged in the management of dementia in Japan. Participants were divided into two groups: psychiatrists (Group P) and neurologists or neurosurgeons (Group NS). Doctors completed a questionnaire and we analysed their responses to compare the two groups with regard to diagnosis and treatment of DLB, and in particular the treatment of behavioural and psychological symptoms of dementia (BPSD).ResultsResponses suggested that Group P conducted biomarker examinations less frequently and decided on their own therapeutic strategies more frequently than did Group NS. Both groups most frequently selected hallucinations/delusions as the symptoms given highest treatment priority. More than 70% of respondents in both groups reported having difficulties in treating BPSD. Atypical antipsychotics were more frequently prescribed by Group P, but were also prescribed in 70% of patients in Group NS. A third of patients received atypical antipsychotics for more than 1 year.ConclusionsThe responses to this survey highlighted the difficulties faced by clinicians managing patients with DLB and identified the need to effectively treat BPSD in such patients.

BackgroundWe performed a questionnaire survey of medical doctors engaged in the management of dementia to identify the actual status of treatment for dementia with Lewy bodies (DLB) in Japan.MethodsAmong participating medical doctors, we selected neurologists (Group N) and psychiatrists (Group P) because these physicians are usually involved in the management of DLB patients. The two groups were compared based on their diagnosis and treatment of DLB and in particular, parkinsonism.ResultsNeurological examinations and biomarker tests were less frequently performed by Group P than Group N. Antipsychotics and other psychotropics excluding anti‐dementia drugs were significantly more frequently administered by Group P than Group N. The proportion of physicians who selected l‐dopa as a first‐line therapy for parkinsonism was significantly higher in Group N than in Group P. Despite these between‐group differences, the following findings were common to the two groups: there was a discrepancy between the symptom that patients expressed the greatest desire to treat, and the awareness of physicians regarding the treatment of these symptoms; the initial agent was l‐dopa; and physicians exercised caution against the occurrence of hallucinations, delusions, and other adverse drug reactions.ConclusionsThe results of the present survey offer valuable insight for the formulation of future DLB therapeutic strategies.