Targeted genetic and molecular therapies in neurofibromatosis - A review of present therapeutic options and a glimpse into the future.

Neurofibromatosis type 1, the most common phakomatoses, can present with a host of signs and symptoms, usually involving the skin and the peripheral nervous system. It is characterized by a mutation in the neurofibromatosis type 1 gene on chromosome 17q11.2 that codes for the protein neurofibromin. Neurofibromin acts as a tumor suppressor gene by inhibiting rat sarcoma (Ras) activity and its deficiency leads to increased Ras activity, cellular proliferation and tumor formation. This review was conducted to analyze the various targeted therapies at the genetic and molecular level employed to manage the tumors and other clinical presentations associated with neurofibromatosis type 1. Twenty-eight studies of treatment modalities for the conditions associated with neurofibromatosis and which involved either targeted gene therapy or molecular level therapies, including the latest advances, were included in this review. Mitogen-activated protein kinase kinase inhibition, mammalian target of Rapamycin inhibition and Tyrosine kinase inhibition, represent some of the newer treatment options in this category. Although there are a number of trials for providing therapeutic options at the genetic and molecular level for the various physical and psychological morbidities associated with neurofibromatosis type 1, most of them are in the preclinical stage. Increased clinical trials of the molecules and gene therapies could significantly help in managing the various chronic and sometimes, life-threatening conditions associated with neurofibromatosis 1 and these will probably represent the preferred treatment direction of the future.

Cognitive function and activities of daily living in people affected by leprosy: A cross-sectional, population-based, case-control study.

OBJECTIVES: There has been controversy regarding whether or not people affected by leprosy have more cognitive dysfunction than healthy individuals. The purpose of this study was to assess cognitive functions and activities of daily living (ADL) in people affected by leprosy relative to a control population living in rural areas. MATERIALS AND METHODS: We assessed cognitive functions and ADL using the Korean Mini-Mental State Examination (K-MMSE), Korean Dementia Screening Questionnaire (KDSQ), and Seoul-Instrumental ADL (S-IADL). Higher scores of K-MMSE and lower scores of both KDSQ and S-IADL are indicative of better functioning. We assessed 224 persons living in Sorokdo who were affected by leprosy and 448 age- and gender-matched control subjects living in Namwon of the Chonbuk province. RESULTS: After adjusting for age, gender, and educational status, the K-MMSE score was found to be significantly higher in people affected by leprosy than in control subjects (23.14 ± 4.89 vs. 22.25 ± 4.62, respectively, P = 0.022). Items related to memory in the KDSQ showed no differences between the groups, but people affected by leprosy had a better score in division for other cognitive functions than controls. On items related to ADL in the KDSQ and S-IADL, people affected by leprosy performed significantly worse compared with controls. CONCLUSIONS: Our results suggest that although people affected by leprosy have a lower capacity of ADL, they may have better cognitive functions than normal controls.