Genetic influences on response to gait rehabilitation in Parkinson’s disease

2003年人类基因组计划的完成标志着基因组时代的开始， “个性化”（精准）医疗的诞生。在过去的十年里，遗传学提供了一个新的 了解预测，诊断和治疗个人健康状况。的确， 精准医疗已经开始影响几乎所有的医学领域，具有巨大的潜力， 影响身体康复的时间、剂量和强度。 这项研究的长期目标是：（1）确定是否与某些遗传变异相关， 学习障碍会影响运动和认知的好处， 帕金森病（PD）退伍军人的康复，以及（2）使用这些知识来识别 可能需要针对其基因型制定康复策略的患者亚群， 优化身体康复。为了实现这些目标，我们将在10周内招募30名PD退伍军人 中等强度的步态训练计划，包括每周2次跑步机训练， 步态质量的线索。目的1将研究已知影响人类免疫功能的两个基因中的变异体之间的关联。 认知和运动学习（APOE-104和BDNF-Met 66），以及步态训练后的运动改善。 具体而言，训练期间和训练后的步行变化将敏感而客观地 使用最先进的定量步态分析进行评估，并比较三种基因型 组（BDNF-Met 66的携带者（N=10）、APOE-β 4的携带者（N=10）和不携带BDNF-Met 66的携带者（N =10）、APOE-β 4的携带者（N=10）和不携带BDNF-Met 66的携带者（N=10））。 这些变体（N=10））。目的2将检测APOE-104和BDNF-Met 66遗传变异体对人肝癌细胞的影响。 认知的变化。为了做到这一点，我们将测量认知 使用旨在评估注意力的简短、有针对性的电池进行训练前和训练后的表现， 处理速度、执行功能和学习/记忆，这些领域受到的影响更大， 可能会改善PD的体育锻炼。我们将测试的假设，退伍军人与PD谁 携带APOE-β 4或BDNF-Met 66等位基因的人将表现出步态的较小改善（目标1）， 认知（目标2），以响应为期10周的步态训练计划。总的来说，该项目的成果将 增强我们对不同遗传特征对身体反应的影响的认识， 患有PD的退伍军人的康复，并将生成支持数据，这些数据将转化为更多信息 为PD患者提供个性化和有效的康复计划。

The completion of the Human Genome Project in 2003 marked the beginning of the genomic era and the birth of “personalized” (precision) medicine. In the last decade, genetics have provided a new understanding of predicting, diagnosing, and treating individual health conditions. Indeed, such precision medicine has begun to impact virtually all areas of medicine, with significant potential to influence the timing, dosage, and intensity of physical rehabilitation. The long-term goals of this research are: (1) to determine if certain genetic variants associated to learning impairments impact the motor and cognitive benefit experienced in response to physical rehabilitation in Veterans with Parkinson's disease (PD), and (2) to use that knowledge to identify subpopulations of patients that may require rehabilitative strategies tailored to their genotype to optimize physical rehabilitation. To achieve these goals we will enroll 30 Veterans with PD in a 10-week moderate intensity gait training program consisting of 2 times per week treadmill training with verbal cues for gait quality. Aim 1 will examine the association between variants in 2 genes known to affect cognition and motor learning (APOE-ɛ4 and BDNF-Met66), and motor improvements after gait training. Specifically, changes in walking from during and after training will be sensitively and objectively assessed using state-of-the-art quantitative gait analysis, and compared between three genotype groups (carriers of BDNF-Met66 (N=10), carriers of APOE-ɛ4 (N=10) and those not carrying either of those variants (N=10)). Aim 2 will examine the effect of APOE-ɛ4 and BDNF-Met66 genetic variants on cognitive changes in response to this training program. In order to do this we will measure cognitive performance pre- and post-training using a brief, targeted battery aimed at assessing attention, processing speed, executive function, and learning/memory, the domains more affected, and more likely to improve with physical exercise in PD. We will test the hypothesis that Veterans with PD who carry an APOE-ɛ4 or BDNF-Met66 allele will demonstrate smaller improvements in gait (Aim 1) and cognition (Aim 2) in response to a 10-week gait training program. Overall the results of this project will enhance our knowledge regarding the influence of different genetic profiles in the response to physical rehabilitation in Veterans with PD, and will generate supporting data that will translate to more personalized and effective rehabilitation programs for people with PD.