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和 “个性化”(精准)医学的诞生。在过去的十年里，遗传学提供了一种新的 了解个人健康状况的预测、诊断和治疗。的确，这样的 精准医学已经开始影响几乎所有的医学领域，具有巨大的潜力 影响身体康复的时机、剂量和强度。 这项研究的长期目标是：(1)确定某些遗传变异是否与 学习障碍对运动和认知方面的益处产生影响 帕金森氏病(PD)退伍军人的康复，以及(2)使用这一知识来识别 可能需要针对其基因型量身定制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名患有PD的退伍军人 中等强度的步态训练计划，包括每周两次的跑步机训练和口头训练 步态质量的提示。目标1将检查两个已知影响基因的变异之间的联系 认知和运动学习(APOE-ɛ4和BDNFME66)，以及步态训练后的运动改善。 具体地说，训练期间和训练后步行的变化将是敏感和客观的 使用最先进的定量步态分析进行评估，并在三种基因型之间进行比较 组(BDNFMet66携带者(N=10)、APOE-ɛ4携带者(N=10)和未携带 这些变异体(N=10)。目的2将研究载脂蛋白E-ɛ4和脑源性神经营养因子-Met66的遗传变异对 这一培训计划带来的认知变化。为了做到这一点，我们将测量认知 在训练前和训练后使用简短的、有针对性的电池来评估注意力， 处理速度、执行功能和学习/记忆，这些领域受影响更大，而且更多 在帕金森病患者中进行体育锻炼可能会有所改善。我们将检验这样一个假设，患有PD的退伍军人 携带ApoE-ɛ4或BDNFMet66等位基因将显示出较小的步态改善(目标1)和 认知(目标2)，回应为期10周的步态训练计划。总体而言，该项目的成果将 增强我们对不同基因类型在物理反应中的影响的知识 对患有帕金森病的退伍军人进行康复，并将产生支持数据，这些数据将转化为更多 为帕金森病患者提供个性化和有效的康复方案。

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.