Critical Path Institute, Tucson, AZ, USA.
University of Birmingham, Birmingham, UK.
J Parkinsons Dis. 2021;11(s1):S103-S109. doi: 10.3233/JPD-202428.
The burden of Parkinson's disease (PD) continues to grow at an unsustainable pace particularly given that it now represents the fastest growing brain disease. Despite seminal discoveries in genetics and pathogenesis, people living with PD oftentimes wait years to obtain an accurate diagnosis and have no way to know their own prognostic fate once they do learn they have the disease. Currently, there is no objective biomarker to measure the onset, progression, and severity of PD along the disease continuum. Without such tools, the effectiveness of any given treatment, experimental or conventional cannot be measured. Such tools are urgently needed now more than ever given the rich number of new candidate therapies in the pipeline. Over the last decade, millions of dollars have been directed to identify biomarkers to inform progression of PD typically using molecular, fluid or imaging modalities. These efforts have produced novel insights in our understanding of PD including mechanistic targets, disease subtypes and imaging biomarkers. While we have learned a lot along the way, implementation of robust disease progression biomarkers as tools for quantifying changes in disease status or severity remains elusive. Biomarkers have improved health outcomes and led to accelerated drug approvals in key areas of unmet need such as oncology. Quantitative biomarker measures such as HbA1c a standard test for the monitoring of diabetes has impacted patient care and management, both for the healthcare professionals and the patient community. Such advances accelerate opportunities for early intervention including prevention of disease in high-risk individuals. In PD, progression markers are needed at all stages of the disease in order to catalyze drug development-this allows interventions aimed to halt or slow disease progression (very early) but also facilitates symptomatic treatments at moderate stages of the disease. Recently, attention has turned to the role of digital health technologies to complement the traditional modalities as they are relatively low cost, objective and scalable. Success in this endeavor would be transformative for clinical research and therapeutic development. Consequently, significant investment has led to a number of collaborative efforts to identify and validate suitable digital biomarkers of disease progression.
帕金森病（PD）的负担继续以不可持续的速度增长，尤其是因为它现在是增长最快的脑部疾病。尽管在遗传学和发病机制方面取得了重大发现，但许多 PD 患者常常需要数年时间才能获得准确的诊断，而且一旦得知自己患有该病，也无法知道自己的预后命运。目前，没有客观的生物标志物来衡量 PD 疾病连续体的发病、进展和严重程度。没有这些工具，就无法衡量任何特定治疗方法的有效性，无论是实验性的还是常规性的。鉴于目前有大量新的候选疗法正在研发中，因此现在比以往任何时候都更迫切需要这些工具。在过去的十年中，已经投入了数百万美元来确定生物标志物，以告知 PD 的进展，通常使用分子、液体或成像模式。这些努力为我们理解 PD 提供了新的见解，包括机械靶点、疾病亚型和成像生物标志物。虽然我们一路走来学到了很多，但将强大的疾病进展生物标志物作为衡量疾病状态或严重程度变化的工具仍然难以实现。生物标志物在许多尚未满足需求的关键领域（如肿瘤学）提高了健康结果并加速了药物批准。HbA1c 等定量生物标志物测量方法是监测糖尿病的标准测试，它影响了医疗保健专业人员和患者群体的患者护理和管理。这些进展加速了早期干预的机会，包括对高危人群的疾病预防。在 PD 中，需要在疾病的所有阶段都有进展标志物，以促进药物开发-这允许针对停止或减缓疾病进展（非常早期）的干预措施，但也为疾病的中度阶段提供对症治疗。最近，人们开始关注数字健康技术的作用，以补充传统模式，因为它们成本相对较低、客观且可扩展。在这方面的成功将对临床研究和治疗开发产生变革性影响。因此，大量投资已经导致了许多合作努力，以确定和验证合适的疾病进展数字生物标志物。
