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Review
. 2024 May 6:5:26330040241249189.
doi: 10.1177/26330040241249189. eCollection 2024 Jan-Dec.

Establishing resources and increasing awareness to advance research on Dentatorubral-pallidoluysian atrophy toward a treatment: a patient organization perspective

Silvia Prades  1   2 , Andrea Compton  2 , Jeffrey B Carroll  2   3
Affiliations
Review

Establishing resources and increasing awareness to advance research on Dentatorubral-pallidoluysian atrophy toward a treatment: a patient organization perspective

Silvia Prades et al. Ther Adv Rare Dis. .

Abstract

Dentatorubral-pallidoluysian atrophy (DRPLA) is an ultra-rare neurodegenerative disorder characterized by ataxia, cognitive decline, myoclonus, chorea, epilepsy, and psychiatric manifestations. This article delves into the multifaceted efforts of CureDRPLA, a family-driven non-profit organization, in advancing research, raising awareness, and developing therapeutic strategies for this complex condition. CureDRPLA's inception in 2019 led to the establishment of the DRPLA Research Program, and since then have funded research projects to advance the understanding of DRPLA including but not limited to human cellular and mouse models, a natural history and biomarkers study, and a patient registry. There are currently no disease-modifying treatments for DRPLA, motivating a concerted effort on behalf of CureDRPLA to hasten their development by funding and coordinating preclinical studies of therapies in multiple modalities. Of particular interest are therapies focused on lowering the expression (or downregulation) of ATN1, the mutant gene that causes DRPLA, in hopes of tackling the pathology at its root. As with many ultra-rare diseases, a key challenge in DRPLA remains the complexity of coordinating both basic and clinical research efforts across multiple sites around the world. Finally, despite the generous financial support provided by CureDRPLA, more funding and collective efforts are still required to advance research toward the clinic and develop effective treatments for individuals with DRPLA.

Keywords: DRPLA; drug development; patient advocacy group; polyQ repeat disorders; rare diseases; research.

Plain language summary

Funding research projects and activities to advance research towards treatments for dentatorubral-pallidoluysian atrophy (DRPLA) This article describes the journey of CureDRPLA, a family-driven non-profit organization dedicated to making strides against dentatorubral-pallidoluysian atrophy (DRPLA), an ultra-rare brain disorder. It describes CureDRPLA’s tireless efforts to understand, treat, and raise awareness about DRPLA, a condition marked by movement difficulties (ataxia), intellectual disability, uncontrollable jerky movements (myoclonus), involuntary or irregular muscle movements (chorea) and seizures. This disorder is caused by a mutation in a gene called ATN1. The gene produces a protein called atrophin-1, and when the DRPLA-causing mutation is present, the protein becomes abnormal and can build up in the brain, affecting its normal functions. Since its founding in 2019, CureDRPLA has funded research projects to unravel the mysteries of the disease and provide support for affected individuals. CureDRPLA has funded projects to create models of DRPLA using human cells and mice, which helps scientists study the disease and test potential treatments. We have started a study to learn more about how DRPLA progresses in people and are building a global database of information from individuals with DRPLA. Due to the absence of a treatment or cure, CureDRPLA is focused on testing treatments. We are particularly interested in exploring different approaches to lower the levels of the abnormal protein in the brain. CureDRPLA is actively involving the DRPLA community worldwide, raising awareness through events, conferences, and social media. We aim to connect with medical professionals, researchers, and affected families to build a strong community focused on understanding and managing DRPLA. In summary, CureDRPLA is working hard to better understand DRPLA, support affected families, and accelerate the development of treatments for this challenging condition. Our collaborative efforts and dedication underscore the importance of a united global approach to address the complexities of DRPLA.

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Conflict of interest statement

SP declares no competing interests. JBC is a paid advisor for Cajal Neuroscience and Guidepoint. He has received research support from Ionis Pharmaceuticals and Wave Life Sciences.

Figures

Figure 1.
Figure 1.
Overview of the efforts led by CureDRPLA to advance research toward treatments. CureDRPLA, in partnership with Ataxia UK, plays a pivotal role in propelling research efforts for DRPLA. The organization allocates funds to both academic institutions and commercial partners, supporting the development of essential tools for research, such as cell and animal models. This funding facilitates a deeper understanding of the function of the ATN1 gene and the underlying pathophysiological mechanisms in DRPLA. These collaborative projects contribute significantly to the progress of drug discovery, preclinical studies, and clinical research. To prepare for future clinical trials, CureDRPLA actively manages a patient registry and funds a natural history and biomarkers study. By doing so, the organization aims to gather crucial information that will inform future trial designs. Furthermore, the organization has dedicated some funds to document the lived experiences of individuals affected by DRPLA and their caregivers, as well as elevating awareness about DRPLA, advocating for improved care, and advancing therapies toward clinical application. Image created with BioRender.com. DRPLA, dentatorubral-pallidoluysian atrophy.
See this image and copyright information in PMC

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