Lamivudine in Individuals With Rett Syndrome: Clinical, Biochemical, and Cellular Evaluation
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 10
- 试验地点
- 1
研究概览
简要总结
Rett syndrome (RTT) is a rare genetic neurodevelopmental disorder caused primarily by mutations in the MECP2 gene, leading to progressive impairments in motor function, communication, and behavior following an initial period of apparently typical development. Currently, there are no treatments that change the course of the disease, and clinical care is largely focused on managing symptoms. Loss of MeCP2 function has been associated with increased activity of the LINE-1 (L1) retroelement, which may contribute to neuroinflammation and cellular stress in the brain. Lamivudine, a nucleoside reverse transcriptase inhibitor widely used in antiviral therapy, can inhibit L1 reverse transcription and has shown beneficial effects in preclinical models of RTT, including reductions in inflammatory and oxidative stress markers and improvements in neurological and behavioral outcomes. This study aims to evaluate the safety and potential clinical and biological effects of lamivudine in individuals with Rett syndrome using a before-and-after treatment design. Participants will receive oral lamivudine and will undergo clinical assessments and laboratory testing before and after the treatment period to evaluate changes in symptom severity, functional status, quality of life, seizure activity, and biomarkers related to inflammation and neurodevelopment. Biological samples will also be collected to support translational laboratory studies aimed at improving understanding of disease mechanisms and treatment response in RTT. Results from this study may help determine whether lamivudine is a safe and promising therapeutic option and may guide future clinical research in this population.
详细描述
Rett syndrome (RTT) is a rare genetic neurodevelopmental disorder caused primarily by loss-of-function mutations in the MECP2 gene, leading to progressive impairments in motor, cognitive, and communicative function after an initial period of apparently typical development. Currently, there are no medications that change the course of the disease, and treatment is mainly focused on managing symptoms.
Functional MeCP2 represses the activity of the LINE-1 (L1) retroelement, and loss of this repression may result in increased L1 accumulation in glial cells in the brain, promoting genomic instability, oxidative stress, and neuroinflammation associated with RTT pathophysiology.
Lamivudine inhibits L1 reverse transcription and has shown beneficial effects in preclinical neuronal culture and MeCP2-deficient mouse models, including reduced inflammatory and oxidative stress markers, improved neurological and behavioral outcomes, and increased survival. In this study, each participant is evaluated before and after receiving treatment, allowing changes to be assessed within the same individual over time. Following screening and baseline assessments, participants enter a treatment phase during which oral lamivudine is administered for a defined period. Longitudinal clinical, laboratory, and safety evaluations are conducted at scheduled visits, followed by a post-treatment follow-up period to assess the persistence of effects.
A 24-week intervention period was selected as a feasible and acceptable duration for participants and caregivers and as an appropriate timeframe for an initial open-label evaluation of therapeutic potential. This duration is expected to provide sufficient exposure to lamivudine to allow detection of short-term clinical and biological changes suggested by preclinical studies, while also enabling systematic assessment of safety and tolerability in this population.
Participants may continue their usual medical treatments, including medications for seizures and other supportive therapies, as long as these treatments remain stable during the study, unless a change is medically necessary.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Clinical and molecular diagnosis of Rett syndrome;
- •Age 2 years or older at the time of enrollment;
- •Ability to swallow liquid medication;
- •Stable clinical condition, as determined by the study investigator;
- •Availability of a parent or legal guardian able to provide informed consent and comply with study procedures;
- •Willingness of the participant and/or legal guardian to comply with study visits and assessments.
排除标准
- •Known hypersensitivity or contraindication to lamivudine;
- •Severe hepatic or renal impairment that, in the investigator's judgment, would preclude safe participation;
- •Use of investigational drugs or participation in another clinical trial within a defined washout period before enrollment;
- •Presence of any medical condition or acute illness that could interfere with study participation or outcome assessment, as determined by the investigator;
- •Inability to undergo blood collection or skin biopsy procedures required for the study;
- •Any condition that, in the opinion of the investigator, would place the participant at undue risk or compromise adherence to the study protocol.
研究者
Maria Denise Fernandes Carvalho de Andrade
Principal Investigator, Geneticist, and Physician
Universidade Estadual do Ceara