Active clinical trials for "Mitochondrial Myopathies"

Rationale: Mitochondrial disorders are progressive, often fatal multisystem disorders, in 20-25% of the cases caused by heteroplasmic mutations in the mitochondrial DNA (mtDNA). At this moment, there is no effective treatment known to influence the disease process or manifestation. Myogenic stem cell-based therapies complementing defective muscle cells and fibres, are highly promising to combat the myopathy and exercise intolerance which affect >50% of heteroplasmic mtDNA mutation carriers. Myogenic stem cells called mesoangioblasts (MABs), are currently the only myogenic precursors that fulfil all criteria to be used as advanced therapy medicinal product (ATMP) for systemic treatment. The researchers have demonstrated that MABs of most m.3243A>G carriers contain no or only a low amount (<10%) of the mtDNA mutation, allowing direct ex vivo expansion of patient-derived MABs. The overall aim is to induce muscle regeneration using these autologous MABs with a mutation load of <10%, as an advanced therapy medicinal product (ATMP). Objective: The phase I trial will consist of an intra-arterial injection (via catheter in femoral artery) of the autologous MABs in the left lower leg of 5 m.3243A>G patients.

The purpose of the phase 2 portion of this study is to select a biologically-active ASP0367 dose level by pharmacokinetic (PK) and pharmacodynamic (PD) evaluation. The phase 2 portion of this study will also assess the safety and tolerability of ASP0367. The purpose of the phase 3 portion of this study is to assess the effect of ASP0367 on functional improvement relative to placebo and will also assess the safety and tolerability of ASP0367 relative to placebo. The phase 3 portion of this study will also assess the effect of ASP0367 on functional improvement and fatigue relative to placebo and will assess the effect of ASP0367 in overall participant functioning relative to placebo.

The purpose of this study is to determine the effects of Nicotinamide Riboside (NR) supplement in adult-onset symptoms of mitochondrial myopathy.

The first primary objective is to assess the effect of three intra-arterial administrations of autologous mesoangioblasts (MABs) with respect to improving muscle strength and reduce fatigue of the treated biceps brachii (BB) compared to the untreated BB. The second primary objective is safety of three intra-arterial administrations of autologous MABs, which the investigators will assess by monitoring (serious) adverse events ((S)AEs), blood flow in left arm pre- and post-intervention, and neurological vital signs during 8h post-intervention observation in the hospital. Secondary objectives are to assess changes in muscle mass of the treated and untreated BB muscle, and microscopic changes and m.3243A>G mutation load at tissue level in treated biceps brachii (BB) muscle at baseline and after treatment. Up to 20 adult m.3243A>G patients will undergo a ~30mg m. biceps brachii muscle biopsy at visit 1. The first six eligible patients will enroll the clinical study based on their m.3243A>G mutation load in skeletal muscle (50-90%) and mesoangioblasts (<10%), and on a decreased BB muscle strength and increased fatigue. These 6 selected patients will visit the Maastricht University Medical Center for 8 additional times. From each patient, during visit 2 till 9: BB muscle biopsies of the left arm will be collected (1x ~130 mg at visit 2 and 1x ~30mg at visit 9) MRI of the BB muscles in both arms will be performed (visit 2 and 9). Autologous MABs will be injected into the left arm via axillary artery delivery. Angiography will be performed before and after infusion to assess vascular obstructions, and the participant will be monitored in the hospital for 8 hours (visit 4,6,8). Tc99m macroaggregated albumin (MAA) is infused to quantify blood flow to the BB muscle (visit 4). A bout of maximal eccentric exercise of BB muscles on both sides will be executed at visit 3, 5 and 7. BB muscle strength will be assessed using a Biodex dynamometer (visit 3-9) venous blood samples will be taken for assessing muscle damage and inflammation markers (visit 3-9), kidney functioning, coagulation and viral screening (visit 1 and 2).

The goal of this study is to find the best way to help people with primary mitochondrial disease deal with the stress of their condition, and to help these people be better able to "bounce back," or be resilient. In order to do this, the investigators are going to test two interventions (an intervention means that it aims to change something): Promoting Resilience in Stress Management (PRISM) and clinical-focused narrative (CFN) intervention.

Positive effect of physical activity on health arouses a strong interest at international level and is developped within the scope of national programs. Recommandations exist but must be designed for patients with functional limitations of activities. Patients with mitochondrial diseases have exercice intolerance with an increase of muscular weakness and fatigue after low exercice volume. Theses patients have functional limitations of activities. In order to establish an appropriate training programme, it will be important to define and consider the physical condition. The Society of Mitochondrial Medecine published recommandations for management of theses patients,However, theses recommandations do not allow them to propose a training program of what can be done. For these vulnerable patients, therapists are responsible fo advising a training programm without guidelines to establish its terms and conditions. In addition, some exercices do not appear to have been the subject of complete assessmeents. Regarding training programs (aerobic training, muscle reinforcement, miwed training), scientific literature shows a significant genetic and clinical variabilities, as well as a lack of data on clinical severity of included patients. In addition, the lack of informations regarding training effects of heteroplamy level limits our comprehension of mechanisms involved in adaptation of mitochondrial pool during training. Therefore, further reserchs on this subject are essential. It is necessary to offer these patients a follow-up and personalized training program, which are in adequation with daily life. Some publications call on specifics concepts which are not compatible with day-to-day life. The investigators think it will be useful to investigate training effects in order to have practival conclusions, easily reproducible at home by patients with simple and inexpensive equipment. In this context, video consultation could allow the close follow-up of these patients. The investigators hypothesize that a mixed training (endurance and muscle reinforcement), personalized, at home and followed by video consultation have positive effects on some physical criteria (such as musclar strength, tolerance to effort, functional abilities) without increasing heteroplasmy and creatine phosphokinase levels.

This is a multi-aim study, studying the effects of conventional exercise (measured through Cardiopulomary Exercises Testing or an in-bed pedal exercise) and passive exercise through periodic acceleration (pGz). Aim 1 will focus on the differences between primary mitochondrial disease (PMD) patients and healthy volunteers. Aim 2 is an exploratory aim, which will be studying the effects in patients admitted to the Children's Hospital of Philadelphia Pediatric Intensive Care Unit (PICU).

This study is designed to evaluate the long-term safety and tolerability of REN001 administered once daily to subjects with PMM due to mitochondrial DNA mutations (mtDNA-PMM) or nuclear DNA mutations (nDNA-PMM). Subjects with mtDNA mutations will have previously completed Study REN001-201 or participated in Study REN001-101. Subjects with nDNA mutations who enroll in this study will be REN001- naïve.

Past mitochondrial disease treatment studies have been unsuccessful in determining treatment efficacy, and a major factor has been the lack of validated biomarkers in mitochondrial myopathy (MM). There is currently a growing number of potential new treatments to be tested through MM clinical intervention trials, which has created a pressing need for quantitative biomarkers that reliably reflect MM disease severity, progression, and therapeutic response. The purpose of the study is to measure the efficacy of an electrochemical oxygen nanosensor to measure in vivo mitochondrial function in human muscle tissue, and its ability to discriminate MM patients from healthy volunteers. The data and results from this nanosensor study may contribute to current and future research, including improved diagnostic and therapeutic approaches for patients with mitochondrial disease.

The aims of the current study are as follow: i) Evaluate the safety, usability, and acute efficiency of a powered knee-hip dermoskeleton (MyoSuit, MyoSwiss, Zurich, Switzerland) in patients with neuromuscular disorders, ii) Elaborate recommendations regarding usability criteria for safe and efficient use the device in patients with neuromuscular disorders (e.g. type and severity of patient's functional deficits), iii) generate necessary data to foresee a future study involving a home use of the device and assessment of long-term benefits.