Active clinical trials for "Mitochondrial Diseases"

The aim of this study is to assess nutritional intake (quantitatively and qualitatively), nutritional state and body composition of patients suffering from mitochondrial cytopathy, compared to healthy controls. The energy intake will be calculated through dietary protocols, the energy expenditure by indirect calorimetry and body composition will be performed with bio-impedance analysis. Further on, the investigators expect to be able to provide nutritional counselling to this population in order to increase energy and protein intake, which may improve health and well-being.

A previous NAMDC survey study (NAMDC 7414 - Diagnostic Odyssey Survey, referred to hereafter as Odyssey1), provided a benchmark account of the substantial challenges faced by patients in achieving a diagnosis of mitochondrial disease, and of the impact such a diagnosis has on them (Grier et al. 2018).1 This study was conducted from October 2015 through January 2016. We propose a new survey study (Odyssey2) which will provide an update, additional data collection (duration of the diagnostic odyssey), and allow assessment of next-generation DNA sequencing techniques since Odyssey1 concluded. Odyssey2 will retain the strengths (simplicity, brevity, confidentiality, and data quality assurance measures) which made Odyssey1 successful. While Odyssey2 adds some refinements based on experience learned from Odyssey1, the basic questions are changed as little as possible to maximize comparability, and the additions are limited. Odyssey1 consisted of between 16 and 23 questions, depending on skip patterns, and took an estimated 15 minutes to complete. Odyssey2 consists of between 23 and 33 questions, depending on skip patterns and we estimate that it will take approximately 20 minutes to complete. As in Odyssey1, only patients who report, directly or through a guardian, that they have been informed by a doctor that they have a confirmed mitochondrial disorder will be eligible for Odyssey2.

Numerous studies have demonstrated that excess perivisceral adipose tissue is associated with metabolic diseases such as insulin resistance. In skeletal muscle, insulin resistance has been correlated with reduced mitochondrial oxidative functions. According to the actual theory, mitochondrial dysfunctions are proposed to play a causal role in the aetiology of insulin resistance. Mechanisms involve increased intramyocellular lipids storage. Yet, the causes responsible for the decline in muscle mitochondrial functions remain to be elucidated. The investigators hypothesize that these alterations are induced by combined changes in plasma profiles of lipids and adipokines, which originate from perivisceral adipose tissue. The study aims at answering the following questions : Are muscle mitochondrial functions altered in association with increased perivisceral adipose tissue storage? Do changes in the pattern of plasma lipids and adipokines explain this correlation?

Older adults with human immunodeficiency virus (HIV) and a long history of antiretroviral therapy have more mitochondrial dysfunction- the cells that help them make energy. This dysfunction in mitochondria may lead to symptoms of muscle fatigue, physical function impairment, and impaired exercise tolerance compared to HIV-uninfected controls of a similar age and body mass index (BMI). Furthermore, the investigators hypothesize that the older antiretroviral therapy (ART) of tenofovir disoproxil fumarate (TDF) is associated with greater impairment in mitochondrial function than the newer agent, tenofovir alafenamide (TAF).

The purpose of this 3-year, multi-site, non-randomized, prospective, observational study is to characterize the natural history of Pearson Syndrome. The Syndrome is a rare mitochondrial disorder due to a large-scale mtDNA deletion. Children typically present in their 1st two years of life (most in infancy) with anemia and/or pancreatitis. Most individuals with Pearson Syndrome die in childhood. Those who survive evolve to Kearns-Sayre Syndrome/Chronic Progressive External Ophthalmoplegia (KSS/CPEO) although accurate survival estimates are not yet known.

Metabolic diseases and mitochondrial disorders are caused by genetic mutation which lead to disruptions in energy producing pathways in our body. Enough energy or calories must be given in the diet to ensure normal growth and development. Currently, energy needs for patients with metabolic and mitochondrial diseases are not measured, but is estimated using a mathematical equation based on healthy children. This may lead to under feeding or overfeeding of calories, and has negative nutritional implications. The clinical standard for measuring energy needs is the use of indirect calorimeter.The indirect calorimeter takes individualized measurements for each patient and therefore will enable dietitians and clinicians to provide sufficient calories in the diet to better manage the disease and promote normal growth and development. We believe daily energy requirements will vary within metabolic diseases (Phenylketonuria) and mitochondrial disorders (mitochondrial fatty acid oxidation defect, POLG1 mutation etc.). The objective of this preliminary study is to measure resting energy expenditure in children living with metabolic and mitochondrial conditions and data obtained will be used to generate future hypothesis and will form a basis for future studies.

Mitochondrial diseases are complex diseases with great clinical and genetic heterogeneity and their diagnosis is difficult. The Medical Genetics Department includes among its activities the diagnosis of these diseases. It has been a reference centre for mitochondrial diseases at the national level since 2006 and was recently approved under the call for projects "European Reference Network (ERN) for rare diseases", EURO-NMD, supported by the Nice University Hospital. The routine diagnostic strategy is based on high throughput mitochondrial DNA (mtDNA) sequencing analysis and a panel of 281 targeted "mitochondriopathies" genes. When these analyses are negative, an exome analysis (high throughput sequencing of all exons in the genome) can be performed in a research setting. To date, about 40% of the patients analysed remain without genetic diagnosis. Indeed, it does not allow to identify large variations of deletion, duplication or CNV (copy number variation) type. Moreover, targeting only exons, exome sequencing does not allow the detection of intronic or localized mutations in regulatory regions. The identification of CNVs is made possible by chromosomal analysis on a DNA chip (CADC). This recognized technique is used routinely in the laboratory. The investigators use chips with a minimum resolution of approximately 13Kb for the genome-wide study of CNVs in patients with developmental disorders. However, this resolution is insufficient to detect rework events of the order of magnitude of an exon. There are high-resolution DNA chips, compatible with our platform, that would allow the investigators to more accurately visualize smaller rearrangements that could not be identified by exome analysis. The combined exome/CADC strategy has already proven its effectiveness in diagnosing various diseases by increasing yield. In this context, the investigators aim to use this strategy in this non-interventional study on a series of 15 patients with mitochondrial disease who remain undiagnosed after analysis of mtDNA, gene panel and exome. They will test 2 types of patients: In the first series, whose disease is supposed to be transmitted in an autosomal recessive mode, only one heterozygous variant was identified in a gene already described in a comparable clinical picture. It is therefore possible that these patients are carriers on the second allele of a CNV, which the exome sequencing could not identify. In the second series, the exome analysis did not allow the identification of a single responsible gene (several candidate genes without any certainty on the pathogenicity of the gene(s) or variant(s))

2622/5000 Mitochondrial diseases (MM) are the most common metabolic diseases. Since these pathologies are very heterogeneous in clinical terms, only the identification of mutations in nuclear genes or mitochondrial DNA confirms the diagnosis. The full-scale study of mtDNA by high-throughput sequencing (NGS) is a first step in the diagnostic approach. The recent introduction of this revolutionary new technology has greatly increased the efficiency of mutation identification. However, in addition to known pathogenic mutations, NGS reveals numerous variants whose significance is currently unknown. A major challenge to obtain a reliable diagnosis is therefore the interpretation of the clinical impact of these new rare variants which proves to be very difficult. Pathogenicity criteria allow the classification of variants from benign to pathogenic. One of the major pathogenicity criteria is a good correlation of heteroplasmic level with tissue or cellular involvement. Indeed, mtDNA mutations are generally heteroplasmic, which corresponds to the coexistence of normal and mutated molecules in the same cell or tissue, the most affected tissues having a high rate of mutation. On a muscle biopsy of an affected patient, the fibers often present an enzyme deficiency in cytochrome c oxidase (COX-negative) which can be demonstrated in immunohistochemistry. The single fiber study allows to isolate the deficient fibers and to quantify the heteroplasmic rate of a variant. The presence of a high level of heteroplasm in the COX-negative fibers, unlike fibers without deficit, is a strong argument in favor of the pathogenicity of this variant. Currently, this technique is not used routinely in diagnostic laboratories but only occasionally in a research framework in some laboratories. It is a heavy technique that consists of a first stage of laser microdissection of the various muscle fibers followed by a second step of quantification of the variant from each fiber. This second step requires a specific focus for each identified variant. The aim of this pilot study is to develop a new technique for quantification of single-fiber heteroplasmics isolated by NGS laser microdissection. This, independent of the type of variant, will avoid the long and costly adjustments required for each new variant identified and thus facilitate its use

Choosing to participate in an expanded access program is an important personal decision. Talk with your doctor to learn more about this program. The treating physician must contact StealthBiotherapeutics using the Expanded Access Program Contacts provided. Elamipretide will only be made available after careful review of an individual request submitted by the treating physician. The initiation and conduct of the treatment with elamipretide for an individual patient, and compliance with this treatment guideline, will be under the full and sole responsibility of the treating physician.

This study evaluates metabolic and functional parameters in the skeletal muscle of Parkinson's disease patients for comparison to a set of healthy age-matched controls.