2002 results about "Mitochondrion" patented technology

Mitochondrial targets for drug screening assays and for therapeutic intervention in the treatment of diseases associated with altered mitochondrial function are provided. Complete amino acid sequences [SEQ ID NOS:1-3025] of polypeptides that comprise the human heart mitochondrial proteome are provided, using fractionated proteins derived from highly purified mitochondrial preparations, to identify previously unrecognized mitochondrial molecular components.

The identification of mutations that are present in a small fraction of DNA templates is essential for progress in several areas of biomedical research. Though massively parallel sequencing instruments are in principle well-suited to this task, the error rates in such instruments are generally too high to allow confident identification of rare variants. We here describe an approach that can substantially increase the sensitivity of massively parallel sequencing instruments for this purpose. One example of this approach, called “Safe-SeqS” for (Safe-Sequencing System) includes (i) assignment of a unique identifier (UID) to each template molecule; (ii) amplification of each uniquely tagged template molecule to create UID-families; and (iii) redundant sequencing of the amplification products. PCR fragments with the same UID are truly mutant (“super-mutants”) if ≧95% of them contain the identical mutation. We illustrate the utility of this approach for determining the fidelity of a polymerase, the accuracy of oligonucleotides synthesized in vitro, and the prevalence of mutations in the nuclear and mitochondrial genomes of normal cells.

The invention provides a method and a device for detecting mutated proteins. The method includes acquiring transcriptome data corresponding to samples; comparing the transcriptome data to mitochondrion databases and outputting non-mitochondrion sequences according to comparison results of the transcriptome data and the mitochondrion databases; transforming nucleotide sequences in the non-mitochondrion sequences into amino acid sequences, comparing the transformed amino acid sequences to protein databases and extracting amino acid sequences with homogenous rates in first set ranges and amino acid lengths in second set ranges from comparison results of the transformed amino acid sequences and the protein databases; comparing the extracted amino acid sequences with the homogenous rates in the first set ranges and the amino acid lengths in the second set ranges to NCBI (national center of biotechnology information) and determining the mutated proteins according to comparison results of the extracted amino acid sequences and the NCBI. According to the scheme, the method and the device have the advantage that the mutated proteins in the samples can be detected by the aid of the method and the device.

We describe a method for interrogating the content and primary structure of DNA by microarray analyses and to provide comprehensive genetic screening and diagnostics prior to embryo transfer within an IVF setting. We will accomplish this by the following claims: 1) an optimized embryo grading system, 2) a less invasive embryo biopsy with reduced cellular contamination, 3) an optimized DNA amplification protocol for single cells, 4) identify aneuploidy and structural chromosome abnormalities using microarrays, 5) identifying sub-telomeric chromosome rearrangements, 6) a modified DNA fingerprinting protocol, 7) determine imprinting and epigenetic changes in developing embryos, 8) performing genome-wide scans to clarify / diagnose multi-factorial genetic disease and to determine genotype / haplotype patterns that may predict future disease, 9) determining single gene disorders with or without a known DNA mutation, 10) determining mtDNA mutations and / or the combination of mtDNA and genomic (nuclear) DNA aberrations that cause genetic disease.

Systems, devices, and methods for releasing one or more cell components from a photosynthetic organism. A bioreactor system is operable for growing photosynthetic organisms. Some of the methods include contacting the photosynthetic organism with an energy-activatable sensitizer, and activating the energy-activatable sensitizer, thereby releasing a cellular component from at least one of, for example, a membrane structure, tubule, vesicle, cisterna, organelle, cell compartment, plastid, or mitochondrion, associated with the photosynthetic organisms.

The invention relates the method of treatment or amelioration of mitochondrial disorders such as Alzheimer's disease, Parkinson's disease, Friedreich's ataxia (FRDA), cerebellar ataxias, Leber's hereditary optic neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), Myoclonic Epilepsy with Ragged Red Fibers (MERFF), amyotrophic lateral sclerosis (ALS), motor neuron diseases, Huntington's disease, macular degeneration, and epilepsy, with chroman derivatives of Formula I or Formula II as described herein.

Disclosed herein are compositions to meet the needs of individuals, including humans and pets. Nutritional beverages, powders to make the same, a pudding and a nutritional bar are disclosed whose compositions include the R-alpha-lipoic acid in the amount of 0.12 grams to 1.5 grams and L-carnitine in the amount of 0.12 grams to 3 grams in addition to the usual composition. Optionally, effective amounts of coenzyme Q and / or creatine also are added. These additional components fight age-related declines in mitochondrial function which result in less energy and other signs of aging.

A topical skin rejuvenation preparation to relieve wrinkles, increase the skin's natural production of hyaluronic acid, reverse the lack of suppleness, hydrate from within, erase spider veins, reduce varicose veins, lighten aging dark blotches (“liver spots” / Lentigos, Senile Lentigines), decrease acne, and reduce under eye puffiness includes Glucosamine (2-amino-2-deoxy-alpha-D-glucose), a hexosamine (6 carbon amino sugar), including its derivative and precursor compounds: Glucosamine Sulfate, Glucosamine Hydrochloride, Glucose-6-Phosphate, Acetyl Glucosamine, Fructose-6-phosphate, Glucosamine-6-Phosphate, to increase production of Hyaluronic acid and collagen from Glucosamine Sulfate, its precursors and derivatives and to increase skin muscle tone by Dimethylaminoethanol (DMAE) while over coming deficiency it creates in each cell's production of PhosphatidylCholine, whose deficiency damages cell membranes, as well as mitochondrial and lysosome membranes.

Methods and compositions comprising peroxisomal and / or mitochondrial beta oxidation stimulating agents to reverse or resolve, slow the progression of, treat or prevent the development of fatty liver and conditions stemming from fatty liver, such as NASH, liver inflammation, cirrhosis and liver failure. An active agent that by itself is associated with an increased risk of fatty liver development and conditions stemming from fatty liver, such as NASH, liver inflammation, cirrhosis and liver failure, may be administered in combination with peroxisomal and / or mitochondrial beta oxidation stimulating agents. A combination regimen involving such agents, as simultaneous or concomitant therapy, or as a fixed dosage form, is also provided.

The present invention relates to the use of individual fumaric acid derivatives or mixtures thereof for preparing a pharmaceutical composition for treating mitochondrial diseases, especially for treating Parkinson's syndrome, Alzheimer's disease, Chorea Huntington disease, retinopathia pigmentosa and mitochondrial encephalomyopathy. Preferably, the fumaric acid derivative(s) is / are those selected from the group consisting of fumaric acid dialkyl esters or fumaric acid monoalkyl esters in the form of the free acid or a salt thereof.

Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), or Kearns-Sayre Syndrome (KSS) are disclosed, as well as compounds useful in the methods of the invention. Methods and compounds useful in treating other disorders are also disclosed. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed.

The present invention provides methods for rapid forensic analysis of mitochondrial DNA by amplification of a segment of mitochondrial DNA containing restriction sites, digesting the mitochondrial DNA segments with restriction enzymes, determining the molecular masses of the restriction fragments and comparing the molecular masses with the molecular masses of theoretical restriction digests of known mitochondrial DNA sequences stored in a database.

Provided herein are methods of culturing cells in vitro in order to exploit the biochemical production ability of the cells to make metabolites that are evaluated and harvested for their biological effects. Also provided are systems for evaluating extracts from such cultured cells to characterize their biological activity(s), particularly with regard to impact on health, wellbeing, longevity, DNA maintenance, mitochondrial health and / or biogenesis, and so forth. Biologically active extracts, components thereof, and compositions (such as cosmetic or pharmaceutical preparations) made comprising such, are also provided.

The present invention relates to chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides compounds as therapeutic agents to treat a number of conditions associated with the faulty regulation of the processes of programmed cell death, autoimmunity, inflammation, hyperproliferation, mitochondrial F1F0 ATP hydrolase associated disorders, and the like.

The invention provides a method of reducing or preventing mitochondrial permeability transitioning. The method comprises administering an effective amount of an aromatic-cationic peptide having at least one net positive charge; a minimum of four amino acids; a maximum of about twenty amino acids; a relationship between the minimum number of net positive charges (pm) and the total number of amino acid residues (r) wherein 3pm is the largest number that is less than or equal to r+1; and a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (pt) wherein 2a is the largest number that is less than or equal to pt+1, except that when a is 1, pt may also be 1.

The present invention provides methods for rapid forensic analysis of mitochondrial DNA and methods for characterizing heteroplasmy of mitochondrial DNA, which can be used to assess the progression of mitochondrial diseases.

Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), Kearns-Sayre Syndrome (KSS), are disclosed, as well as compounds useful in the methods of the invention, such as 2-(3-hydroxy-3-methyl-butyl)-6-(het)aryl-p-quinone or as 2-(3-hydroxy-3-methylbutyl)-3-(het)aryl-p-quinone derivatives. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed.

The present invention relates to the use of creatine compound and neuroprotective combinations including creatine, creatine phosphate or analogs of creatine, such as cyclocreatine, for treating diseases of the nervous system. Creatine compounds in combination with neuroprotective agents can be used as therapeutically effective compositions against a variety of diseases of the nervous system such as diabetic and toxic neuropathies, peripheral nervous system diseases, Alzheimer disease, Parkinson's disease, stroke, Huntington's disease, amyotropic lateral sclerosis, motor neuron disease, traumatic nerve injury, multiple sclerosis, dysmyelination and demyelination disorders, and mitochondrial diseases. The creatine compounds which can be used in the present method include (1) creatine, creatine phosphate and analogs of these compounds which can act as substrates or substrate analogs for creatine kinase; (2) bisubstrate inhibitors of creatine kinase comprising covalently linked structural analogs of adenosine triphosphate (ATP) and creatine; (3) creatine analogs which can act as reversible or irreversible inhibitors of creatine kinase; and (4) N-phosphorocreatine analogs bearing non-transferable moieties which mimic the N-phosphoryl group.

The present invention discloses novel mechanisms in the aging process and describes novel methods for high-throughput screening to identify, detect, and purify agents to be used for improving mitochondrial function, maintaining the cell cycle-arrested state in senescent and post mitotic cells, and thus preventing or treating age-related diseases or disorders associated with accelerated mitochondrial function loss, telomere dysfunction, and / or deterioration of the growth-arrested state. The present invention also discloses a number of compounds or compositions identified from this method. The present invention further provides the use of low doses of rapamycin or its analogs as a mimic of caloric restriction in preventing age-related diseases or disorders.

A method of detecting presence or absence of prostate cancer in a subject, both in vivo and ex vivo is disclosed. The method comprises analyzing mitochondria or a mitochondrial component in at least one prostate cell of the subject, whereby mitochondria an alteration in quantity and or characteristic is indicative of the presence or absence of the prostate cancer in the subject.

Methods of treating, preventing or suppressing symptoms associated with mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), dominant optic atrophy (DOA); mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), Leigh syndrome or Kearns-Sayre Syndrome (KSS) with compounds of Formula (I) are disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods are also disclosed.

Methods for the reduction of mitochondrial oxidative damage and improved mitochondrial efficiency in an animal by administration of medium chain triglycerides or prodrug of medium chain triglycerides to the animal are provided.

Provided are compositions comprising compounds or precursors to compounds which may be used for a variety of therapeutic applications including, for example, treating and / or preventing a disease or disorder related to reduced or inadequate mitochondrial activity, including aging or stress, diabetes, obesity, and neurodegenerative diseases. The compounds relate generally to urolithins and precursors thereof, including but not limited to ellagitannins and urolithin A. In certain embodiments the compositions are presented in or as food products or nutritional supplements. These same compounds and compositions can also be used advantageously in generally healthy individuals to increase or maintain metabolic rate, decrease percent body fat, increase or maintain muscle mass, manage body weight, improve or maintain mental performance (including memory), improve or maintain muscle performance, improve or maintain mood, and manage stress.

Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS), Kearns-Sayre Syndrome (KSS), are disclosed, as well as compounds useful in the methods of the invention, such as 4-(p-quinolyl)-2-hydroxybutanamide derivatives. Methods and compounds useful in treating other disorders such as amyotrophic lateral sclerosis (ALS), Huntington's disease, Parkinson's disease, and pervasive developmental disorders such as autism are also disclosed. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed.

A method for preventing, reducing, ameliorating or treating ophthalmic disorders associated with neurodegenerative diseases or trauma, comprising the topical, periocular, or intraocular application of an ophthalmic formulation comprising a therapeutically effective amount of one or more ophthalmic agents selected from the group consisting of alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, delta-tocotrienol, or esters or mixtures thereof is disclosed. Use of tocotrienols for the prevention, reduction, amelioration or treatment of ophthalmic disorders that are, or that are associated with, mitochondrial diseases is also discussed. Topical ophthalmic formulations comprising tocotrienols are also discussed.

The present invention provides methods and compositions related to the fields of chemoinformatics, chemogenomics, drug discovery and development, and drug targeting. In particular, the present invention provides subcellular localization signals (e.g., chemical address tags) that influence (e.g., direct) subcellular and organelle level localization of associated compounds (e.g., drugs and small molecule therapeutics, radioactive species, dyes and imagining agents, proapoptotic agents, antibiotics, etc) in target cells and tissues. The compositions of the present invention modulate the pharmacological profiles of associated compounds by influencing the compound's accumulation, or exclusion, from subcellular loci such as mitochondria, endoplasmic reticulum, cytoplasm, vesicles, granules, nuclei and nucleoli and other subcellular organelles and compartments. The present invention also provides methods for identifying chemical address tags, predicting their targeting characteristics, and for rational designing chemical libraries comprising chemical address tags.

The invention provides a method of reducing or preventing mitochondrial permeability transitioning. The method comprises administering an effective amount of an aromatic-cationic peptide having at least one net positive charge; a minimum of four amino acids; a maximum of about twenty amino acids; a relationship between the minimum number of net positive charges (pm) and the total number of amino acid residues (r) wherein 3pm is the largest number that is less than or equal to r+1; and a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (pt) wherein 2 a is the largest number that is less than or equal to pt+1, except that when a is 1, pt may also be 1.

Methods of treating, preventing or suppressing symptoms associated with mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), dominant optic atrophy (DOA); mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), Leigh syndrome or Kearns-Sayre Syndrome (KSS) with vitamin K are disclosed.

The invention relates to a biological detection reagent capable of discriminating three types of ruminant animal varieties simultaneously, a preparation method and an application thereof. The invention selects the specificity of the cow, goat and sheep, and the conservative sequence segment of conservative mitochondrial gene as target, applies Primer Eexpress 3.0 software and Primer Select software in DNAStar, and designs and synthesizes a plurality of groups of primers and probes. After being synthesized and marked, the plurality of pairs of designed primers and the probes are carried out best pairing screening experiment so as to obtain the fittest combination of primers and probes. The reagent contains two pairs of specificity primers, and three Taq Man probes, wherein one pair of theprimer aims at cow source components, the other pair of primer aims at common primers of goats and sheep source component detection; the three probes are respective source components to the cows, thegoats and the sheep; and the amplified target fragment length to the source component detection of the cows, the goats and the sheep is respectively 92bp, 136bp and 136bp. The triple Taq Man fluorescence PCR detection method can simultaneously carry out accurate quantitative detection to the source components of the cows, the goats and the sheep, has simple and convenient operation, intuitive result, strong specificity, high sensitivity and good repeatability and can realize high throughput detection of various source components.

A method for treating obesity by activating non-shivering thermogenesis in mitochondria of targeted brown adipose tissue. A photobiomodulation device including one or more light sources is provided. The mitochondria of the targeted brown adipose tissue is photobiomodulated by exposure to light produced by the light source at a wavelength that modulates photoactivity of an electron transport chain and increases proton transfer across a membrane of the mitochondria of the targeted brown adipose tissue towards an intern space of the mitochondria, without increasing production of adenosine triphosphate.