Merav Darash-Yahanaa, Yair Pozniakb, Mingyang Luc, Yang-Sung Sohn, Ola Karmi, Sagi Tamir, Fang Bai, Luhua Song, Patricia A. Jennings, Eli Pikarsky, Tamar Geiger, José N. Onuchic, Ron Mittler and Rachel Nechushtai, PNAS early/2016/09/07, DOI:10.1073/pnas.1612736113
Freely available online through the PNAS open access option.
Disrupted expression of frataxin, another protein involved in Fe-S biogenesis, in hepatocytes of transgenic mice similarly led to impaired mitochondrial function, oxidative stress, and the development of multiple hepatic tumors. Moreover, ISCU and frataxin are regulated at the transcriptional level by p53 controlling the levels of ROS in cells
Sunday, September 18, 2016
Saturday, September 17, 2016
Retrotope Announces Phase I/II Clinical Trial Results of RT001 in Treatment of Friedreich's Ataxia
LOS ALTOS, CA--(Marketwired - Sep 16, 2016) - Dr. Theresa Zesiewicz, principal investigator in Retrotope's first-in-human clinical trial of RT001 in Friedreich's ataxia (FA), today presented early results from Retrotope's Phase I/II trial conducted at the University of South Florida Ataxia Research Center and the Collaborative NeuroSciences Network in Long Beach, CA. The trial, a randomized, double-blind, comparator controlled, two-dose study of RT001 in 18 FA patients for 28 days, met all of its primary safety, tolerability and pharmacokinetic (PK) goals. While biological activity was not a primary goal of the study, a number of clinically important activity measures were tested, found to be highly correlated to well-studied disease severity scales and showed multiple, unexpected, robust signals of drug effect at one or more doses.
Thursday, September 15, 2016
Characterization of human mitochondrial ferritin promoter: identification of transcription factors and evidences of epigenetic control
Michela Guaraldo, Paolo Santambrogio, Elisabetta Rovelli, Augusta Di Savino, Giuseppe Saglio, Davide Cittaro, Antonella Roetto & Sonia Levi; Scientific Reports 6, Article number: 33432 (2016) doi:10.1038/srep33432
The reagents Aza and NaB make the DNA accessible to transcription factors and activate FTMT expression. Our findings sustain that the moderate induction of FTMT expression by epigenetic therapy could be useful in disease characterized by oxidative stress, as FRDA.
The reagents Aza and NaB make the DNA accessible to transcription factors and activate FTMT expression. Our findings sustain that the moderate induction of FTMT expression by epigenetic therapy could be useful in disease characterized by oxidative stress, as FRDA.
Tuesday, September 13, 2016
UF and the Advocacy Group GoFAR Announce Gene Therapy program for Friedreich’s Ataxia
Press release: Gainesville - FL, Torino - IT, Sept.13, 2016
USF Health and FARA to host patient-focused scientific symposium Sept. 15
USF Health and FARA to host patient-focused scientific symposium Sept. 15 [Video], Written by Anne DeLotto Baier · September 12, 2016
International experts from academia and industry will gather to discuss advances in Friedreich’s ataxia from the laboratory to the clinic.
Tampa, FL (Sept. 12, 2016) — The University of South Florida (USF) will bring together leading researchers and patients searching for a treatment for Friedreich’s ataxia (FA) and related disorders at the eighth annual scientific symposium “Understanding Energy for A Cure.” The symposium will be held 5 to 8:30 p.m., Thursday, Sept. 15, at the USF Sam and Martha Gibbons Alumni Center, 11810 USF Alumni Drive, Tampa, FL 33620.
International experts from academia and industry will gather to discuss advances in Friedreich’s ataxia from the laboratory to the clinic.
Tampa, FL (Sept. 12, 2016) — The University of South Florida (USF) will bring together leading researchers and patients searching for a treatment for Friedreich’s ataxia (FA) and related disorders at the eighth annual scientific symposium “Understanding Energy for A Cure.” The symposium will be held 5 to 8:30 p.m., Thursday, Sept. 15, at the USF Sam and Martha Gibbons Alumni Center, 11810 USF Alumni Drive, Tampa, FL 33620.
Utility of Whole Exome Sequencing for Genetic Diagnosis of Previously Undiagnosed Pediatric Neurology Patients
Maya Kuperberg, Dorit Lev, Lubov Blumkin, Ayelet Zerem, Mira Ginsberg, Ilan Linder, Nirit Carmi, Sarah Kivity, Tally Lerman-Sagie, Esther Leshinsky-Silver; August 29, 2016, doi: 10.1177/0883073816664836
When a patient arrives with a suspected monogenic disease the authors first take detailed history, perform a full clinical exam, and create a family tree. If a specific genetic disease is suspected based on this data, direct traditional tests are to be performed. Only if the patient remains undiagnosed should the authors turn to whole exome sequencing. The authors were able to diagnose patients exhibiting nonspecific, atypical, or overlapping symptoms.
Over 300 genetic conditions are known to cause ataxia, and without additional specific symptoms achieving a diagnosis is very difficult. Whole exome sequencing studies on cerebellar ataxia have achieved a success rate of 18%-64%. The authors report a high success rate of 57.1% for patients with ataxia.
When a patient arrives with a suspected monogenic disease the authors first take detailed history, perform a full clinical exam, and create a family tree. If a specific genetic disease is suspected based on this data, direct traditional tests are to be performed. Only if the patient remains undiagnosed should the authors turn to whole exome sequencing. The authors were able to diagnose patients exhibiting nonspecific, atypical, or overlapping symptoms.
Over 300 genetic conditions are known to cause ataxia, and without additional specific symptoms achieving a diagnosis is very difficult. Whole exome sequencing studies on cerebellar ataxia have achieved a success rate of 18%-64%. The authors report a high success rate of 57.1% for patients with ataxia.
Saturday, September 10, 2016
The Application of Human Spinal Cord Magnetic Resonance Spectroscopy to Clinical Studies: A Review, Seminars in Ultrasound, CT and MRI
Patrik Oliver Wyss, Andreas Hock, Spyros Kollias, Available online 12 July 2016, ISSN 0887-2171, doi:10.1053/j.sult.2016.07.005.
Friedreich’s ataxia (FRDA) is an autosomal recessive degenerative disorder affecting the nervous system and the heart. Spectroscopic measurements in the brain showed decreased NAA in the vermis and the cerebellar hemispheres and increased myo-Inositol in the vermis. The total amount of Cr in the cerebellar hemispheres and Glu in the vermis was higher suggesting an alteration in the glutamatergic neurotransmission system. Findings in the spinal cord were in accordance with those of the brain showing a reduction of NAA by 40% and an increase of mI by 46% reflecting neuronal damage and gliosis.
Friedreich’s ataxia (FRDA) is an autosomal recessive degenerative disorder affecting the nervous system and the heart. Spectroscopic measurements in the brain showed decreased NAA in the vermis and the cerebellar hemispheres and increased myo-Inositol in the vermis. The total amount of Cr in the cerebellar hemispheres and Glu in the vermis was higher suggesting an alteration in the glutamatergic neurotransmission system. Findings in the spinal cord were in accordance with those of the brain showing a reduction of NAA by 40% and an increase of mI by 46% reflecting neuronal damage and gliosis.
Thursday, September 8, 2016
Introduction to Special Issue on Mitochondrial Redox Signaling in Health and Disease
Juan P. Bolaños, Enrique Cadenas, Michael R. Duchen, Mark B. Hampton, Giovanni E. Mann, Michael P. Murphy, Free Radical Biology and Medicine, Available online 5 August 2016, ISSN 0891-5849, doi:10.1016/j.freeradbiomed.2016.08.004.
The genetic deficiency of the mitochondrial protein frataxin is the cause of Friedreich ataxia. Frataxin deficiency is not associated with cognitive impairment, but with increased oxidative stress with alterations in lipid metabolism, which are discussed as potential therapeutic approaches in Friedreich ataxia. The mitochondrial Lon protease is involved in several neurological disorders, such as hereditary Parkinson’s disease, Friedreich ataxia, familial amyotrophic lateral sclerosis, brain ischemia and stroke. In these disorders, the physiological functions of the Lon protease are altered: as a protease, as a chaperone,and as a mtDNA binding protein.
The genetic deficiency of the mitochondrial protein frataxin is the cause of Friedreich ataxia. Frataxin deficiency is not associated with cognitive impairment, but with increased oxidative stress with alterations in lipid metabolism, which are discussed as potential therapeutic approaches in Friedreich ataxia. The mitochondrial Lon protease is involved in several neurological disorders, such as hereditary Parkinson’s disease, Friedreich ataxia, familial amyotrophic lateral sclerosis, brain ischemia and stroke. In these disorders, the physiological functions of the Lon protease are altered: as a protease, as a chaperone,and as a mtDNA binding protein.
Wednesday, September 7, 2016
Functional and Gait Assessment in Children and Adolescents Affected by Friedreich’s Ataxia: A One-Year Longitudinal Study
Gessica Vasco , Simone Gazzellini, Maurizio Petrarca, Maria Luisa Lispi, Alessandra Pisano, Marco Zazza, Gessica Della Bella, Enrico Castelli, Enrico Bertini, PLoS ONE 11(9): e0162463. doi:10.1371/journal.pone.0162463
Open access
Open access
Tuesday, September 6, 2016
Comparative Mitochondrial-Based Protective Effects of Resveratrol and Nicotinamide in Huntington’s Disease Models
Luana Naia, Tatiana R. Rosenstock, Ana M. Oliveira, Sofia I. Oliveira-Sousa, Gladys L. Caldeira, Catarina Carmo, Mário N. Laço, Michael R. Hayden, Catarina R. Oliveira, A. Cristina Rego; Mol Neurobiol (2016). doi:10.1007/s12035-016-0048-3
In this study, we tested the influence of resveratrol (RESV, a SIRT1 activator) versus nicotinamide (NAM, a SIRT1 inhibitor) in counteracting mitochondrial dysfunction in HD models. Further studies revealed decreased PGC-1α and TFAM protein levels, linked to mitochondrial DNA loss in HD lymphoblasts. Remarkably, RESV completely restored these parameters, while NAM increased NAD+ levels, providing a positive add on mitochondrial function in in vitro HD models. In general, RESV decreased while NAM increased H3 acetylation at lysine 9. In agreement with in vitro data, continuous RESV treatment for 28 days significantly improved motor coordination and learning and enhanced expression of mitochondrial-encoded electron transport chain genes in YAC128 mice. In contrast, high concentrations of NAM blocked mitochondrial-related transcription, worsening motor phenotype. Overall, data indicate that activation of deacetylase activity by RESV improved gene transcription associated to mitochondrial function in HD, which may partially control HD-related motor disturbances.
In this study, we tested the influence of resveratrol (RESV, a SIRT1 activator) versus nicotinamide (NAM, a SIRT1 inhibitor) in counteracting mitochondrial dysfunction in HD models. Further studies revealed decreased PGC-1α and TFAM protein levels, linked to mitochondrial DNA loss in HD lymphoblasts. Remarkably, RESV completely restored these parameters, while NAM increased NAD+ levels, providing a positive add on mitochondrial function in in vitro HD models. In general, RESV decreased while NAM increased H3 acetylation at lysine 9. In agreement with in vitro data, continuous RESV treatment for 28 days significantly improved motor coordination and learning and enhanced expression of mitochondrial-encoded electron transport chain genes in YAC128 mice. In contrast, high concentrations of NAM blocked mitochondrial-related transcription, worsening motor phenotype. Overall, data indicate that activation of deacetylase activity by RESV improved gene transcription associated to mitochondrial function in HD, which may partially control HD-related motor disturbances.
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