Identification of potential mitochondrial CLPXP protease interactors and substrates suggests its central role in energy metabolism

Fabian Fischer, Julian D. Langer & Heinz D. Osiewacz; (NATURE) Scientific Reports 5, Article number: 18375 (2015) doi:10.1038/srep18375

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Among the CLPP-associated pathologies is Friedreich’s Ataxia (FRDA), a neurodegenerative disease caused by failed assembly of Fe-S clusters due to defects in the mitochondrial iron chaperone frataxin31. In a FRDA mouse model, the proteolytic component CLPP is upregulated at mid-stage of the disease. This upregulation is concomitant with a loss of mitochondrial Fe-S proteins, indicating they are targets of CLPP in FRDA. Indeed, several proteins we identified in our study contain or bind to Fe-S clusters, e.g. aconitase, biotin synthase, and complex I components such as the NADH-ubiquinone oxidoreductase 75 kDa subunit. In addition, three of the proteins found as CLPXP interactors or substrates, the cysteine desulfurase NSF1, the chaperone HSPA9, and the glutaredoxin-related protein 5, are known to be essential for Fe-S cluster biogenesis in eukaryotic cells including those of mammals. Thus, our findings support the idea that CLPXP has a functional role in FRDA and might possibly be involved in regulating Fe-S cluster assembly and Fe-S cluster proteins.

The first therapeutics based on genome-editing tools will treat diseases caused by single genes, but many other factors dictate what is currently possible.

Virginia Gewin, Medicine: Expanding possibilities, Nature 528, S10–S11 (03 December 2015) doi:10.1038/528S10a Published online 02 December 2015

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Treatments for Syndromes of Progressive Ataxia and Weakness Disorders - PMR Market Insight Report to 2020

Persistence Market Research (PMR)

Stringent regulations and standard requires for approval process of new drugs impede growth of the treatments for syndromes of progressive ataxia and weakness disorders market. The approval process takes a very long time to approve a specific drug.

Burden of mitochondrial DNA variations in Friedreich's Ataxia (FRDA) patients and sharing of mitochondrial lineage with Caucasians

Inder singh, Sunil Sakhya, Madhuri Behari, M.V. Padma Srivastava, Garima Shukla, Vinay Goyal, Achal Kumar Srivastava, Mohd. Faruq, Parkinsonism & Related Disorders, Volume 22, Supplement 2, January 2016, Page e154, ISSN 1353-8020, doi: 10.1016/j.parkreldis.2015.10.360.

Compound heterozygous FXN mutations and clinical outcome in Friedreich ataxia

Charles A. Galea, Aamira Huq, Paul J. Lockhart, Geneieve Tai, Louise A. Corben, Eppie M. Yiu, Lyle C. Gurrin, David R. Lynch, Sarah Gelbard, Alexandra Durr, Francoise Pousset, Michael Parkinson, Robyn Labrum, Paola Giunti, Susan L. Perlman, Martin B. Delatycki and Marguerite V. Evans-Galea; Annals of Neurology Accepted manuscript online: 24 DEC 2015 DOI: 10.1002/ana.24595

This integrated analysis of categorized frataxin mutations and their correlation with clinical outcome provides a definitive resource for investigating disease pathogenesis in FRDA

Diagnosis and management of hypertrophic cardiomyopathy

Antonis Pantazis MD, Annina S Vischer MD, Maria Carrillo Perez-Tome MD and Silvia Castelletti MD;  Echo Res Pract. 2015 Mar 1;2(1):R45-53. doi: 10.1530/ERP-15-0007. Epub 2015 Mar 11.

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Friedreich Ataxia:  Histological features explain that the hypertrophy derives from a striking proliferation of mitochondria within the cardiomyocytes, and a marked loss of contractile fibres. The cardiac involvement is high (more than 60% of patient affected) and usually asymptomatic.

European medical research escapes stifling privacy laws

Alison Abbott. Nature, Breaking News. doi:10.1038/nature.2015.19054 16 December 2015

Proposed legislation had threatened the use of genomic and clinical data in medical studies.

Longitudinal magnetic resonance imaging study shows progressive pyramidal and callosal damage in Friedreich's ataxia

Thiago J.R. Rezende Msc, Cynthia B. Silva MD, PhD, Clarissa L. Yassuda MD, PhD, Brunno M. Campos Msc, Anelyssa D'Abreu MD, PhD, Fernando Cendes MD, PhD, Iscia Lopes-Cendes MD PhD andMarcondes C. França Jr. MD, PhD; Mov Disord. 2015 Dec 21. doi: 10.1002/mds.26436. [Epub ahead of print]

Patients with Friedreich’s ataxia present more widespread gray and white matter damage than previously reported, including not only infratentorial areas, but also supratentorial structures.

The novel triterpenoid RTA 408 protects human retinal pigment epithelial cells against H2O2-induced cell injury via NF-E2-related factor 2 (Nrf2) activation

Xiaobin Liu, Keith Ward, Christy Xavier, Jamieson Jann, Abbot F. Clark, Iok-Hou Pang, Hongli Wu, Redox Biology, Available online 19 December 2015, ISSN 2213-2317, doi:10.1016/j.redox.2015.12.005.

Study about RTA 408 for degenerative eye diseases. Currently there is an ongoing clinical trial for the FA. Although the work is focused on age-related macular degeneration, includes important insights on the action mechanism of RTA 408.

RTA 408 represents a novel class of therapeutics that has the potential to increase Nrf2 expression and thereby increase expression of antioxidant enzymes. RTA 408 is a member of the synthetic oleanane triterpenoid compounds. It is currently under clinical investigation for the prevention of cataract surgery-induced loss of corneal endothelial cells, prevention of radiation-induced dermatitis in breast cancer patients undergoing radiotherapy, treatment of solid tumors including melanoma and lung cancer, and treatment of Friedreich’s Ataxia and mitochondrial myopathies. The present study investigates the connection between RTA 408 and the Nrf2 pathway as well as multiple antioxidant enzymes in RPE cells. This will help determine whether RTA 408 may serve as a potent therapy for AMD and other degenerative eye diseases.

Functional and gait assessment in children with Friedreich ataxia: Comparison of quantitative and functional evaluation

G. Vasco, M. Petrarca, S. Gazzellini, M.L. Lispi, G. Della Bella, S. Carniel, M. Zazza, E. Castelli, E. Bertini; Gait & Posture, Volume 42, Supplement 3, December 2015, Pages S45-S46, ISSN 0966-6362, doi: 10.1016/j.gaitpost.2015.03.083.

The spatial and temporal parameters revealed to be the most sensitive quantitative indicators and have a good correlation with SARA.