Transplanted Neurons Develop Disease-like Pathology In Huntington's Patients

ScienceDaily (July 20, 2009) — The results of a recent study published in the Proceedings of the National Academy of Sciences question the long-term effects of transplanted cells in the brains of patients suffering from Huntington's disease.

Other source: http://www.eurekalert.org/pub_releases/2009-07/ul-tnd071609.php

Original work which explains the test:

Transplanted fetal striatum in Huntington's disease: Phenotypic development and lack of pathology

Thomas B. Freeman,^abcde Francesca Cicchetti,^df Robert A. Hauser,^bcg Terrence W. Deacon,^f Xiao-Jiang Li,^h Steven M. Hersch,ⁱ G. Michael Nauert,^j Paul R. Sanberg,^abc Jeffrey H. Kordower,^k Samuel Saporta,^acl and Ole Isacson^ef

^aDepartment of Neurosurgery,^bDepartment of Pharmacology and Experimental Therapeutics, and, ^cThe Neuroscience Program, University of South Florida, Tampa, FL 33606; Departments of, ^gNeurology and, ^lAnatomy,^jWomen's Center, Tampa, FL 33606;^kDepartment of Neurological Sciences, Rush Presbyterian Medical Center, Chicago, IL 60612;^fNeuroregeneration Laboratory, McLean Hospital/MGH, Harvard Medical School, Belmont, MA 62478; and Departments of, ^hGenetics and, ⁱNeurology, Emory University, Atlanta, GA 30322

^dT.B.F. and F.C. contributed equally to this work.

^eTo whom reprint requests should be addressed: T.B.F. (phone: 813-259-0889; fax: 813-259-0944; E-mail: tfreeman@com1.med.usf.edu) or O.I. (E-mail: isacson@helix.mgh.harvard.edu).

Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved October 12, 2000

Received July 13, 2000.

Penwest Announces Results of Phase Ib Trial of A0001

GlobeNewswire
Source: Penwest Pharmaceuticals Co.

In the Phase Ib trial, the drug was well tolerated by subjects, and no serious adverse events were reported. There was a dose-dependent increase in exposure approaching steady state within 2-4 days following repeat-dosing, and a maximum tolerated dose was established.

Plans to Advance A0001 Into Phase IIa Trials in Patients in Second Half of 2009

http://www.penw.com/

http://health.groups.yahoo.com/group/FA_babelFAmily/message/3058

UA Professors receive over $1.45 million in grants

Money to fund researching neurological diseases
The Crimson White, Published: Thursday, July 16, 2009
.../...
While they are researching different topics, both professors are focusing on certain proteins found in the body and their roles in neurological diseases. Busenlehner’s research focuses on a neurodegenerative disease called Friedreich’s ataxia, which is caused by decreased levels of the protein frataxin.
“What we are wanting to know is what is the exact function of this protein, frataxin, in the human body,” Busenlehner said.
.../...

Huntington's: Researchers Gain Insight Into Mechanism Underlying The Disease

Medical News Today , Article Date: 15 Jul 2009 - 0:00 PDT

Researchers at the University of Kentucky Markey Cancer Center and Graduate Center for Toxicology (GCT) have gained new insight into the genetic mechanisms underlying Huntington's disease and other neurodegenerative or neuromuscular disorders caused by trinucleotide repeats (or TNRs) in DNA.



This newspaper article is based on this research: http://friedreichscientificnews.blogspot.com/2009/07/incision-dependent-and-error-free.html

Incision-dependent and error-free repair of (CAG)(n)/(CTG)(n) hairpins in human cell extracts

Nat Struct Mol Biol. 2009 Jul 13

Hou C, Chan NL, Gu L, Li GM.
Graduate Center for Toxicology and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, USA.

Keywords: Expansion of CAG/CTG trinucleotide repeats, neurological disorders, Huntington's disease, proliferating cell nuclear antigen (PCNA), endonuclease activities, trinucleotide repeat instability.

[Diseases caused by triplet expansion.]

Rev Neurol. 2009 Jul 16-31;49(2):79-87

[Article in Spanish]
Rosales-Reynoso MA, Ochoa-Hernandez AB, Barros-Nunez P.
Centro de Investigacion Biomedica de Occidente IMSS (CIBO), Guadalajara, Mexico

Keywords: expansion of nucleotide triplets, meiosis, mitosis, CGG/ GCC, CAG/GTC, CTG/GAC, GAA/CTT, bulbospinal muscular atrophy, Huntington's diseas, spinocerebellar ataxias, fragile X syndrome, Friedreich's ataxia, myotonic dystrophy, cis-acting, trans-acting, pre-mutations, dynamic mutation processes.

Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathy

OPEN ACCES

Min-Suk Yoon , Zaza Katsarava , Mark Obermann , Maria Schaefers , Bernd Liedert , Anna Dzagnidze , Andreas Kribben , Rupert Egensperger , Volker Limmroth , Hans Christoph-Diener and Juergen Thomale
BMC Neuroscience 2009, 10:77doi:10.1186/1471-2202-10-77
Published:
15 July 2009
Abstract (provisional)
Background
Cisplatin mediates its antineoplastic activity by formation of distinct DNA intrastrand cross links. The clinical efficacy and desirable dose escalations of cisplatin are restricted by the accumulation of DNA lesions in dorsal root ganglion (DRG) cells leading to sensory polyneuropathy (PNP). We investigated in a mouse model by which mechanism recombinant erythropoietin (rhEPO) protects the peripheral nervous system from structural and functional damage caused by cisplatin treatment with special emphasis on DNA damage burden.
Results
A cumulative dose of 16 mg cisplatin/kg resulted in clear electrophysiological signs of neuropathy, which were significantly attenuated by concomitant erythropoietin (cisplatin 32,48 m/s +/- 1,68 m/s; cisplatin + rhEPO 49,66 m/s +/- 1,26 m/s; control 55,01 m/s +/- 1,88 m/s; p < 0,001). The co-application of rhEPO, however, did not alter the level of unrepaired cisplatin-DNA lesions accumulating in DRG target cells. Micro-morphological analyses of the sciatic nerve from cisplatin-exposed mice showed damaged myelin sheaths and mitochondria. Co-administered rhEPO inhibited myelin sheaths from structural injuries and resulted in an increased number of intact mitochondria.
Conclusion
The protective effect of recombinant erythropoietin is not mediated by reducing the burden of DNA platination in the target cells, but it is likely to be due to a higher resistance of the target cells to the adverse effect of DNA damage. The increased frequency of intact mitochondria might also contribute to this protective role.

Full text: http://www.biomedcentral.com/content/pdf/1471-2202-10-77.pdf

Abnormal Left Atrial Contraction in Friedreich Ataxia—Relation with Both Alleles of the FXN Gene

Heart, Lung and Circulation
Volume 18, Supplement 3, 2009, Page S15
Abstracts for the Cardiac Society of Australia and New Zealand Annual Scientific Meeting and the International Society for Heart Research, Australasian Section, Annual Scientific Meeting

R.E. Peverill^1, , L. Donelan¹, J.S. Gelman¹, P.M. Mottram¹, L.A. Corben² and M.B. Delatycki²

¹Monash Cardiovascular Research Centre, MonashHEART and Monash University Department of Medicine (MMC), Australia

²Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Melbourne, Australia

The role of PGC-1{alpha} on mitochondrial function and apoptotic susceptibility in muscle

Peter J. Adhihetty,² Giulia Uguccioni,^1,3 Lotte Leick,⁴ Juan Hidalgo,⁵ Henriette Pilegaard,⁴ and David A. Hood^1,2,3

¹School of Kinesiology and Health Science, ²Department of Biology, and ³The Muscle Health Research Centre, York University, Toronto, Ontario, Canada; ⁴Copenhagen Muscle Research Centre and Centre of Inflammation and Metabolism, Department of Biology, University of Copenhagen, Denmark, and ⁵Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Autonomous University of Barcelona, Barcelona, Spain

Submitted 12 February 2009 ; accepted in final form 5 May 2009

Keywords: endurance training; exercise; mitochondrial biogenesis; reactive oxygen species, cytochrome-c oxidase activity, brain, liver, pancreas.

Mitochondrial Dysfunction Leads to Nuclear Genome Instability via an Iron-Sulfur Cluster Defect

Joshua R. Veatch1, 2, Michael A. McMurray1, 2, 3, Zara W. Nelson1 and Daniel E. Gottschling1, ,
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109, USA
2The Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98109, USA
3Present address: Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA
Received 14 September 2008; revised 30 January 2009; accepted 1 April 2009. Published: June 25, 2009. Available online 25 June 2009

Keywords; nuclear genome, genome instability, mitochondrial membrane potential, iron-sulfur cluster. a



Friedreich's Ataxia - Frataxin