Progress and prospects: stem cells and neurological diseases

Gene Therapy , (30 September 2010) | doi:10.1038/gt.2010.130

S Gögel, M Gubernator and S L Minger

Review.

Keywords: central nervous system, degenerative neurological conditions, Parkinson's disease (PD), Alzheimer's disease, Huntington's disease (HD), cerebrovascular damage (for example, stroke), spinal cord injury, transplantation of stem cells, stem cell-derived progenitors, induced pluripotent stem cells.

Spinal convergence of motor and sensory pathways

Nature Neuroscience 13, 1160 (2010)
Published online: 27 September 2010 | doi:10.1038/nn1010-1160

Min Cho

KEYWORDS: motor execution, proprioceptive sensory feedback, motor command.

Human frataxin is an allosteric switch that activates the Fe-S cluster biosynthetic complex

Biochemistry, Just Accepted Manuscript
Publication Date (Web): September 27, 2010

Chi-Lin Tsai and David P. Barondeau, Department of Chemistry, Texas A&M
University, College Station, TX 77842, USA.

Full text pdf

Scientists Discover Gene That Controls Stem Cells In Central Nervous System

Medical News Today, 27 Sep 2010

"With the knowledge that the gene Sox9 plays a central role in the development of our nervous system, we are one step closer to being able to control stem cells in the brain and regenerate different kinds of nerve cells." ....read more....

Restless Legs and Substantia Nigra Hypoechogenicity are Common Features in Friedreich's Ataxia.

Cerebellum. 2010 Sep 24.

Synofzik M, Godau J, Lindig T, Schöls L, Berg D.

Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany.

KEYWORDS: Friedreich's ataxia (FA), restless legs syndrome (RLS), multisystemic network dysfunction, peripheral neuropathy, disturbances in subcellular brain iron homeostasis.

Combined Therapy with Idebenone and Deferiprone in Patients with Friedreich's Ataxia.

Cerebellum. 2010 Sep 24.

Velasco-Sánchez D, Aracil A, Montero R, Mas A, Jiménez L, O'Callaghan M, Tondo M, Capdevila A, Blanch J, Artuch R, Pineda M.

Cardiology Department, Sant Joan de Déu Hospital and the University of Barcelona, 2, Passeig Sant Joan de Déu, 08950 Esplugues, Barcelona, Spain

KEYWORDS: Iron chelators,Friedreich's ataxia, mitochondrial iron pools, neurological signs, cardiac function parameters, prospective open-label single-arm study, idebenone (20 mg/kg/day), deferiprone (20 mg/kg/day), International Cooperative Ataxia Rating Scale (ICARS) scores, echocardiographic measurements, MRI (magnetic resonance imaging) techniques, neutropenia, progressive reduction of plasma iron parameters.

Auszeichnung für neuen Therapieansatz bei Morbus Friedreich an MedUni Wien

Medizinische Universität Wien

(Wien, 21-09-2010) Barbara Scheiber-Mojdehkar und Brigitte Sturm vom Zentrum für Pathobiochemie und Genetik der MedUni Wien haben einen völlig neuen Therapieansatz zur Behandlung der neurodegenerativen Krankheit Friedreichs Ataxie entdeckt und dafür die Goldmedaille bei der Korea International Women`s Invention Exposition KIWIE 2010 erhalten. Heute fand die Überreichung durch Bundesministerin Dr.in Beatrix Karl statt.

"Award for new approach in the treatment of Friedreich's Disease by Medical University of Vienna"

Keyword: Iron chelators, neurodegenerative disease, Friedreich's ataxia, mitochondrial protein frataxin, erythropoietin.

The Impact of the Orphan Drug Act on the Development and Advancement of Neurological Products for Rare Diseases: A Descriptive Review

Clinical Pharmacology & Therapeutics (2010) 88 4, 449–453. doi:10.1038/clpt.2010.193

K A Burke1, S N Freeman1, M A Imoisili1 and T R Coté1
1Office of Orphan Products Development, US Food and Drug Administration, Silver Spring, Maryland, USA

Successful treatment of auditory perceptual disorder in individuals with Friedreich ataxia

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0F-511K412-6&_user=10&_coverDate=09%2F16%2F2010&_rdoc=1&_fmt=high&_orig=browse&_origin=browse&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=2cce40ce235d6a2b6e7401ca8adce6ff


Neuroscience, In Press, Uncorrected Proof, Available online 16 September 2010,doi:10.1016/j.neuroscience.2010.09.013

G. Rance a, L.A. Corben b, E. Du Bourg a, A. King c and M.B. Delatycki b

a Department of Otolaryngology, The University of Melbourne, Parkville, Victoria, Australia

b Bruce Lefroy Centre for Genetic Health Research, Parkville, Victoria, Australia

c Australian Hearing, Parkville, Victoria, Australia


Keywords: Friedreich's ataxia; auditory neuropathy; auditory processing; speech perception, personal-FM systems, communication difficulties.

Creating a global rare disease patient registry linked to a rare diseases biorepository database: Rare Disease-HUB (RD-HUB)☆

Contemporary Clinical Trials - September 2010 (Vol. 31, Issue 5, Pages 394-404, DOI: 10.1016/j.cct.2010.06.007)

Yaffa R. Rubinsteina, Stephen C. Grofta23, Ronald Bartekb, Kyle Brownc, Ronald A. Christensend, Elaine Colliere, Amy Farberf, Jennifer Farmerb, John H. Fergusona, Christopher B. Forrestgh, Nicole C. Lockharti, Kate R. McCurdyj, Helen Moorei, Geraldine B. Pollena, Rachel Richessonk, Vanessa Rangel Millerl, Sara Hullm, Jim Vaughti

a Office of Rare Diseases Research National Institutes of Health, Bethesda, MD, United States

b Friedreich's Ataxia Research Alliance (FARA), Springfield, VA, United States

c Innolyst, Inc, San Mateo, CA, United States

d REGISTRAT-MAPI, Scottsdale, AZ, United States

e National Center for Research Resources, National Institutes of Health, Bethesda, MD, United States

f LAM Treatment Alliance, Cambridge, MA, United States

g Children's Hospital of Philadelphia, Philadelphia, PA, United States

h Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, United States

i Office of Biorepositories and Biospecimen Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States

j Barth Syndrome Foundation, Inc, Larchmont, NY, United States

k Department of Pediatrics, Division of Bioinformatics and Biostatistics, University of South Florida College of Medicine, Tampa, FL, United States

l Department of Human Genetics, Emory University, Atlanta, GA, United States

m Office of the Clinical Director, National Human Genome Research Institute, Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, MD, United States

☆ Authors listed 3rd to18th alphabetically contributed equally.

1 Director of Patient Resources for Clinical and Translational Research, Office of Rare Dieseases Reseach.

2 Director of the Office of Rare Diseases Research, National Institutes of Health, 6100 Executive Boulevard, Room 3A07, MSC-751, Bethesda, MD 20892, United States. Tel.: +1 301 435 6041.

3 Co-first author.

Keywords: FARA, Rare diseases, Patient registry, Disease registry, Patient advocacy, Biospecimen, Biospecimen repositories, Clinical data, Electronic health record

Long-Term IGF-I Exposure Decreases Autophagy and Cell Viability

PLoS One. 2010; 5(9): e12592.
Published online 2010 September 7. doi: 10.1371/journal.pone.0012592.

Alessandro Bitto,1 Chad Lerner,1 Claudio Torres,1 Michaela Roell,2 Marco Malaguti,2 Viviana Perez,3 Antonello Lorenzini,1,2 Silvana Hrelia,3 Yuji Ikeno,4 Michelle Elizabeth Matzko,5 Roger McCarter,4 and Christian Sell1*
1Department of Pathology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America
2Department of Biochemistry, “G. Moruzzi” University of Bologna, Bologna, Italy
3Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America
4Barshop Institute for Longevity and Aging Studies and Department of Pathology, University of Texas Health Science Center at San Antonio, Research Service, Audie Murphy VA Hospital (STVHCS), San Antonio, Texas, United States of America
5Department of Biobehavioral Health, Penn State University, State College, Pennsylvania, United States of America
Matt Kaeberlein, Editor
University of Washington, United States of America


Abstrac

A reduction in IGF-I signaling has been found to increase lifespan in multiple organisms despite the fact that IGF-I is a trophic factor for many cell types and has been found to have protective effects against multiple forms of damage in acute settings. The increase in longevity seen in response to reduced IGF-I signaling suggests that there may be differences between the acute and chronic impact of IGF-I signaling. We have examined the possibility that long-term stimulation with IGF-I may have a negative impact at the cellular level using quiescent human fibroblasts. We find that fibroblast cells exposed to IGF-I for 14 days have reduced long-term viability as judged by colony forming assays, which is accompanied by an accumulation of senescent cells. In addition we observe an accumulation of cells with depolarized mitochondria and a reduction in autophagy in the long-term IGF-I treated cultures. An examination of mice with reduced IGF-I levels reveals evidence of enhanced autophagy and fibroblast cells derived from these mice have a larger mitochondrial mass relative to controls indicating that changes in mitochondrial turnover occurs in animals with reduced IGF-I. The results indicate that chronic IGF-I stimulation leads to mitochondrial dysfunction and reduced cell viability.

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Characterization of the human HSC20, an unusual DnaJ type III protein, involved in iron–sulfur cluster biogenesis

Hum. Mol. Genet. (2010) doi: 10.1093/hmg/ddq301

Helge Uhrigshardt 1,2,Anamika Singh 1,Gennadiy Kovtunovych 1,Manik Ghosh 1 and Tracey A. Rouault 1.

1 Molecular Medicine Program, The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA and 2.JHU-Bayview Proteomics Center, Johns Hopkins University, School of Medicine, 5200 Eastern Avenue, Baltimore, MD 21224, USA

The Friedreich’s Ataxia protein frataxin modulates DNA base excision repair in prokaryotes and mammals

Biochem. J. (2010) Immediate Publication, doi:10.1042/BJ20101116

René Thierbach, Gunnar Drewes, Markus Fußer, Anja Voigt, Doreen Kuhlow, Urte Blume, Tim J Schulz, Carina Reiche, Hansruedi Glatt, Bernd Epe, Pablo Steinberg and Michael Ristow

Department of Human Nutrition, University of Jena, Jena 07743, Germany. 

 

Keywords:  DNA repair mechanisms,  iron-sulphur-clusters (ISCs),  frataxin, Friedreich’s Ataxia,  cancer, 8-oxoguanine glycosylase.

 

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Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly

Biochemistry, Just Accepted Manuscript, DOI: 10.1021/bi1008613,Publication Date (Web): September 3, 2010

 

Jeremy D. Cook , Kalyan C. Kondapalli , Swati Rawat , William C. Childs , Yogapriya Murugesan , Andrew Dancis , and Timothy Louis Stemmler 

 

Keywords: Iron Chaperone, Frataxin, Yfh1, Isu1, Nfs1, NMR, ITC, Iron-Sulfur Cluster Assembly.

 

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Protective effects of transduced PEP-1-Frataxin protein on oxidative stress-induced neuronal cell death

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T06-50XV3JF-3&_user=10&_coverDate=09%2F03%2F2010&_rdoc=1&_fmt=high&_orig=browse&_origin=browse&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=2724eb2d4f21f0930a937b602939f104

Journal of the Neurological Sciences, In Press, Corrected Proof, Available online 3 September 2010,
Mi Jin Kim, Dae Won Kim, Ki-Yeon Yoo, Eun Jeong Sohn, Hoon Jae Jeong, Hye Won Kang, Min Jea Shin, Eun Hee Ahn, Jae Jin An, Soon Won Kwon, Young Nam Kim, Moo Ho Won, Sung-Woo Cho, Jinseu Park, Won Sik Eum and Soo Young Cho

Keywords:  Antioxidant; PEP-1-Frataxin; Protein transduction; Cell viability; Ischemia; ROS

New Research Demonstrates Safety Of Cord-blood-derived Stem Cell Treatments

Medical news Today, Article Date: 03 Sep 2010

In a new peer-reviewed article published by the Journal of Translational Medicine, scientists from Beike Biotechnology, China's leading stem cell research and regenerative medicine company, and Medistem, Inc., reported positive safety data in 114 patients who were treated by doctors at Nanshan Affiliated Hospital of Guangdong Medical College (Shenzhen Nanshan Hospital) in Shenzhen using Beike's proprietary cord blood stem cell transplantation protocol. ...read more...

Original source: Safety evaluation of allogeneic umbilical cord blood mononuclear cell therapy for degenerative conditions

Journal of Translational Medicine 2010, 8:75doi:10.1186/1479-5876-8-75

Wan-Zhang Yang1 email, Yun Zhang2 email, Fang Wu1 email, Wei-Ping Min3 email, Boris Minev4 email, Min Zhang1 email, Xiao-Ling Luo2 email, Famela Ramos5 email, Thomas E Ichim5 email, Neil H Riordan5* email and Xiang Hu2*


Background

The current paradigm for cord blood transplantation is that HLA matching and immune suppression are strictly required to prevent graft versus host disease (GVHD). Immunological arguments and historical examples have been made that the use of cord blood for non-hematopoietic activities such as growth factor production, stimulation of angiogenesis, and immune modulation may not require matching or immune suppression.

Methods

114 patients suffering from non-hematopoietic degenerative conditions were treated with non-matched, allogeneic cord blood. Doses of 1-3 × 107 cord blood mononuclear cells per treatment, with 4-5 treatments both intrathecal and intravenously were performed. Adverse events and hematological, immunological, and biochemical parameters were analyzed for safety evaluation.

Results

No serious adverse effects were reported. Hematological, immunological, and biochemical parameters did not deviate from normal ranges as a result of therapy.

Conclusion

The current hematology-based paradigm of need for matching and immune suppression needs to be revisited when cord blood is used for non-hematopoietic regenerative purposes in immune competent recipients.

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Protocol proposal for Friedreich ataxia molecular diagnosis using fluorescent and triplet repeat primed polymerase chain reaction

LINK: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B83WW-50X8GB2-1&_user=10&_coverDate=08%2F31%2F2010&_rdoc=1&_fmt=high&_orig=browse&_origin=browse&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=8b4ac06505c1ed6fa9282efeaeeed2fd

Translational Research. Article in Press.
doi:10.1016/j.trsl.2010.08.001

Mar Xunclàa, b, Laia Rodríguez-Revengaa, c, Irene Madrigala, c, Dolores Jiméneza, Montserrat Milàa, c, d and Cèlia Badenasa, c, d,

a Biochemistry and Molecular Genetics Service. Hospital Clínic, b Fundació Clínic per a la Recerca Biomèdica, c CIBER de Enfermedades Raras, d Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain