Gene-editing tool CRISPR opens a world of possibilities for rare genetic diseases

CRISPR gene-editing tool has scientists thrilled — but nervous. By Kelly Crowe, CBC News Posted: Nov 30, 2015 5:00 AM ET

The CRISPR system allows anyone with basic molecular biology training to edit the genome with a pinpoint precision not possible before, in addition CRISPR editing is relatively cheap once established.
Much remains to be done in scientific and legal aspects, would be able to eradicate human gene mutations from all future generations?. There is also a strong ethical concern, it could be used to cure genetic diseases or also for eugenic purposes.

Access to Orphan Drugs: A Comprehensive Review of Legislations, Regulations and Policies in 35 Countries

Gammie T, Lu CY, Babar ZU-D (2015), PLoS ONE 10(10): e0140002., doi:10.1371/journal.pone.0140002

OPEN ACCESS

Access to orphan drugs depends on individual country’s pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access.
Overall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented.

Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots

Shao-Hua Yang, Wenjun Li, Nathalie Sumien, Michael Forster, James W. Simpkins, Ran Liu, Progress in Neurobiology, Available online 18 November 2015, ISSN 0301-0082, doi:10.1016/j.pneurobio.2015.10.005

There is accumulating evidence providing a proof of concept that enhancement of mitochondrial oxidative phosphorylation via alternative mitochondrial electron transfer may offer protective action against neurodegenerative diseases and inhibit cancers proliferation.

Retrotope announces opening of second clinical trial site for enrollment in Friedreich's ataxia clinical trial

LOS ALTOS, Calif., Nov. 20, 2015 /PRNewswire/ -- Retrotope announces the opening of second clinical trial site, the Collaborative Neuroscience Network, LLC. ("CNS") in Long Beach, California, for the ongoing 28-day, first-in-human randomized, double-blind, controlled, ascending dose study of orally dosed RT001 to evaluate the safety, tolerability, pharmacokinetics (PK), disease state, and exploratory endpoints in patients with Friedreich's ataxia (FA).

Frataxin expression in reticulocytes of non-splenectomized and splenectomized patients with HbE-β-thalassaemia

Yollada Suebpeng, Arunee Jetsrisuparb, Supan Fucharoen, Amporn Tripatara, Clinical Biochemistry, Available online 14 November 2015, ISSN 0009-9120, doi: 10.1016/j.clinbiochem.2015.11.008.

The relative FXN expression in the patients was found to be correlated with the levels of MDA and ferritin but not correlated with transferrin saturation. The elevation of FXN expression in the reticulocytes of these patients seems to be linked to oxidative stress and iron status. Findings also suggest that FXN expression is at least partially regulated by the mitochondrial demand for iron for haem synthesis.

Efficient attenuation of Friedreich's ataxia (FRDA) cardiomyopathy by modulation of iron homeostasis-human induced pluripotent stem cell (hiPSC) as a drug screening platform for FRDA,

Yee-Ki Lee, Yee-Man Lau, Kwong-Man Ng, Wing-Hon Lai, Shu-Leong Ho, Hung-Fat Tse, Chung-Wah Siu, Philip Wing-Lok Ho, International Journal of Cardiology, Available online 17 November 2015, ISSN 0167-5273, doi:10.1016/j.ijcard.2015.11.101.

Life without Fe-S clusters

Agostinho G. Rocha and Andrew Dancis, Molecular Microbiology 1365-2958, DOI - 10.1111/mmi.13273

Microcommentary on “Novel features of the ISC machinery revealed by characterization of Escherichia coli mutants that survive without iron-sulfur clusters” by Naoyuki Tanaka, Miaki Kanazawa, Keitaro Tonosaki, Nao Yokoyama, Tomohisa Kuzuyama, Yasuhiro Takahashi.

Développement d'un nouveau modèle cellulaire de l'ataxie de Friedreich : différenciation de cellules pluripotentes induites de patients en cardiomyocytes

Aurore Hick. (Theses) Rhumatologie et système ostéo-articulaire. Université de Strasbourg, 2014. Français.

Frataxin knockdown in Drosophila alters mitochondrial homeostasis and degradation in muscles and glia

Seminars: IGC - Instituto Gulbenkian de Ciência (Portugal), Speaker: Juan Navarro, Affiliation: Institut für Zoologie, Universität Regensburg, Germany, Date 13/11/2015

Normative Data for an Instrumental Assessment of the Upper-Limb Functionality

Marco Caimmi, Eleonora Guanziroli, Matteo Malosio, Nicola Pedrocchi, Federico Vicentini, Lorenzo Molinari Tosatti and Franco Molteni, BioMed Research International Volume 2015 (2015), Article ID 484131, 14 pages doi:10.1155/2015/484131


This work led to the creation of a reliable database of normative data of the Reaching and Hand-to-Mouth Evaluation Method. Its simplicity and brevity make the whole procedure widely applicable to the UL functional assessment.

Structural and Functional Magnetic Resonance Imaging of the Cerebellum: Considerations for Assessing Cerebellar Ataxias

Andreas Deistung , Maria R. Stefanescu, Thomas M. Ernst, Marc Schlamann, Mark E. Ladd, Jürgen R. Reichenbach, Dagmar Timmann, Review: The Cerebellum pp 1-5 First online: 31 October 2015 DOI 10.1007/s12311-015-0738-9

Data from initial fMRI studies are presented in three common forms of hereditary ataxias (Friedreich’s ataxia, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6).

Patent: METHODS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT AND THE PREVENTION OF CARDIOMYOPATHY DUE TO FRIEDREICH ATAXIA

Inventor(s): PUCCIO HELENE MONIQUE [FR]; AUBOURG PATRICK [FR]; CRYSTAL RONALD G [US]; BOUGNERES PIERRE [FR]

Application number: US201514718696 20150521

A method for preventing or treating cardiomyopathy due to energy failure in a subject in need thereof is provided. The method comprises administering to the subject a therapeutically effective amount of a vector which comprises a nucleic acid sequence encoding a gene that can reverse energy failure. An exemplary cardiomyopathy is that which is associated with Friedreich ataxia and an exemplary nucleic acid sequence comprises a nucleic acid that encodes frataxin (FXN).

Management of Children with Mild, Moderate, and Moderately Severe Sensorineural Hearing Loss

Anne Marie Tharpe, Samantha Gustafson, Otolaryngologic Clinics of North America, Volume 48, Issue 6, December 2015, Pages 983-994, ISSN 0030-6665, doi:10.1016/j.otc.2015.07.005.

The roles of pediatricians and otolaryngologists in referring children for appropriate assessments and interventions, and encouraging families to comply with hearing technology use and therapeutic intervention are crucial to ensuring the best possible outcomes.

UAB researchers seek Friedreich’s ataxia biomarkers

UAB News, University of Alabama at Birmingham, November 04, 2015

“There is a high demand for biomarkers because of ongoing clinical trials with Friedreich’s ataxia patients,” said Marek Napierala, Ph.D., assistant professor in UAB Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute. “We need better measures of the progression of the disease and the therapeutic response.”

Safety, Tolerability and Efficacy of ACTIMMUNE Dose Escalation in Friedreich's Ataxia Study

ClinicalTrials.gov Identifier: NCT02593773, First received: October 29, 2015

 The purpose of this phase 3 multi-center, open-label extension study is to evaluate the long-term safety of ACTIMMUNE (interferon-γ 1b) in subjects with Friedreich's Ataxia (FA).

Drug: Interferon γ-1b, Other Name: ACTIMMUNE

Approximately 90 subjects will receive subcutaneous (SC) doses of ACTIMMUNE three times a week (TIW) for a total of 26 weeks. The study drug dose is planned to be escalated on a weekly basis over the first 4 weeks of treatment (from 10 µg/m² to 25, 50, and 100 µg/m²). The dose may be reduced, interrupted, or held based on tolerability. By week 13, all subjects are to be on a stable tolerated dose of study drug in order to continue study participation; the dose may not be further increased after week 13, however, it may be reduced on a case-by-case basis to manage drug-related AEs.

Frataxin Is Localized to Both the Chloroplast and Mitochondrion and Is Involved in Chloroplast Fe-S Protein Function in Arabidopsis.

Turowski VR, Aknin C, Maliandi MV, Buchensky C, Leaden L, Peralta DA, Maria V. Busi, Alejandro Araya, Diego F. Gomez-Casati, PLoS ONE 10(10): e0141443. doi:10.1371/journal.pone.0141443

A personal perspective of orphan drug development for rare diseases: A golden opportunity or an unsustainable future?

Oo, C. and Rusch, L. M. Journal of Clinical Pharma. doi: 10.1002/jcph.599

Nevertheless, there is no better opportunity than the present to develop orphan drugs in order to accelerate the treatment and alleviate the suffering of patients with rare diseases.