Circulating miR-323-3p is a biomarker for cardiomyopathy and an indicator of phenotypic variability in Friedreich’s ataxia patients

M. Seco-Cervera, D. González-Rodríguez, J. S. Ibáñez-Cabellos, L. Peiró-Chova, P. González-Cabo, E. García-López, J. J. Vílchez, I. Sanz-Gallego, F. V. Pallardó & J. L. García-Giménez; Scientific Reports 7, Article number: 5237 (2017) doi:10.1038/s41598-017-04996-9

miR-323a-3p as a biomarker for diagnosis of cardiomyopathy in FRDA

Circulating miRNAs can detect pathological events, and could also monitor molecular signals participating in cardiomyopathy even before the appearance of clinical cardiac manifestations. To maximize the likelihood of detecting the onset or progression of cardiomyopathy, we suggest combining standard cardiac diagnostic procedures with the use of circulating microRNAs. This approach could provide more clinical information for evaluating cardiomyopathy progression in FRDA. In summary, miRNAs obtained in this study show new candidates for personalized therapy in FRDA patients.

How does performance of the Friedreich Ataxia Functional Composite compare to rating scales?

Geneieve Tai, Eppie M. Yiu, Martin B. Delatycki, Louise A. Corben; J Neurol (2017). doi:10.1007/s00415-017-8566-0

The aims of this study were to examine the relationship between the Friedreich Ataxia Functional Composite (FAFC) measures and characteristics of FRDA to determine if the FAFC is more sensitive to clinical change over time compared to its components.

Drosophila melanogaster Models of Metal-Related Human Diseases and Metal Toxicity

Pablo Calap-Quintana, Javier González-Fernández, Noelia Sebastiá-Ortega, José Vicente Llorens, Orcid and María Dolores Moltó; Int. J. Mol. Sci. 2017, 18(7), 1456; doi:10.3390/ijms18071456

Drosophila models of FRDA support the proposal that iron plays a major role in FRDA physio-pathology. Although reduction in iron levels by iron chelation has been relatively successful in clinical trials, genetic or pharmacological intervention through the sphingolipid/Pdk1/Mef-2 pathway and pathways regulating iron homeostasis are new approaches to be explored in preclinical studies.

Selected missense mutations impair frataxin processing in Friedreich ataxia

Elisia Clark, Jill S. Butler, Charles J. Isaacs, Marek Napierela and David R. Lynch; Annals of Clinical and Translational Neurology. doi: 10.1002/acn3.433

FXNI154F and FXNG130V missense mutations decrease FXN81–210 levels compared with FXNWT, FXNR165C, and FXNW155R, but do not block its association with mitochondria. FXNI154F and FXNG130V also impair FXN maturation and enhance the binding between FXN42–210 and mitochondria processing peptidase. Furthermore, blocking proteosomal degradation does not increase FXN81–210 levels. Additionally, impaired FXN processing also occurs in fibroblasts from patients with FXNG130V. Finally, clinical data from patients with FXNG130V and FXNI154F mutations demonstrates a lower severity compared with other individuals with Friedreich ataxia.

Friedreich’s ataxia associated with marfanoid features & alopecia areata-rare disease manifestations or chance association?

Chandramohan Sharma, Banshilal Kumawat, Maulik Panchal, Kaushik Rana, Indian Journal of Medical Specialities, Available online 19 June 2017, ISSN 0976-2884, doi:10.1016/j.injms.2017.06.005.

Apart from neurological features it has cardiac, skeletal and endocrine manifestations but its association with marfanoid features and/or alopecia areata have not been described in literature.

Cerebellar ataxia and intrathecal baclofen therapy: Focus on patients´ experiences

Berntsson SG, Landtblom A-M, Flensner G; PLoS ONE 12(6): e0180054. https://doi.org/10.1371/journal.pone.0180054

Elucidating patients´ experiences of living with chronic progressive hereditary ataxia and the symptomatic treatment with intrathecal baclofen (ITB) is the objective of the current study. A multicenter qualitative study with four patients included due to the rare combination of hereditary ataxia and ITB therapy was designed to elucidate participants’ experiences through semi-structured interviews. The transcribed text was analyzed according to content analysis guidelines. Overall we identified living in the present/ taking one day at a time as the main theme covering the following categories: 1) Uncertainty about the future as a consequence of living with a hereditary disease; The disease; 2) Impact on life as a whole, 3) Influence on personal life in terms of feeling forced to terminate employment, 4) Limiting daily activities, and 5) ITB therapy, advantages, and disadvantages. Uncertainty about the future was the category that affected participants’ personal life, employment, and daily activities. The participants’ experience of receiving ITB therapy was expressed in terms of improved quality of life due to better body position and movement as well as better sleep and pain relief.

Reata Pharmaceuticals, Inc. Receives Orphan Drug Designation For Omaveloxolone For The Treatment Of Friedreich’s Ataxia

RVING, Texas, June 22, 2017 (GLOBE NEWSWIRE) -- Reata Pharmaceuticals, Inc. (Nasdaq:RETA) (“Reata” or “the Company”), a clinical-stage biopharmaceutical company, today announced the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to omaveloxolone for the treatment of Friedreich’s ataxia.
"Orphan drug designation serves as an important milestone for our company as it recognizes the promise of omaveloxolone as a potential new treatment for FA. In light of the recent, encouraging clinical data, we are hopeful that omaveloxolone will be the first therapy approved for patients with FA," said Warren Huff, Chief Executive Officer of Reata.

Muscle ultrasound comparison between patients with early and delayed onset Friedreich's ataxia – Preliminary data

R.J. Verbeek, A.J.E. Waalkens, M.J. Kuiper, C.C. Verschuuren-Bemelmans, J.H. van der Hoeven, J.J. de Vries, J. van Gaalen, M.A.A.P. Willemsen, H.P.H. Kremer, D.A. Sival, European Journal of Paediatric Neurology, Volume 21, Supplement 1, June 2017, Page e234, ISSN 1090-3798, doi:10.1016/j.ejpn.2017.04.1259.

Muscle ultrasound density leg-muscle parameters are substantially higher in d-FA than healthy subjects, but do not reveal a discriminative pattern between d-FA and p-FA phenotypes. This could be attributed to the large proportion of d-FA patients with an intermediate (mildly-delayed) age of onset (17-25 years, n=7/8 (88%)) and to the cross-sectional nature of the study. These findings implicate that p-FA and “intermediate-d-FA” muscle ultrasound outcomes refer to a similar neuro-muscular spectrum rather than distinctly different neuromuscular phenotypes.

Genotype-phenotype correlation in Friedreich's ataxia

G. Kovacevic, S. Todorovic, I. Novakovic, D. Pavicevic Savic, V. Milic Rasic, M. Svetel, V. Dobricic; European Journal of Paediatric Neurology Volume 21, Supplement 1, June 2017, Pages e205–e206, doi:10.1016/j.ejpn.2017.04.1083


Contrary to other published studies we didn’t find any significant correlation between the age of onset and the GAA1 size. Two possible explanation could be the relative small number of patients in our study as well as the small differences in alleles size and age of onset between the patients. We found a correlation between the size of the smaller allele and extensor plantar response and between the size of the larger allele (GAA2) and impaired vibration sense. The duration of the disease is correlated european journal of paediatric neurology 21 (2017) e197 ee213 e205 with presence of nystagmus, foot deformities, upper limb areflexia, dysarthria and ECG abnormality.

Lower medulla hypoplasia in Friedreich ataxia: MR Imaging confirmation 140 years later

Mario Mascalchi, Andrea Bianchi, Stefano Ciulli, Andrea Ginestroni, Marco Aiello, Maria Teresa Dotti, Fabrizio Salvi, Emanuele Nicolai, Andrea Soricelli, Stefano Diciotti; Neurol (2017). doi:10.1007/s00415-017-8542-8 DOI: 10.1007/s00415-017-8542-8

Hence ataxia in the disease described by Friedreich may be due to two components: a mal-developmental one affecting spinal cord and medulla and a superimposed degenerative one affecting the cerebellar dentate.