Accept Cookies?
Provided by OpenGlobal E-commerce

Please wait while your page loads ...

 

Scientific News

FARA funds research progress

In this section, you will find the most recent FA research publications, many of which are funded by FARA, as well as information on upcoming conferences and symposiums. You can search for articles by date using the archive box in the right hand column. To locate FARA Funded or Supported Research, click the hyperlink in the right hand column. You may also search for specific content using key words or phrases in the search button at the top right of your screen. Please be sure to visit other key research sections of our website for information on FARA’s Grant Program and the Treatment Pipeline.


Nanoscopic X-ray imaging and quantification of the iron cellular architecture within single fibroblasts of Friedreich's ataxia patients

In this study, the nanoscale iron distribution within single fibroblasts from Friedreich's ataxia patients was investigated using synchrotron-radiation-based nanoscopic X-ray fluorescence and X-ray in-line holography at the ID16A nano-imaging beamline of the ESRF. This unique probe was deployed to uncover the iron cellular two-dimensional architecture of freeze-dried FRDA fibroblasts. An unsurpassed absolute detection capability of 180 iron atoms within a 30 nm × 50 nm nanoscopic X-ray beam footprint was obtained using state-of-the-art X-ray focusing optics and a large-solid-angle detection system. Various micrometre-sized iron-rich organelles could be revealed for the first time, tentatively identified as endoplasmic reticulum, mitochondria and lysosomes. Also a multitude of nanoscopic iron hot-spots were observed in the cytosol, interpreted as chaperoned iron within the fibroblast's labile iron pool. These observations enable new hypotheses on the storage and trafficking of iron in the cell and ultimately to a better understanding of iron-storage diseases such as Friedreich's ataxia.

Read the entire article HERE

Age of onset determines intrinsic functional brain architecture in Friedreich ataxia

In this study the authors used magnetoencephalography (MEG) to characterize the main determinants of Friedreich ataxia (FRDA)-related changes in intrinsic functional brain architecture. Five minutes of MEG signals were recorded at rest from 18 right-handed FRDA patients (mean age 27 years, 9 females; mean SARA score: 21.4) and matched healthy individuals. The MEG connectome was estimated as resting-state functional connectivity (rsFC) matrices involving 37 nodes from six major resting state networks and the cerebellum. Source-level rsFC maps were computed using leakage-corrected broad-band (3-40 Hz) envelope correlations. Post hoc median-split was used to contrast rsFC in FRDA patients with different clinical characteristics. Nonparametric permutations and Spearman rank correlation test were used for statistics. High rank correlation levels were found between rsFC and age of symptoms onset in FRDA mostly between the ventral attention, the default-mode, and the cerebellar networks; patients with higher rsFC developing symptoms at an older age. Increased rsFC was found in FRDA with later age of symptoms onset compared to healthy subjects. No correlations were found between rsFC and other clinical parameters. This study points to age of symptom onset as a major determinant of FRDA patients' intrinsic functional brain architecture. Higher rsFC in FRDA patients with later age of symptom onset supports compensatory mechanisms for FRDA-related neural network dysfunction and position neuromagnetic rsFC as potential marker of FRDA neural reserve.

Read the entire article HERE

A new tool to determine the cellular metabolic landscape: nanotechnology to the study of Friedreich's ataxia

Understanding the cell response to oxidative stress in disease is an important but difficult task. Here, the authors demonstrate the feasibility of using a nanomotion sensor to study the cellular metabolic landscape. This nanosensor permits the non-invasive real-time detection at the single-cell level and offers high sensitivity and time resolution. The technique was optimised to study the effects of frataxin overexpression in a cellular model of Friedreich's ataxia. Previous studies had demonstrated that FXN overexpression are as toxic as silencing, thus indicating the importance of a tight regulation of the frataxin levels. The effects of frataxin overexpression was probed in the presence of oxidative stress insults and the metabolic response measured by the nanosensor. The authors show that the nanosensor provides new detailed information on the metabolic state of the cell as a function of time that agrees with and complements data obtained by more traditional techniques. The authors propose that the nanosensor can be used in the future as a new and powerful tool to study directly how drugs modulate the effects of oxidative stress on Friedreich's ataxia patients and, more in general, on other neurodegenerative processes.

Read the entire article HERE

Electrophysiological evidence for limited progression of the proprioceptive impairment in Friedreich ataxia

Cortico-kinematic coherence (CKC) is the coupling between movement-related proprioceptive inputs and the activity of the contralateral primary sensorimotor cortex activity recorded by magnetoencephalography or electroencephalography. CKC is an electrophysiological marker of spino-cortical proprioceptive function with high test-retest reliability. In a cohort of FRDA patients, the CKC levels were reduced by about 70% and correlated with the size of GAA1 triplet expansion and the age of symptoms onset suggesting that proprioceptive impairment in FRDA is genetically determined and scarcely progressive after symptoms onset. Here, the authors re-tested the same FRDA patients after 1 year to assess whether the CKC levels deteriorate over time or whether they remain stable as a sign of early developmental proprioceptive impairment.

Read the entire article HERE

Neurochemical profiles in hereditary ataxias: A meta-analysis of Magnetic Resonance Spectroscopy studies

Magnetic resonance spectroscopy (MRS) is applied to investigate the neurochemical profiles of degenerative hereditary ataxias. This meta-analysis provides a quantitative review and reappraisal of MRS findings in spinocerebellar ataxias (SCA) and Friedreich ataxia (FA) available to date. From each study, changes in N-acetyl aspartate (NAA), choline-containing compounds (Cho) and myo-Inositol (mI) ratios to total creatine (Cr) were calculated for groups of patients (1499 patients in total: SCA1 = 223, SCA2 = 298, SCA3 = 711, SCA6 = 165, and FA = 102) relative to their own control group, mostly in cerebellum and pons. SCA1, 2, 3, 6, and FA patients showed overall decreased NAA/Cr compared to controls. Decreased Cho/Cr was visible in SCA1, 2, and 3 and elevated mI/Cr in SCA2 patients in cerebellum. In SCA6 and FA Cho/Cr and mI/Cr did not differ with respect to controls but SCA6 patients indicated higher Cho/Cr compared to SCA1 patients in cerebellum. SCA2 subjects showed the lowest NAA/Cr and Cho/Cr in cerebellum and the highest mI/Cr compared to controls and other genotypes, and therefore the most promising results for a potential biomarker.

Read the entire article HERE

Page 11 of 186

SHARE

FacebookTwitterLinkedInYoutube
Event G.jpg

 

Archived in
  Scientific News


 

 

Tagged in
FARA Scientific News


Site Map     Privacy Policy     Service Terms     Log-in     Contact     Charity Navigator