Accept Cookies?
Provided by OpenGlobal E-commerce

Please wait while your page loads ...

 

FARA Funded Research

Your generous support has funded all the research listed below.


For more information on FARA-funded research & scientists, please visit FARA Supported Research, Active Clinical Trials and the Featured Scientist.

Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia

In this study, the authors examined the metabolic, neuroprotective and frataxin-inducing effects of glucagon-like-peptide 1 (GLP-1) analogs in in vivo and in vitro models and in Friedreich ataxia patients. The GLP-1 analog exenatide improved glucose homeostasis of frataxin-deficient mice through enhanced insulin content and secretion in pancreatic β-cells. Exenatide induced frataxin and iron-sulfur cluster-containing proteins in β-cells and brain, and was protective to sensory neurons in dorsal root ganglia. GLP-1 analogs also induced frataxin expression, reduced oxidative stress and improved mitochondrial function in Friedreich ataxia patients' induced pluripotent stem cell-derived β-cells and sensory neurons. The frataxin-inducing effect of exenatide was confirmed in a pilot trial in Friedreich ataxia patients, showing modest frataxin induction in platelets over a 5-week treatment course. Taken together, GLP-1 analogs improve mitochondrial function in frataxin-deficient cells and induce frataxin expression. These findings identify incretin receptors as a therapeutic target in Friedreich 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

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

Mitochondrial dysfunction in neurons in Friedreich's ataxia

Based on clinical evidence, the peripheral nervous system is affected early in Friedreich's ataxia, neuronal dysfunction progresses towards the central nervous system, and other organs (such as heart and pancreas) are affected later. However, little attention has been given to the specific aspects of mitochondria function altered by frataxin depletion in the nervous system. For years, commonly accepted views on mitochondria dysfunction in Friedreich's ataxia stemmed from studies using non-neuronal systems and may not apply to neurons, which have their own bioenergetic needs and present a unique, extensive neurite network. Moreover, the basis of the selective neuronal vulnerability, which primarily affects large sensory neurons in the dorsal root ganglia, large principal neurons in the dentate nuclei of the cerebellum, and pyramidal neurons in the cerebral cortex, remains elusive. In order to identify potential misbeliefs in the field and highlight controversies, the authors reviewed current knowledge on frataxin expression in different tissues, discussed the molecular function of frataxin, and the consequences of its deficiency for mitochondria structural and functional properties, with a focus on the nervous system.

Read the entire article HERE

Orphan Drugs In Development For The Treatment Of Friedreich's Ataxia: Focus On Omaveloxolone

Nrf2 activators such as omaveloxolone (Omav) modulate antioxidative mechanisms, and thus may be viable therapeutic agents in Friedreich's Ataxia (FRDA). This paper reviews the MOXIe trial (NCT02255435, Reata Pharmaceuticals Inc) and the use of other Nrf2 activators as a viable option in the treatment of FRDA.

Read the entire article HERE

Page 5 of 33

SHARE

FacebookTwitterLinkedInYoutube
Event D.jpg

 

Archived in
  Scientific News


 

 

Tagged in
FARA Scientific News


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