Altered calcium responses and antioxidant properties in Friedreich’s ataxia-like cerebellar astrocytes

Altered calcium responses and antioxidant properties in Friedreich’s ataxia-like cerebellar astrocytes Chiara Marullo, Laura Croci, Iris Giupponi, Claudia Rivoletti, Sofia Zuffetti, Barbara Bettegazzi, Filippo Casoni, Ottavio Cremona, Gian Giacomo Consalez, Franca Codazzi bioRxiv 2024.07.19.604129; doi: 10.1101/2024.07.19.604129 

Our findings shed light on cellular changes caused by FXN downregulation in cerebellar astrocytes, which can interfere with their physiological and complex interaction with neurons. The potentially impaired ability to provide neuronal cells with glutathione or to release neuromodulators and bioactive molecules in a calcium-dependent manner could impact neuronal function and contribute to neurodegeneration.

Relative Bioavailability of Omaveloxolone When Capsules Are Sprinkled Over and Mixed in Applesauce Compared With Administration as Intact Omaveloxolone Capsules: A Phase 1, Randomized, Open-Label, Single-Dose, Crossover Study in Healthy Adults

Hynes SM, Goldsberry A, Henneghan PD, et al. Relative bioavailability of omaveloxolone when capsules are sprinkled over and mixed in applesauce compared with administration as intact omaveloxolone capsules: A phase 1, randomized, open-label, single-dose, crossover study in healthy adults. J Clin Pharm. 2024;: 00-00. doi:10.1002/jcph.2482 

Some patients with FA may have oropharyngeal dysphagia or difficulty swallowing whole capsules; therefore, alternate method(s) of administration are needed. A Phase 1 clinical study in 32 healthy volunteers evaluated the relative bioavailability, safety, and tolerability of a single dose of omaveloxolone when capsule contents were sprinkled on and mixed in applesauce compared to when taken as intact capsules. Palatability when sprinkled on and mixed in applesauce was assessed with a questionnaire.

Advancing Understanding of Predictive Factors for Survival in Friedreich's Ataxia: A Review of Current Evidence and Future Directions

Xia F, Su C. Advancing Understanding of Predictive Factors for Survival in Friedreich's Ataxia: A Review of Current Evidence and Future Directions. Mov Disord. 2024 Jun;39(6):1081-1082. doi: 10.1002/mds.29869. PMID: 38923013.

Indelicato E, Boesch S. Reply to: "Advancing Understanding of Predictive Factors for Survival in Friedreich's Ataxia: A Review of Current Evidence and Future Directions". Mov Disord. 2024 Jun;39(6):1082. doi: 10.1002/mds.29873. PMID: 38924164.   

C-Path partners with FARA to fortify RDCA-DAP and further accelerate drug development with new Friedreich’s Ataxia Data

TUCSON, Ariz., June 18, 2024 — Critical Path Institute (C-Path), a leader in accelerating drug development for rare diseases, today announced the targeted integration of additional Friedreich’s ataxia (FA) datasets into C-Path’s Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP®) as part of a partnership with Friedreich’s Ataxia Research Alliance (FARA). 

“RDCA-DAP’s extensive resources can amplify the impact of the existing data and foster new discoveries in FA research. This collaboration will build upon our strong, sustained, and productive partnership with the C-Path team,” said Farmer.

Friedreich’s Ataxia and Cesarean Delivery: A Case Report of Epidural Anesthesia With Ropivacaine

Theodosopoulou P, Mavromati M, Paraskeva A (June 06, 2024) Friedreich’s Ataxia and Cesarean Delivery: A Case Report of Epidural Anesthesia With Ropivacaine. Cureus 16(6): e61776. doi:10.7759/cureus.61776 

Overall management and the choice to proceed with neuraxial anesthesia in a woman with FRDA should be based on comprehensive consultations in both cardio-obstetrics and pre-anesthetic evaluations.

Microfluidic Formulation of Diazoxide-Loaded Solid Lipid Nanoparticles as a Novel Approach for Friedreich's Ataxia Treatment

Ilaria Arduino, Antonella Santoro, Silvia De Santis, Rosa Maria Iacobazzi, Angela Assunta Lopedota, Eleonora Paradies, Giuseppe Merla, Sara Anjomani Virmouni, Luigi Palmieri, Carlo Marya Thomas Marobbio, Nunzio Denora, Microfluidic Formulation of Diazoxide-Loaded Solid Lipid Nanoparticles as a Novel Approach for Friedreich's Ataxia Treatment, Journal of Drug Delivery Science and Technology, 2024, 105837, ISSN 1773-2247, doi: 10.1016/j.jddst.2024.105837. 

 These findings suggest SLN-DZX as a potential therapeutic approach for FRDA, mitigating oxidative stress with improved BBB penetration and reduced toxicity.

The Mechanism of Folding of Human Frataxin in Comparison to the Yeast Homologue - Broad Energy Barriers and the General Properties of the Transition State

Pietrangeli P, Marcocci L, Pennacchietti V, Diop A, Di Felice M, Pagano L, Malagrinò F, Toto A, Brunori M, Gianni S. The Mechanism of Folding of Human Frataxin in Comparison to the Yeast Homologue - Broad Energy Barriers and the General Properties of the Transition State. J Mol Biol. 2024 May 15;436(10):168555. doi: 10.1016/j.jmb.2024.168555. Epub 2024 Mar 27. PMID: 38552947. 

 We compared results from yeast and human frataxin providing insights into the impact of native topology on the folding mechanism and elucidating the properties of the underlying free energy landscape. The findings are discussed in the context of the funneled energy landscape theory of protein folding.

The genetic basis of early-onset hereditary ataxia in Iran: results of a national registry of a heterogeneous population

Mahdieh N, Heidari M, Rezaei Z, et al. The genetic basis of early-onset hereditary ataxia in Iran: results of a national registry of a heterogeneous population. Human Genomics. 2024 Apr;18(1):35. DOI: 10.1186/s40246-024-00598-5. PMID: 38570878; PMCID: PMC10988936.

 Friedreich ataxia (FA), ataxia telangiectasia (AT), ataxia with oculomotor apraxia (AOA), and autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) are among the most common forms of ARCA. These conditions typically present with a complicated phenotype. For instance, FA, the most prevalent recessive ataxia affecting 1 in 50,000 individuals in white populations, is caused by homozygous expansions of an intronic GAA trinucleotide repeat in the FXN gene

Mitochondrial calcium regulation of cardiac metabolism in health and disease

Balderas E, Lee SH, Rai NK, et al. Mitochondrial calcium regulation of cardiac metabolism in health and disease. Physiology (Bethesda, Md.). 2024 May. DOI: 10.1152/physiol.00014.2024. PMID: 38713090. 

In this review, we delve into recent insights further defining the relationship between mitochondrial Ca2+ dynamics and oxidative phosphorylation. Our focus is on how such regulation affects cardiac function in health and disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, mitochondrial cardiomyopathies, Barth syndrome, and Friedreich's ataxia.

Revisiting Friedreich's Ataxia: Phenotypic and Imaging Characteristics

Mahale R, Purushottam M, Singh R, Yelamanchi R, Kamble N, Holla V, Pal PK, Jain S, Yadav R. Revisiting Friedreich's Ataxia: Phenotypic and Imaging Characteristics. Ann Indian Acad Neurol. 2024 Mar-Apr;27(2):152-157. doi: 10.4103/aian.aian_1001_23. Epub 2024 Apr 12. PMID: 38751907; PMCID: PMC11093178.

A retrospective cross-sectional, descriptive analysis of genetically proven FRDA patients was performed. A detailed review of all the hospital case records was done to analyze the clinical, radiologic, and electrophysiologic details.