Vesigen Therapeutics Awarded Grant from Friedreich’s Ataxia Research Alliance (FARA) to Develop a Targeted Genome Editing Therapeutic Strategy

March 14 2023. Vesigen Therapeutics, a biotechnology company developing targeted therapies by engineering a distinct class of human extracellular vesicles called ARMMs (ARrestin-domain 1 Mediated Microvesicles), is pleased to announce receipt of a FARA (Friedreich’s Ataxia Research Alliance) General Research Grant. Vesigen will evaluate its proprietary technology to deliver CRISPR-Cas genome editing complexes as a non-viral disease-modifying strategy for patients diagnosed with the neurodegenerative disease Friedreich’s Ataxia (FA).

Sensoren in der Kleidung plus KI: Erfolgversprechende Diagnosetechnologie: Bei Friedreich-Ataxie und Duchenne-Muskeldystrophie getestet

Patzer, K.-H. (2023). Sensoren in der Kleidung plus KI: Erfolgversprechende Diagnosetechnologie: Bei Friedreich-Ataxie und Duchenne-Muskeldystrophie getestet. MMW Fortschritte der Medizin, 165(S1), 46–46. doi:10.1007/s15006-023-2393-2

CRISPR/Cas9-based edition of frataxin gene in Dictyostelium discoideum for Friedreich’s Ataxia disease modeling

Gentili, H. G., Pignataro, M. F., Olmos, J., Pavan, M. F., Ibanez, L. I., Santos, J., & Velazquez, F. (2023). CRISPR/Cas9-based edition of frataxin gene in Dictyostelium discoideum for Friedreich’s Ataxia disease modeling. doi:10.1101/2023.02.27.530330

Here we present the development of a new model system for Friedreich's Ataxia (FA) using D. discoideum (Dd). FA is a rare disease caused by disfunction of frataxin (FXN), a protein involved in Fe-S cluster assembly machinery.

Reduced cerebello-cerebral functional connectivity correlates with disease severity and impaired white matter integrity in Friedreich ataxia

Kerestes, R., Cummins, H., Georgiou-Karistianis, N., Selvadurai, L. P., Corben, L. A., Delatycki, M. B., Egan, G. F., & Harding, I. H. (2023). Reduced cerebello-cerebral functional connectivity correlates with disease severity and impaired white matter integrity in Friedreich ataxia. Journal of neurology, 10.1007/s00415-023-11637-x. Advance online publication. https://doi.org/10.1007/s00415-023-11637-x

Compared to controls, people with FRDA showed significantly reduced connectivity between the anterior cerebellum and bilateral pre/postcentral gyri, and between the superior posterior cerebellum and left dorsolateral PFC. Greater disease severity correlated with lower connectivity in these circuits. Lower anterior cerebellum-motor cortex functional connectivity also correlated with slower speeded finger tapping and less fractional anisotropy in the superior cerebellar peduncles, internal capsule, and precentral white matter in the FRDA cohort. There were no significant between-group differences in inferior posterior cerebellar or dentate nucleus connectivity. This study indicates that altered cerebello-cerebral functional connectivity is associated with functional status and white matter damage in cerebellar efferent pathways in people with FRDA, particularly in motor circuits.

Proprioceptors-enriched neuronal cultures from induced pluripotent stem cells from Friedreich ataxia patients show altered transcriptomic and proteomic profiles, abnormal neurite extension, and impaired electrophysiological properties

Dionisi, C., Chazalon, M., Rai, M., Keime, C., Imbault, V., Communi, D., Puccio, H., Schiffmann, S. N., & Pandolfo, M. (2023). Proprioceptors-enriched neuronal cultures from induced pluripotent stem cells from Friedreich ataxia patients show altered transcriptomic and proteomic profiles, abnormal neurite extension, and impaired electrophysiological properties. Brain communications, 5(1), fcad007. https://doi.org/10.1093/braincomms/fcad007

The analysis of the transcriptomic and proteomic profile suggests an impairment of cytoskeleton organization at the growth cone, neurite extension and, at later stages of maturation, synaptic plasticity. Alterations in the spiking profile of tonic neurons are also observed at the electrophysiological analysis of mature neurons. Despite the reversal of the repressive epigenetic state at the FXN locus and the restoration of FXN expression, isogenic control neurons retain many features of Friedreich ataxia neurons. Our study suggests the existence of abnormalities affecting proprioceptors in Friedreich ataxia, particularly their ability to extend towards their targets and transmit proper synaptic signals. It also highlights the need for further investigations to better understand the mechanistic link between FXN silencing and proprioceptive degeneration in Friedreich ataxia.

FDA has approved Skyclarys (omaveloxolone) as the first treatment for Friedreich’s ataxia

 FDA approves first treatment for Friedreich’s ataxia

FDA Widens Path for Rare-Disease Treatments With New Approval

Reata Pharmaceuticals Announces FDA Approval of SKYCLARYS™ (Omavaloxolone), the First and Only Drug Indicated for Patients with Friedreich’s Ataxia

What is SKYCLARYS?

https://s27.q4cdn.com/486207181/files/doc_presentations/2023/20230228_RETA_Deck_SKYCLARYS_Approval_for_Patients_with_Friedreich%E2%80%99s_Ataxia.pdf

Strategic discussion on funding and access to therapies targeting rare diseases in Spain: an expert consensus paper

Zozaya, N., Villaseca, J., Abdalla, F., Ancochea, A., Málaga, I., Trapero-Bertran, M., … Hidalgo-Vega, A. (2023). Strategic discussion on funding and access to therapies targeting rare diseases in Spain: an expert consensus paper. Orphanet Journal of Rare Diseases, 18(1), 41. doi:10.1186/s13023-023-02635-3

The FINEERR project may provide a starting point for stakeholders involved in the process of funding and access to RD-targeted therapies to provide the necessary resources and implement measures to improve both the quality of life and life expectancy of patients with RDs. A coordinated effort is required from the different stakeholders, including the pharmaceutical industry, with clear leadership of healthcare authorities, to allow the overall healthcare system to meet the technical, political, economic, and social challenges ahead. Future studies should explore this issue further to assess how best to implement these recommendations over time.

Ataxia de friedreich, revisión bibliográfica

Investigación, R. S. (2023, febrero 22). Ataxia de friedreich, revisión bibliográfica. Recuperado el 23 de febrero de 2023, de ▷ RSI - Revista Sanitaria de Investigación website: https://revistasanitariadeinvestigacion.com/ataxia-de-friedreich-revision-bibliografica/ 

La ataxia de Friedreich es una enfermedad hereditaria y neurodegenerativa rara que afecta a personas jóvenes que se caracteriza por un deterioro lentamente progresivo de la coordinación en la marcha y en la capacidad para mantener correctamente la postura corporal, así como otros signos y síntomas neurológicos. Es la ataxia hereditaria más común con un patrón de herencia autosómica recesiva. La enfermedad causa en quienes la padecen un deterioro progresivo del cerebelo y ganglios espinales dorsales. Esta degeneración provoca en los afectados, de manera imparable, una pérdida progresiva de muchas de las funciones necesarias para una autonomía personal: pérdida de sensibilidad, descoordinación en los movimientos, escoliosis, disfagia, disartria, inmunodeficiencia, y predisposición al cáncer y en muchos casos diabetes y problemas cardíacos graves, causantes de la muerte en la mayoría de los casos. Los afectados por esta enfermedad, en un tiempo más o menos corto, acaban perdiendo toda autonomía personal.

Insights from yeast: Transcriptional reprogramming following metformin treatment is similar to that of deferiprone in a yeast Friedreich's ataxia model

Börklü E. Insights from yeast: Transcriptional reprogramming following metformin treatment is similar to that of deferiprone in a yeast Friedreich's ataxia model. Yeast (Chichester, England). 2023 Feb. DOI: 10.1002/yea.3845. PMID: 36755518. 

The comparative inquiry of transcriptome data reveals new promising roles for metformin in FRDA treatment since deferiprone and metformin treatments produce overlapping transcriptional and phenotypic responses in YFH1Δ cells. The results revealed that both deferiprone and metformin treatment does not rescue aerobic respiration in YFH1Δ cells, but they alleviate the FRDA phenotype probably by triggering the retrograde mitochondria-to-nucleus signaling.

Frataxin-deficient human brain microvascular endothelial cells lose polymerized actin and are paracellularly permeable -implications for blood-brain barrier integrity in Friedreich's Ataxia

Smith, F. M., & Kosman, D. J. (2023). Frataxin-deficient human brain microvascular endothelial cells lose polymerized actin and are paracellularly permeable -implications for blood-brain barrier integrity in Friedreich's Ataxia. bioRxiv : the preprint server for biology, 2023.02.09.527936. doi.org/10.1101/2023.02.09.527936 

We identified that insufficient FXN levels in the hBMVEC BBB model causes changes in cytoskeletal architecture and increased barrier permeability, cell pathologies that may be related to patient brain iron accumulation, neuroinflammation, neurodegeneration, and stroke. Our findings implicate other barrier cells, e.g., the cardiac microvasculature, likely contributory also to disease pathology in FRDA.