LEXEO Therapeutics Announces Upcoming Data Presentations at the American Society of Gene and Cell Therapy (ASGCT) 2021 Virtual Annual Meeting

NEW YORK, April 28, 2021 (GLOBE NEWSWIRE) -- LEXEO Therapeutics, a clinical-stage gene therapy company, today announced upcoming presentations regarding its investigational gene therapy programs at the American Society of Gene and Cell Therapy (ASGCT) 24th Annual Meeting, taking place virtually from May 11-14, 2021. he AAVrh.10 vector is currently being evaluated by LEXEO in pre-clinical studies for the treatment of cardiomyopathy associated with Friedreich’s ataxia (FA). Cardiomyopathy is the most common cause of mortality in patients with FA; it is the cause of death in nearly 70% of the patient population. 

LEXEO plans to initiate a Phase 1 clinical trial of LX2006 in patients with cardiomyopathy associated with FA and expects initial data from the Phase 1 trial of LX1001 in APOE4 associated Alzheimer’s disease in 2021.

Frataxin deficiency promotes endothelial senescence in pulmonary hypertension

Miranda K. Culley, Jingsi Zhao, Yi Yin Tai, Ying Tang, Dror Perk, Vinny Negi, Qiujun Yu, Chen-Shan C. Woodcock, Adam Handen, Gil Speyer, Seungchan Kim, Yen-Chun Lai, Taijyu Satoh, Annie M.M. Watson, Yassmin Al Aaraj, John Sembrat, Mauricio Rojas, Dmitry Goncharov, Elena A. Goncharova, Omar F. Khan, Daniel G. Anderson, James E. Dahlman, Aditi U. Gurkar,1 Robert Lafyatis, Ahmed U. Fayyaz, Margaret M. Redfield, Mark T. Gladwin, Marlene Rabinovitch, Mingxia Gu, Thomas Bertero, and Stephen Y. Chan; J Clin Invest. 2021. doi:10.1172/JCI136459. 

These findings also establish an endothelial etiology for PH in FRDA and left heart disease and support therapeutic development of senolytic drugs, reversing effects of Fe-S deficiency across PH subtypes.

AavantiBio and Catalent Announce Partnership to Support Development and Manufacturing of Gene Therapies for Rare Genetic Diseases

CAMBRIDGE, MASS. AND SOMERSET, N.J. (PRWEB) APRIL 27, 2021 

AavantiBio, a gene therapy company focused on transforming the lives of patients with rare genetic diseases, and Catalent, the leading global provider of advanced delivery technologies, development, and manufacturing solutions for drugs, biologics, cell and gene therapies, and consumer health products, today announced a partnership to support the development and manufacturing of AavantiBio’s gene therapies, including its lead program in Friedreich’s Ataxia (FA).

Longitudinal structural brain changes in Friedreich ataxia depend on disease severity: the IMAGE-FRDA study

Selvadurai LP, Georgiou-Karistianis N, Shishegar R, Sheridan C, Egan GF, Delatycki MB, Harding IH, Corben LA.; J Neurol (2021). https://doi.org/10.1007/s00415-021-10512-x 

Individuals with Friedreich ataxia had a greater rate of white matter volume loss than controls in the superior cerebellar peduncles and right peri-thalamic/posterior cerebral regions, and greater reduction in left primary motor cortex gyrification. Greater cerebellar/brainstem white matter volume loss and right dorsal premotor gyrification loss was observed amongst individuals with less severe neurological symptoms at Time 1. Conversely, cerebral atrophy and changes in axial diffusivity were observed in individuals with more severe Time 1 symptoms. Progression in radial diffusivity was more pronounced amongst individuals with earlier disease onset. Greater right ventral premotor gyrification loss correlated with greater neurological progression.

Remember friedreich ataxia even in a toddler with apparently isolated dilated (not hypertrophic!) cardiomyopathy: revisited

Anwar BABAN, Marianna CICENIA, Lorena TRAVAGLINI, Federica CALÍ, Gessica VASCO, Paola FRANCALANCI, Antonio NOVELLI, Rachele ADORISIO, Antonio AMODEO, Bruno DALLAPICCOLA, Enrico BERTINI, Fabrizio DRAGO. Minerva Pediatr 2021 Apr 02. DOI: 10.23736/S2724-5276.21.05969-3 

We believe on the importance of taking in consideration this rare condition even in a toddler with apparently isolated cardiomyopathy and especially when conventional investigations give negative results. We discuss potential trigger effect of heart transplant as a precipitating factor in manifesting neurological symptoms. This observation corresponds to our experience and relates to three patients described so far (the third patient died suddenly). Early onset cardiomyopathy with FRDA should increase awareness of this rare condition and we highlight HT successful outcome. Further reports are needed to delineate this rare condition in youngsters.

The Cardioprotective Mechanism of Phenylaminoethyl Selenides (PAESe) Against Doxorubicin-Induced Cardiotoxicity Involves Frataxin

Fu Xiaoyu, Eggert Mathew, Yoo Sieun, Patel Nikhil, Zhong Juming, Steinke Ian, Govindarajulu Manoj, Turumtay Emine Akyuz, Mouli Shravanthi, Panizzi Peter, Beyers Ronald, Denney Thomas, Arnold Robert, Amin Rajesh H.; Front. Pharmacol., 12 April 2021 doi:10.3389/fphar.2020.574656

Mechanistically, we demonstrated that DOX impedes the stability of the iron-sulfur cluster biogenesis protein Frataxin (FXN) (0.5 fold), resulting in enhanced mitochondrial free iron accumulation (2.5 fold) and reduced aconitase activity (0.4 fold). Our findings further indicate that PAESe prevented the reduction of FXN levels and the ensuing elevation of mitochondrial free iron levels.

Diseases Costs and Impact of the Caring Role on Informal Carers of Children with Neuromuscular Disease

Rodríguez, A.A.; Martínez, Ó.; Amayra, I.; López-Paz, J.F.; Al-Rashaida, M.; Lázaro, E.; Caballero, P.; Pérez, M.; Berrocoso, S.; García, M.; Luna, P.M.; Pérez-Núñez, P.; Passi, N.. International Journal of Environmental Research and Public Health. 2021 Mar;18(6). DOI: 10.3390/ijerph18062991. 

This study shows that carers of children with NMDs have to face a number of high costs related to their own physical and psychological health. Women represented the majority percentage of participants, and most of them had severely dependent children. Therefore, it was perceived that both the group of children with severe support needs, as well as their carers, had greater needs. In turn, it is important to note that there is some public funding for those affected to ensure that they can have access to health services. However, funding from regional governments and non-profit organizations is virtually non-existent for expenses associated with professional support for carers. Moreover, if these carers start from a low socioeconomic situation, dedicating themselves to caregiving increases their vulnerability. Therefore, these situations give rise to social inequality in this group. Finally, our study also found that carers who are female, single or separated and unemployed showed worse physical and psychological health.

A Phase 2a investigator-initiated open-label clinical trial assessing elamipretide

BOSTON, April 6, 2021 /PRNewswire/ -- Stealth BioTherapeutics Corp (Nasdaq: MITO), a clinical-stage biotechnology company focused on the discovery, development, and commercialization of novel therapies for diseases involving mitochondrial dysfunction, today reported financial results for the year ended December 31, 2020 and announced recent business highlights. 

Expansion of cardiomyopathy franchise: A Phase 2a investigator-initiated open-label clinical trial assessing elamipretide in a cohort of patients affected by visual decline and/or cardiomyopathy associated with Friedreich's ataxia is expected to commence during Q2 2021.

Healx launches partnership with Ataxia UK and FARA to find treatments for rare neurodegenerative condition

Cambridge UK – 7 April 2021 – Healx, the AI-powered, patient-inspired technology company accelerating the discovery and development of rare disease treatments at scale, is excited to announce its latest patient group partnerships. Working in collaboration with Ataxia UK and FARA, Healx will leverage its state-of-the-art AI platform and drug discovery expertise to develop novel treatments for Friedreich’s ataxia – a rare neurodegenerative condition that causes issues with balance, speech and coordination.

Biochemical alterations precede neurobehavioral deficits in a novel mouse model of Friedreich ataxia

Marta Medina-Carbonero, Arabela Sanz-Alcazar, Elena Britti, Fabien Delaspre, Elisa Cabiscol, Joaquim Ros, Jordi Tamarit; bioRxiv 2021.04.05.438486; doi: doi:10.1101/2021.04.05.438486 

In the present work, we have characterized a new mouse model of FA (FXNI151F) based on a pathological point mutation (I154F) present in some FA patients. These mice present very low frataxin levels in all tissues and display neurological deficits resembling those observed in FA patients. We have also observed decreased content of components from OXPHOS complexes I and II, decreased aconitase activity, and alterations in the antioxidant defenses. Remarkably, these biochemical alterations precede the appearance of neurological symptoms and present a different profile in heart and brain or cerebellum. The FXNI151F mouse is an excellent tool for analyzing the consequences of frataxin deficiency in different tissues and for testing new therapies.

Synthesis of 5‐[(1H‐indol‐3‐yl)methyl]‐1,3,4‐oxadiazole‐2(3H)‐thiones and their protective activity against oxidative stress

škauskienė, M., Kadlecová, A., Voller, J., Janovská, L., Malinauskienė, V., Žukauskaitė, A., Šačkus, A., Arch. Pharm. 2021, e2100001. doi:10.1002/ardp.202100001

A series of 5‐[(1H‐indol‐3‐yl)methyl]‐1,3,4‐oxadiazole‐2(3H)‐thiones was synthesized in this study. Methyl substitution on the indole ring and propyl, butyl, or benzyl substitution on sulfhydryl group‐possessing compounds were revealed to protect Friedreich's ataxia fibroblasts against chemically induced oxidative stress. Two of the active compounds also reproducibly increased the survival of Caenorhabditis elegans exposed to juglone‐induced oxidative stress.