S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases

Vrettou S, Wirth B.; International Journal of Molecular Sciences. 2022 Dec;23(24):15849. DOI: 10.3390/ijms232415849. PMID: 36555492; PMCID: PMC9779533. 

We discuss how S-glutathionylation and S-nitrosylation interfere in mitochondrial homeostasis and how the deregulation of these modifications is associated with Alzheimer's, Parkinson's, amyotrophic lateral sclerosis and Friedreich's ataxia.

ODs with a positive TPR conclusion, not subject to a conditional approval, and approved without requering a pass would be more likely to be reimbursed in Spain

José Luis Poveda, Claudia Gómez, Alicia Gil & Xavier Badia; Orphanet J Rare Dis 18, 4 (2023). doi:10.1186/s13023-022-02610-4 

This study shows that the TPR plays a key role in the P&R process in Spain and highlights that traditional evaluation tools, such us safety and efficacy, were the main drivers of P&R decisions for ODs. A positive conclusion of the TPR, non-conditional approval by the EMA and no obligation for a PASS seems to favourably affect P&R decisions in Spain.

Open Innovation for an Inclusive Labor Market for University Students with Disabilities

Espada-Chavarria, R.; Diaz-Vega, M.; González-Montesino, R.H.; J. Open Innov. Technol. Mark. Complex. 2021, 7, 217. doi:10.3390/joitmc7040217 

 This descriptive and quantitative study discusses the results obtained after implementing an open innovation program to promote access to internships for university students with disabilities, in which three multi-national companies have participated. We used the Job Typicalness, Quality of Work Life and Employment Maturity Interview Questionnaires to collect information. The results show that the jobs performed by disabled participants are similar to those of other workers. This job typicality positively influences their perception of quality of life and job satisfaction. The open innovation process has focused on collaboration to provide accessibility and equity to the procedures of human resources departments for access to employment, that is, external collaboration has been used to offer an equal-opportunity hiring process. The information obtained allows us to conclude that companies need to increase their training and/or knowledge in the fields of diversity and inclusion to eliminate the barriers of access to employment found in hiring processes. This study reveals the importance of this type of open innovation among companies and organizations, not only for establishing diversity-sensitive human resources policies, but also for promoting the talent attraction with equal opportunities and an inclusive labour market.

Iron-frataxin involved in the protective effect of quercetin against alcohol-induced liver mitochondrial dysfunction

Liu J, Chen H, Lin H, Peng S, Chen L, Cheng X, Yao P, Tang Y.; J Nutr Biochem. 2022 Dec 29:109258. doi: 10.1016/j.jnutbio.2022.109258. Epub ahead of print. PMID: 36587874. 

 Frataxin deficiency reduced the protective effects of quercetin on mitochondria disordered by ethanol.

Drosophila melanogaster frataxin: protein crystal and predicted solution structure with identification of the iron-binding regions

Rodrigues AV, Batelu S, Hinton TV, Rotondo J, Thompson L, Brunzelle JS, Stemmler TL.; Acta Crystallogr D Struct Biol. 2023 Jan 1;79(Pt 1):22-30. doi: 10.1107/S2059798322011639. Epub 2023 Jan 1. PMID: 36601804. 

 The goal of this report is to provide structural details of the Drosophila melanogaster frataxin ortholog (Dfh), using both X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, in order to provide the foundational insight needed to understand the structure-function correlation of the protein.

Histopathology of the cerebellar cortex in essential tremor and other neurodegenerative motor disorders: comparative analysis of 320 brains

Elan D. Louis, Regina T. Martuscello, John T. Gionco, Whitney G. Hartstone, Jessica B. Musacchio, Marisa Portenti, Morgan McCreary, Sheng-Han Kuo, Jean-Paul G. Vonsattel & Phyllis L. Faust; Acta Neuropathol (2023). doi:10.1007/s00401-022-02535-z 

We conducted comparative analyses in a postmortem series of 320 brains on the severity and patterning of cerebellar cortex degenerative changes in ET (n = 100), other neurodegenerative disorders of the cerebellum [spinocerebellar ataxias (SCAs, n = 47, including 13 SCA3 and 34 SCA1, 2, 6, 7, 8, 14); Friedreich’s ataxia (FA, n = 13); multiple system atrophy (MSA), n = 29], and other disorders that may involve the cerebellum [Parkinson’s disease (PD), n = 62; dystonia, n = 19] versus controls (n = 50).

Mitochondrial Calcium Homeostasis in the Pathology and Therapeutic Application in Friedreich's Ataxia

Hongting Zhao, Zhuoyuan Li, Yutong Liu, Meng Zhang & Kuanyu Li. Neurosci. Bull. (2022). doi:10.1007/s12264-022-01007-4

Gambling associated risk-taking decision in cerebellar ataxia

Ruo-Yah Lai Natasha A. Desai Christian J. Amlang Chi-Ying R. Lin Tiffany X. Chen Michael J. Minyetty Nadia Amokrane Sheng-Han Kuo;  Parkinsonism & Related Disorders, Volume 0, Issue 0, 105252,  doi:10.1016/j.parkreldis.2022.105252 

People with cerebellar ataxia (CA) can develop impulsive and compulsive behaviors that significantly affect their and their family's quality of life. To further assess the decision-making process associated with these behaviors, we used the Iowa Gambling Task (IGT) to study people with CA.

CA cases obtained significantly lower IGT total scores than controls (−5.30 ± 37.53 vs. 21.30 ± 37.37, p = 0.004). In addition, those with CA made riskier decisions throughout the task compared to controls. Although both CA and controls learned to make decisions with more favorable outcomes over the course of completing the IGT, CA participants never matched the controls' performance. IGT performance did not correlate with ataxia severity or depressive symptoms.

SHAREHOLDER ALERT: Pomerantz Law Firm Investigates Claims On Behalf of Investors of Design Therapeutics, Inc.

NEW YORK, Dec. 26, 2022 /PRNewswire/ -- Pomerantz LLP is investigating claims on behalf of investors of Design Therapeutics, Inc. ("Design" or the "Company") (NASDAQ: DSGN). 

On or around March 24, 2021, Design conducted its initial public offering ("IPO"), selling 12 million shares of stock priced at $20.00 per share. Then, on December 7, 2022, Design reported initial data from a Phase 1 trial of DT-216 in patients with Friedreich ataxia. Among other results, Design said 16 patients on DT-216 and eight on placebo reported at least one treatment-emergent adverse event. On this news, Design's stock price fell sharply during intraday trading on December 8, 2022.

The psychosocial situation of families caring for children with rare diseases during the COVID-19 pandemic: results of a cross-sectional online survey

Lydia Rihm, Mareike Dreier, Farhad Rezvani, Silke Wiegand-Grefe & Jörg Dirmaier; Orphanet J Rare Dis 17, 449 (2022). doi:10.1186/s13023-022-02595-0 

 This study indicates a high psychosocial burden on family caregivers of children with RDs during the early COVID-19 pandemic, characterized by high distress levels and wide-ranging everyday problems, unmet psychosocial information needs, and reduced caregiver-reported HRQoL in children with RDs. The findings highlight the ongoing need for target group-specific, low-threshold support services (e.g., websites) during and after the pandemic.