Neurologic orphan diseases: Emerging innovations and role for genetic treatments

Kioutchoukova IP, Foster DT, Thakkar RN, Foreman MA, Burgess BJ, Toms RM, Molina Valero EE, Lucke-Wold B. Neurologic orphan diseases: Emerging innovations and role for genetic treatments. World J Exp Med 2023; 13(4): 59-74  doi: 10.5493/wjem.v13.i4.59

 Emerging innovations and the role of genetic treatments open a new window of opportunity for the treatment of neurologic orphan diseases.

Benefits of Adaptive Sport on Physical and Mental Quality of Life in People with Physical Disabilities: A Meta-Analysis

Isidoro-Cabañas E, Soto-Rodríguez F, Morales-Rodríguez F, Pérez-Mármol J. Benefits of Adaptive Sport on Physical and Mental Quality of Life in People with Physical Disabilities: A Meta-Analysis; Healthcare (Basel, Switzerland). 2023 Sep;11(18). PMCID: PMC10531072. doi:10.3390/healthcare11182480 

The engagement in adaptive sports showed a positive impact on the mental quality of life among adults with physical disabilities. However, the positive effect of adaptive sports practice on physical quality of life was shown only in the pre–post-test analysis. Further studies are required to validate the obtained findings.

Comparison of Live and Remote Video Ratings of the Scale for Assessment and Rating of Ataxia

Taheri Amin A, Faber J, Önder D, et al. Comparison of Live and Remote Video Ratings of the Scale for Assessment and Rating of Ataxia; Movement Disorders Clinical Practice. 2023 Aug;10(9):1404-1407. PMCID: PMC10525045. DOI: 10.1002/mdc3.13843 

Live and remote video ratings showed a high level of agreement for the complete score (bias = 0.09, with standard deviation = 2.00) and all single SARA items (bias<0.20 for all items).

Conclusion: Remote video ratings of SARA are a reliable means to assess severity of ataxia.

Pre-Validation of a Virtual Reality Tool to Quantify the Severity of Friedreich's Ataxia

K. Chenier, A. Duquette, L. Touma, M. T. Le and D. R. Labbe, "Pre-Validation of a Virtual Reality Tool to Quantify the Severity of Friedreich's Ataxia," 2023 IEEE 11th International Conference on Serious Games and Applications for Health (SeGAH), Athens, Greece, 2023, pp. 1-7, doi: 10.1109/SeGAH57547.2023.10253802.

 The results of this study demonstrate the feasibility of using VR with FA patients, although adaptation of the technology may be necessary for those with more severe impairments.

CRISPR/Cas9-Based Edition of Frataxin Gene in Dictyostelium discoideum

Hernan Gustavo Gentili, María Florencia Pignataro, Justo Facundo Olmos, María Florencia Paván, Lorena Itatí Ibáñez, Javier Santos, Francisco Velazquez Duarte; CRISPR/Cas9-Based Edition of Frataxin Gene in Dictyostelium discoideum. Biochem J 2023; BCJ20230244. doi:10.1042/BCJ20230244 

The results of the study suggest that this new D. discoideum strain offers a wide range of possibilities to easily explore diverse FA FXN variants. This can facilitate the development of straightforward drug screenings to look for new therapeutic strategies.

Long non-coding RNA TUG1 is down-regulated in Friedreich's ataxia

Long non-coding RNA TUG1 is down-regulated in Friedreich's ataxia. Mert Koka, Hui Li, Rumana Akther, Susan Perlman, Darice Wong, Brent L Fogel, David R Lynch, Vijayendran Chandran, bioRxiv 2023.09.22.558879; doi: 10.1101/2023.09.22.558879 

This suggests that elevated TUG1 levels correlate with earlier onset and more severe cases. In summary, this study highlights Tug1 as a crucial blood-based biomarker for FRDA. Tug1's consistent expression variance across human and mouse tissues is closely associated to disease severity and key FRDA pathways. It also correlates strongly with Fxn levels, making it a promising early, non-invasive marker. TUG1 offers potential for FRDA monitoring and therapeutic development, warranting further clinical research.

Innovative thinking of clinical investigation for rare disease drug development

Wang, P., Chow, SC. Innovative thinking of clinical investigation for rare disease drug development. Orphanet J Rare Dis 18, 299 (2023). doi:10.1186/s13023-023-02909-w 

Many clinical trials for drug development are powered on effectiveness only, and safety issue is considered as the secondary objective. This practice has made some approved drugs have safety concerns, and some are even withdrawn or recalled. One possible reason for researchers not power on safety is that testing for safety requires a much larger sample size. As for orphan drug development, this problem is even worse due to the limited availability of participants.

Periodontal Treatment of Norwegian Patients With Rare Diseases: A Commentary

Øystein Fardal, Irene Skau, Jostein Grytten, Periodontal Treatment of Norwegian Patients With Rare Diseases: A Commentary, International Dental Journal, 2023, doi:10.1016/j.identj.2023.07.009. 

 An autosomal recessive disease that causes neurodegeneration. It results in muscle weakness and loss of sensation and proprioception, causing problems with movement as well as impaired speech. The symptoms tend to worsen as time progresses, so many patients end up in wheelchairs, lose their vision and hearing, and experience other medical complications such as diabetes mellitus and scoliosis. The cause of the disease is a reduction in frataxin, which is necessary for the production of mitochondrial adenosine triphosphate (ATP) and the management of iron stores. No previous connections with periodontal complications have been reported; however, diabetes is a known risk factor. In addition, the inability to perform adequate oral hygiene due to the disability may be an important risk factor.

Analytical Method and Stability Study for Oral Suspension of Idebenone in Syrspend

Porru, E.; Piro, F.; Comito, R.; Mosendz, A.; Minniti, E.; Conti, M.; Stancari, A.; Violante, F.S. Analytical Method and Stability Study for Oral Suspension of Idebenone in Syrspend. Separations 2023, 10, 517. doi:10.3390/separations10090517 

The greatest disadvantage of IDB is its low solubility in water, resulting in low bioavailability. Galenic preparations of IDB in customized doses are common for pediatric patients, which can often prove to be the only option for access to therapy. As an antioxidant, the chemical stability of IDB is an essential guarantee for exerting the desired antioxidant action. Stability studies are essential to know the effect of storage conditions of a galenic product. For the first time, a stability-indicating LC-MS method has been developed to define the stability of IDB suspensions in SyrSpend® Sugar-Free Unflavored (Fagron), a carrier phase formulated for setting up suspensions of active pharmaceutical ingredients (APIs) insoluble or poorly insoluble in water and compatible with it.

Patient-derived iPSC models of Friedreich ataxia: a new frontier for understanding disease mechanisms and therapeutic application

Maheshwari S, Vilema-Enríquez G, Wade-Martins R. Patient-derived iPSC models of Friedreich ataxia: a new frontier for understanding disease mechanisms and therapeutic application. Transl Neurodegener. 2023 Sep 20;12(1):45. doi: 10.1186/s40035-023-00376-8. PMID: 37726850. 

These models enable studies of the molecular mechanisms underlying GAA-induced pathology, as well as providing an exciting tool for the screening and testing of novel disease-modifying therapies. This review explores how the use of iPSCs to study FRDA has developed over the past decade, as well as discussing the enormous therapeutic potentials of iPSC-derived models, their current limitations and their future direction within the field of FRDA research.