The Role of Voltage-Dependent Anion Channel in Mitochondrial Dysfunction and Human Disease

Varughese J, Buchanan S, Pitt A., Cells. 2021 Jul;10(7). PMCID: PMC8305817 doi:10.3390/cells10071737

The voltage-dependent anion channel (VDAC) is a β-barrel membrane protein located in the outer mitochondrial membrane (OMM). VDAC has two conductance states: an open anion selective state, and a closed and slightly cation-selective state. VDAC conductance states play major roles in regulating permeability of ATP/ADP, regulation of calcium homeostasis, calcium flux within ER-mitochondria contact sites, and apoptotic signaling events. Three reported structures of VDAC provide information on the VDAC open state via X-ray crystallography and nuclear magnetic resonance (NMR). Together, these structures provide insight on how VDAC aids metabolite transport. The interaction partners of VDAC, together with the permeability of the pore, affect the molecular pathology of diseases including Parkinson’s disease (PD), Friedreich’s ataxia (FA), lupus, and cancer.

Determining the Validity of Conducting Rating Scales in Friedreich Ataxia through Video

Tai, G., Corben, L.A., Woodcock, I.R., Yiu, E.M. and Delatycki, M.B. (2021); Mov Disord Clin Pract, 8: 688-693. doi:10.1002/mdc3.13204 

Excellent test–retest reliability was demonstrated in the majority of the mFARS sections, and in the total mFARS and SARA scores, suggesting that video is a valid method of conducting these scales. This method enables inclusion of participants who are unable to travel to study sites. A larger cohort will be required to further validate the use of video mFARS and SARA for future studies.

Polyuria and Acute Hyperglycemia Secondary to New-Onset Diabetes in a Young Woman With Friedreich’s Ataxia

Santos J, Woloski J R, Wu N (June 29, 2021); Cureus 13(6): e16032. doi:10.7759/cureus.16032 

Diabetes is a common complication in patients with FRDA and should be routinely screened for by healthcare providers, preferably via an OGTT. Treatment of diabetes can be challenging due to neurodegenerative symptoms that may interfere with the ability to self-administer insulin. Additionally, close follow-up with cardiology is important to monitor for any signs or symptoms of cardiomyopathy, especially after the initiation of diabetes medications. Once diabetes is diagnosed, an individualized treatment plan along with efficient coordination of care is essential for successful diabetes management in patients with FRDA.

Cardiac Involvement in Movement Disorders

Rossi M, Wainsztein N, Merello M.; Mov Disord Clin Pract. 2021 Apr 7;8(5):651-668. doi: 10.1002/mdc3.13188. PMID: 34307738; PMCID: PMC8287161.

As cardiac disease is part of the phenotypic spectrum of several movement disorders, heart involvement should be carefully investigated and increased awareness of this association encouraged as it may represent a leading cause of morbidity and mortality.

Neuro-Ophthalmological Findings in Friedreich’s Ataxia

Rojas, P.; de Hoz, R.; Cadena, M.; Salobrar-García, E.; Fernández-Albarral, J.A.; López-Cuenca, I.; Elvira-Hurtado, L.; Urcelay-Segura, J.L.; Salazar, J.J.; Ramírez, J.M.; Ramírez, A.I.; J. Pers. Med. 2021, 11, 708. doi:10.3390/jpm11080708 

Although most patients with FRDA do not present with symptomatic visual impairment, 73% present with clinical neuro-ophthalmological alterations such as optic atrophy and altered eye movement, among others. This review provides a brief overview of the main aspects of FRDA and then focuses on the ocular involvement of this pathology and the possible use of retinal biomarkers.

Very late-onset Friedreich’s ataxia with rapid course mimicking as possible multiple system atrophy cerebellar type

Tushar Ashok Vidhale, Hemant R Gupta, Rohan PJ and Charmi Gandhi; BMJ Case Reports CP 2021;14:e242073, doi:10.1136/bcr-2021-242073 

This 55-year-old man was admitted to the hospital with an insidious onset, progressive backward fall (due to severe truncal ataxia), dysarthria, stiffness in extremities, distal dominant muscle wasting along with behavioural changes and urinary incontinence. Clinical assessment indicated mild cognitive decline (Mini-Mental State Examination 22/27) with cerebellar, pyramidal and peripheral nerves involvement. On investigations, nerve conduction studies revealed symmetrical, sensorimotor peripheral neuropathy affecting both lower limbs. Brain and whole spine MRI revealed widespread cerebral and mild cerebellar atrophy, pons and medulla volume loss, and a normal spinal cord. Transthoracic echocardiography revealed concentric left ventricular hypertrophy. His gene analysis revealed eight GAA repeats on allele 1, and 37 GAA repeats on allele 2 in the first intron of the frataxin gene. Considering his clinical profile and genetic analysis, he was diagnosed as a case of very late-onset Friedreich’s ataxia with likely compound heterozygous genotype.

A Study to Assess Efficacy, Long Term Safety and Tolerability of RT001 in Subjects With Friedreich's Ataxia

UCLA Health, NCT No. NCT04102501; Phase 3 

 The purpose of this study is to assess the Efficacy, Long Term Safety and Tolerability of RT001 in subjects with Friedreich's Ataxia 

 Open Actively Recruiting

Rare occurrence of severe blindness and deafness in Friedreich ataxia: a case report

Joana Damásio, Ana Sardoeira, Maria Araújo, Isabel Carvalho, Jorge Sequeiros & José Barros; Cerebellum & Ataxias volume 8, Article number: 17 (2021) doi:10.1186/s40673-021-00140-6 

With this report we wish to further contribute to the characterization of optic and auditory involvement in FRDA, stress the need to better understand the underlying mechanisms, as well as their genetic and epigenetic modifying factors (including somatic heterogeneity); and increase awareness for this rare extreme phenotype. Improved healthcare services and longer survival of early-onset patients will probably increase the frequency of these devastating manifestations.

Gene therapies and COVID-19 vaccines: a necessary discussion in relation with viral vector-based approaches

Angel Aledo-Serrano, Antonio Gil-Nagel, Julian Isla, Ana Mingorance, Fernando Mendez-Hermida & Ruben Hernandez-Alcoceba; Orphanet J Rare Dis 16, 316 (2021). doi:10.1186/s13023-021-01958-3 

 In conclusion, the potential interference between gene therapy and virus-based vaccines deserves a careful consideration and discussion involving the patient community. This is a adequate moment to do so, since current vaccine candidates are not expected to cause such interference. Should people with monogenic diseases preferentially receive, or be given the option to be immunized COVID-19 vaccines based on non-viral platforms, such as the mRNA vaccines? A careful consideration of the impact on the use of vectors for vaccine production and the plausible negative impact in the development of suitable gene therapy medicinal products, should be on top of the scientific and regulatory table discussion in order to facilitate access to patients suffering monogenic diseases and also prevent unnecessary delays in future vector vaccines development.

Myocardial Perfusion Reserve in Children with Friedreich Ataxia

Hutchens JA, Johnson TR, Payne RM.; Pediatric Cardiology. 2021 Jul. DOI: 10.1007/s00246-021-02675-1. 

This retrospective study shows that children with FA develop MPR defects early in the disease process. It also suggests MPR may be a sensitive tool to evaluate underlying cardiac compromise and could be of use in directing surgical management decisions in children with FA.