Safety and Efficacy Of Interferon γ in Friedreich's Ataxia

Vavla, Marinela; D’Angelo, Maria Grazia; Arrigoni, Filippo; Toschi, Nicola; Peruzzo, Denis; Gandossini, S.; Russo, Annamaria; Diella, Eleonora; Tirelli, Stefania; Salati, R.; Scarpazza, Paolo; Luffarelli, Riccardo; Fortuni, Silvia; Rufini, Alessandra; Condò, Ivano; Testi, Roberto; Martinuzzi, Andrea

doi:10.1002/mds.27979

Cited by 12 publications

(13 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here we describe the functional and the structural modifications occurring in the brain during and after an experimental treatment with IFNγ in a cohort of FRDA patients, with complementary results in support to the significant changes observed with disease-specific clinical measures (SARA and cardiac outcomes) ( Vavla et al, 2020 ).…”

Section: Discussionmentioning

confidence: 56%

“…Detailed clinical and demographic data have been published elsewhere ( Vavla et al, 2020 ). Twelve patients with a mean age of 17.33 ± 4.54 years were recruited and 11 completed the study.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, the clinical and the neuroimaging assessments were administered ∼6 months prior to study initiation (T-6). Detailed information about the clinical study design, inclusion criteria, IFNγ administration, and safety measures have been reported elsewhere ( Vavla et al, 2020 ). The study was approved by the IRB (no.…”

Section: Methodsmentioning

confidence: 99%

“…Interferon gamma (IFNγ), a naturally occurring cytokine which was shown to be able to boost frataxin expression both in vitro and in rodent models ( Tomassini et al, 2012 ), has been tested in several clinical trials. This drug shows a good safety profile and variable levels of efficacy, depending on the different biochemical and clinical measures used ( Seyer et al, 2015 ; Marcotulli et al, 2016 ; Lynch et al, 2019 ; Vavla et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…We performed an open-label, one-step dose escalation phase II clinical trial to assess the safety and the efficacy of IFNγ in FRDA patients. The results were partly published and included a series of objective outcome measures intended to detect changes in multiple affected systems in FRDA ( Vavla et al, 2020 ). The clinical and the cardiac indicators testified for a halt in disease progression and in cardiac wall thickness and pointed out a rebound effect after the termination of treatment.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Sensitivity of Neuroimaging Indicators in Monitoring the Effects of Interferon Gamma Treatment in Friedreich’s Ataxia

et al. 2020

Self Cite

View full text Add to dashboard Cite

The identification of efficient markers of disease progression and response to possibly effective treatments is a key priority for slowly progressive, rare and neurodegenerative diseases, such as Friedreich’s ataxia. Various imaging modalities have documented specific abnormalities in Friedreich’s ataxia that could be tracked to provide useful indicators of efficacy in clinical trials. Advanced MRI imaging (diffusion tensor imaging, DTI; functional MRI, fMRI; and resting-state fMRI, rs-fMRI) and retinal imaging (optical coherence tomography, OCT) were tested longitudinally in a small group of Friedreich’s ataxia patients participating in an open-label clinical trial testing the safety and the efficacy of 6-month treatment with interferon gamma. While the DTI indices documented the slow progression of fractional anisotropy loss, fMRI and rs-fMRI were significantly modified during and after treatment. The fMRI changes significantly correlated with the Scale for the Assessment and Rating of Ataxia, which is used to monitor clinical response. OCT documented the known thickness reduction of the retinal nerve fiber layer thickness, but there was no change over time. This pilot study provides indications for the potential utility of fMRI and rs-fMRI as ancillary measures in clinical trials for Friedreich’s ataxia.

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Sensitivity of Neuroimaging Indicators in Monitoring the Effects of Interferon Gamma Treatment in Friedreich’s Ataxia

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

Therapeutic Use of Interferon Gamma in Friedreich Ataxia

Martinuzzi

Paparella

Vavla

et al. 2023

Contemporary Clinical Neuroscience

View full text Add to dashboard Cite

Therapeutic Biomarkers in Friedreich’s Ataxia: a Systematic Review and Meta-analysis

Gavriilaki,

Chatzikyriakou,

Moschou

et al. 2023

Cerebellum

View full text Add to dashboard Cite

Although a large array of biomarkers have been investigated in Friedreich’s ataxia (FRDA) trials, the optimal biomarker for assessing disease progression or therapeutic benefit has yet to be identified. We searched PubMed, MEDLINE, and EMBASE databases up to June 2023 for any original study (with ≥ 5 participants and ≥ 2 months’ follow-up) reporting the effect of therapeutic interventions on any clinical, cardiac, biochemical, patient-reported outcome measures, imaging, or neurophysiologic biomarker. We also explored the biomarkers’ ability to detect subtle disease progression in untreated patients. The pooled standardized mean difference (SMD) was calculated using a random-effects model. The study’s protocol was registered in PROSPERO (CRD42022319196). In total, 43 studies with 1409 FRDA patients were included in the qualitative synthesis. A statistically significant improvement was observed in Friedreich Ataxia Rating Scale scores [combining Friedreich Ataxia Rating Scale (FARS) and modified FARS (mFARS): SMD = − 0.32 (− 0.62 to − 0.02)] following drugs that augment mitochondrial function in a sensitivity analysis. Left ventricular mass index (LVMI) was improved significantly [SMD = − 0.34 (− 0.5 to − 0.18)] after 28.5 months of treatment with drugs that augment mitochondrial function. However, LVMI remained stable [SMD = 0.05 (− 0.3 to 0.41)] in untreated patients after 6-month follow-up. None of the remaining biomarkers changed significantly following any treatment intervention nor during the natural disease progression. Nevertheless, clinical implications of these results should be interpreted with caution because of low to very low quality of evidence. Further randomized controlled trials of at least 24 months’ duration using a biomarker toolbox rather than a single biomarker are warranted.

show abstract

Safety and Efficacy Of Interferon γ in Friedreich's Ataxia

Cited by 12 publications

References 7 publications

Sensitivity of Neuroimaging Indicators in Monitoring the Effects of Interferon Gamma Treatment in Friedreich’s Ataxia

Sensitivity of Neuroimaging Indicators in Monitoring the Effects of Interferon Gamma Treatment in Friedreich’s Ataxia

Therapeutic Use of Interferon Gamma in Friedreich Ataxia

Therapeutic Biomarkers in Friedreich’s Ataxia: a Systematic Review and Meta-analysis

Contact Info

Product

Resources

About