Janna Krahe, Ferdinand Binkofski, Jörg B. Schulz, Kathrin Reetz, Sandro Romanzetti,; Neuroscience & Biobehavioral Reviews, 2019, doi:10.1016/j.neubiorev.2019.12.019.
Magnetic resonance spectroscopy (MRS) is applied to investigate the neurochemical profiles of degenerative hereditary ataxias. This meta-analysis provides a quantitative review and reappraisal of MRS findings in spinocerebellar ataxias (SCA) and Friedreich ataxia (FA) available to date. From each study, changes in N-acetyl aspartate (NAA), choline-containing compounds (Cho) and myo-Inositol (mI) ratios to total creatine (Cr) were calculated for groups of patients (1499 patients in total: SCA1 = 223, SCA2 = 298, SCA3 = 711, SCA6 = 165, and FA = 102) relative to their own control group, mostly in cerebellum and pons. SCA1, 2, 3, 6, and FA patients showed overall decreased NAA/Cr compared to controls. Decreased Cho/Cr was visible in SCA1, 2, and 3 and elevated mI/Cr in SCA2 patients in cerebellum. In SCA6 and FA Cho/Cr and mI/Cr did not differ with respect to controls but SCA6 patients indicated higher Cho/Cr compared to SCA1 patients in cerebellum. SCA2 subjects showed the lowest NAA/Cr and Cho/Cr in cerebellum and the highest mI/Cr compared to controls and other genotypes, and therefore the most promising results for a potential biomarker.
Saturday, December 14, 2019
Friday, December 13, 2019
An analysis of orphan medicine expenditure in Europe: is it sustainable?
Jorge Mestre-Ferrandiz, Christina Palaska, Tom Kelly, Adam Hutchings & Adam Parnaby; Orphanet J Rare Dis 14, 287 (2019) doi:10.1186/s13023-019-1246-7
Orphan medicinal product (OMP) prices are considered by some to be a challenge to the sustainability of healthcare expenditure. These concerns are compounded by the increasing number of OMPs receiving marketing authorisation (MA) annually. The aim of this study was to explore the sustainability of OMP expenditure within the context of total European pharmaceutical expenditure.
The EU regulation on OMPs has had success in fostering R&D addressing unmet needs for treatments for rare diseases, with approximately 150 OMPs being approved since its introduction. However, despite the success of the regulation in supporting the development of medicines for rare diseases, the findings from this analysis suggest that the resultant impact on OMP expenditure could be deemed sustainable when seen in the context of total pharmaceutical expenditure.
Orphan medicinal product (OMP) prices are considered by some to be a challenge to the sustainability of healthcare expenditure. These concerns are compounded by the increasing number of OMPs receiving marketing authorisation (MA) annually. The aim of this study was to explore the sustainability of OMP expenditure within the context of total European pharmaceutical expenditure.
The EU regulation on OMPs has had success in fostering R&D addressing unmet needs for treatments for rare diseases, with approximately 150 OMPs being approved since its introduction. However, despite the success of the regulation in supporting the development of medicines for rare diseases, the findings from this analysis suggest that the resultant impact on OMP expenditure could be deemed sustainable when seen in the context of total pharmaceutical expenditure.
Thursday, December 12, 2019
Diagnosis and management of progressive ataxia in adults
Rajith Nilantha de Silva, Julie Vallortigara, Julie Greenfield, Barry Hunt, Paola Giunti, Marios Hadjivassiliou. Practical Neurology 2019;19:196-207. doi:10.1136/practneurol-2018-002096
Progressive ataxia in adults can be difficult to diagnose, owing to its heterogeneity and the rarity of individual causes. Many patients remain undiagnosed (‘idiopathic’ ataxia). This paper provides suggested diagnostic pathways for the general neurologist, based on Ataxia UK’s guidelines for professionals. MR brain scanning can provide diagnostic clues, as well as identify ‘structural’ causes such as tumours and multiple sclerosis. Advances in molecular genetics, including the wider and cheaper availability of ‘next-generation sequencing’, have enabled clinicians to identify many more cases with a genetic cause. Finally, autoimmunity is probably an under-recognised cause of progressive ataxia: as well as patients with antigliadin antibodies there are smaller numbers with various antibodies, including some associated with cancer. There are a few treatable ataxias, but also symptomatic treatments to help people with the spectrum of complications that might accompany progressive ataxias. Multidisciplinary team involvement and allied health professionals’ input are critical to excellent patient care, including in the palliative phase. We can no longer justify a nihilistic approach to the management of ataxia.
Progressive ataxia in adults can be difficult to diagnose, owing to its heterogeneity and the rarity of individual causes. Many patients remain undiagnosed (‘idiopathic’ ataxia). This paper provides suggested diagnostic pathways for the general neurologist, based on Ataxia UK’s guidelines for professionals. MR brain scanning can provide diagnostic clues, as well as identify ‘structural’ causes such as tumours and multiple sclerosis. Advances in molecular genetics, including the wider and cheaper availability of ‘next-generation sequencing’, have enabled clinicians to identify many more cases with a genetic cause. Finally, autoimmunity is probably an under-recognised cause of progressive ataxia: as well as patients with antigliadin antibodies there are smaller numbers with various antibodies, including some associated with cancer. There are a few treatable ataxias, but also symptomatic treatments to help people with the spectrum of complications that might accompany progressive ataxias. Multidisciplinary team involvement and allied health professionals’ input are critical to excellent patient care, including in the palliative phase. We can no longer justify a nihilistic approach to the management of ataxia.
Tuesday, December 10, 2019
NAD+ and Exercise in FA (ExRx in FA)
ClinicalTrials.gov Identifier: NCT04192136. December 10, 2019 Children's Hospital of Philadelphia.
Randomized, placebo-controlled trial with a 2x2 factorial design testing the effects of an NAD+ precursor (NR) and exercise on VO2max and Si in Friedreich's Ataxia (FA).
The primary objective of this research is to measure the effect of combination administration (NR + exercise) on aerobic capacity (VO2max) in FA. A key secondary objective is to measure the effect of combination administration (NR + exercise) on glucose homeostasis (Si) in FA.
Randomized, placebo-controlled trial with a 2x2 factorial design testing the effects of an NAD+ precursor (NR) and exercise on VO2max and Si in Friedreich's Ataxia (FA).
The primary objective of this research is to measure the effect of combination administration (NR + exercise) on aerobic capacity (VO2max) in FA. A key secondary objective is to measure the effect of combination administration (NR + exercise) on glucose homeostasis (Si) in FA.
Sunday, December 8, 2019
Evolutionarily conserved susceptibility of the mitochondrial respiratory chain to SDHI pesticides and its consequence on the impact of SDHIs on human cultured cells
Paule Bénit, Agathe Kahn, Dominique Chretien, Sylvie Bortoli, Laurence Huc, Manuel Schiff, Anne-Paule Gimenez-Roqueplo, Judith Favier, Pierre Gressens, Malgorzata Rak, Pierre Rustin; PLoS ONE 14(11): e0224132. doi:10.1371/journal.pone.0224132
we show that a pre-existing mitochondrial defect, such as partial SDH dysfunction or hypersensitivity to oxidative insults (FRDA, FAD), increases the susceptibility to SDHIs, suggesting a particular risk for individuals with such a dysfunction.
we show that a pre-existing mitochondrial defect, such as partial SDH dysfunction or hypersensitivity to oxidative insults (FRDA, FAD), increases the susceptibility to SDHIs, suggesting a particular risk for individuals with such a dysfunction.
Saturday, December 7, 2019
Effects of tocotrienol supplementation in Friedreich’s ataxia: A model of oxidative stress pathology
Alessandra Bolotta, Antonella Pini, Provvidenza M Abruzzo, Alessandro Ghezzo, Alessandra Modesti, Tania Gamberi, Carla Ferreri, Francesca Bugamelli, Filippo Fortuna, Silvia Vertuani, Stefano Manfredini, Cinzia Zucchini, Marina Marini; Experimental Biology and Medicine. Dec. 2019, doi:10.1177/1535370219890873.
Oxidative stress is involved in the pathogenesis of Friedreich's ataxia (FRDA), a genetic disorder causing neurodegeneration due to the dramatic reduction in the expression of frataxin. To date, no cure is available for FRDA patients. In some countries, FRDA patients assume idebenone in order to counteract the effects of frataxin deficiency. We demonstrate that idebenone treatment alone is not able to abrogate oxidative stress in FRDA patients, whereas the combined treatment with tocotrienols might be more efficient and perhaps produce clinical improvement. In fact, a decrease in oxidative stress and inflammation markers can be seen after two months and is more pronounced after one year of treatment. This is, in our opinion, valuable information for clinicians, since idebenone is the treatment of choice for FRDA patients in some countries.
Oxidative stress is involved in the pathogenesis of Friedreich's ataxia (FRDA), a genetic disorder causing neurodegeneration due to the dramatic reduction in the expression of frataxin. To date, no cure is available for FRDA patients. In some countries, FRDA patients assume idebenone in order to counteract the effects of frataxin deficiency. We demonstrate that idebenone treatment alone is not able to abrogate oxidative stress in FRDA patients, whereas the combined treatment with tocotrienols might be more efficient and perhaps produce clinical improvement. In fact, a decrease in oxidative stress and inflammation markers can be seen after two months and is more pronounced after one year of treatment. This is, in our opinion, valuable information for clinicians, since idebenone is the treatment of choice for FRDA patients in some countries.
Friday, December 6, 2019
The Friedreich’s Ataxia Research Alliance Promotes Jennifer Farmer, MS to Chief Executive Officer
PRESS RELEASE GlobeNewswire, Dec. 5, 2019
DOWNINGTOWN, Pa., Dec. 05, 2019 (GLOBE NEWSWIRE) -- The Board of Directors at The Friedreich’s Ataxia Research Alliance (FARA) today announced the promotion of Jennifer Farmer, MS to the role of Chief Executive Officer (CEO).
DOWNINGTOWN, Pa., Dec. 05, 2019 (GLOBE NEWSWIRE) -- The Board of Directors at The Friedreich’s Ataxia Research Alliance (FARA) today announced the promotion of Jennifer Farmer, MS to the role of Chief Executive Officer (CEO).
L’Associació Francesa de l’atàxia de Friedreich concedeix una ajuda de 25.000 € per validar el potencial terapèutic del calcitriol per tractar aquesta malaltia rara
IRB-Lleida, Dijous, 5 de desembre de 2019
L'Associació Francesa de l'Atàxia de Friedreich ha concedit una ajuda de 25.000 € al Grup de Recerca Bioquímica de l'Estrès Oxidatiu de l'Institut de Recerca Biomèdica de Lleida (IRBLleida) per validar el potencial terapèutic del calcitriol, la forma activa de la vitamina D, per tractar aquesta malaltia. L'investigador principal d'aquest projecte és el doctor Fabien Delaspre.
Les recerques actuals, que s'acabaran de confirmar amb aquest estudi, han demostrat que es tracta d'un model satisfactori per estudiar l'atàxia de Friedreich, ja que mostren nivells baixos (però no nuls) de frataxina i signes de disfunció locomotora.
L'Associació Francesa de l'Atàxia de Friedreich ha concedit una ajuda de 25.000 € al Grup de Recerca Bioquímica de l'Estrès Oxidatiu de l'Institut de Recerca Biomèdica de Lleida (IRBLleida) per validar el potencial terapèutic del calcitriol, la forma activa de la vitamina D, per tractar aquesta malaltia. L'investigador principal d'aquest projecte és el doctor Fabien Delaspre.
Les recerques actuals, que s'acabaran de confirmar amb aquest estudi, han demostrat que es tracta d'un model satisfactori per estudiar l'atàxia de Friedreich, ja que mostren nivells baixos (però no nuls) de frataxina i signes de disfunció locomotora.
Friedreich’s Ataxia: Case series and the Additive Value of Cardiovascular Magnetic Resonance
Mavrogeni Sophie, Giannakopoulou Aikaterini, Katsalouli Marinab, Pons Roser Maria, Papavasiliou Antigoni, Kolovou Genovefa, Noutsias Michel, Papadopoulos George, Karanasios Evangelos, Chrousos George P.; Journal of Neuromuscular Diseases, vol. Pre-press, no. Pre-press, pp. 1-7, 2019 DOI: 10.3233/JND-180373
The combination of classical diagnostic indices and CMR may reveal early asymptomatic FA-CM and motivate the early initiation of cardiac treatment. Furthermore, these indices can be also used to validate specific treatment targets in FA, potentially useful in the prevention of FA-CM.
The combination of classical diagnostic indices and CMR may reveal early asymptomatic FA-CM and motivate the early initiation of cardiac treatment. Furthermore, these indices can be also used to validate specific treatment targets in FA, potentially useful in the prevention of FA-CM.
Tuesday, December 3, 2019
A rare disease patient/caregiver perspective on fair pricing and access to gene-based therapies
White, W.; Gene Ther (2019) doi:10.1038/s41434-019-0110-7
Gene-based therapies are changing the landscape of medicine for patients with rare diseases. Companies should not automatically assume that the combination of the “gene therapy” label and a small patient population justifies high prices. Value determination methods need to provide fair incentives and outcomes to industry, payers, regulators, and especially patients—the courageous pioneers who need equitable and sustainable access to life-changing gene-based therapies.
Gene-based therapies are changing the landscape of medicine for patients with rare diseases. Companies should not automatically assume that the combination of the “gene therapy” label and a small patient population justifies high prices. Value determination methods need to provide fair incentives and outcomes to industry, payers, regulators, and especially patients—the courageous pioneers who need equitable and sustainable access to life-changing gene-based therapies.
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