Bürk K; Cerebellum Ataxias. 2017 Apr 7;4:4. doi: 10.1186/s40673-017-0062-x. eCollection 2017.
This review gives an overview over clinical and genetic aspects of FA and discusses current concepts of frataxin biogenesis and function as well as new therapeutic strategies.
Saturday, April 15, 2017
Friday, April 14, 2017
Australian children living with rare diseases: experiences of diagnosis and perceived consequences of diagnostic delays
Yvonne Zurynski, Marie Deverell, Troy Dalkeith, Sandra Johnson, John Christodoulou, Helen Leonard, Elizabeth J Elliott and APSU Rare Diseases Impacts on Families Study group; Orphanet Journal of Rare Diseases201712:68 DOI: 10.1186/s13023-017-0622-4; Published: 11 April 2017
Parents of children living with rare chronic and complex diseases have called for better education, resourcing of health professionals to prevent avoidable diagnostic delays, and to facilitate access to early interventions and treatments. Access to psychological support and genetic counselling should be available to all parents receiving a life-changing diagnosis for their child.
The most common perceived reasons for delayed diagnosis reported by parents participating in our study was the lack of knowledge among health professionals.
Receiving a diagnosis of a rare chronic and complex disease for their child is a life-changing event for many families, and most require support at or near the time that diagnosis is made. Almost all parents in our study believed that psychological support should always be offered at the time of diagnosis.
Parents believe that health professionals’ knowledge about rare diseases needs to improve to enable more timely diagnosis, treatment, and provision of accurate information about the implications of the disease to families who are stressed, frustrated and anxious. The integration of genomic medicine into the health system, the establishment of multidisciplinary specialist clinics, and clear referral pathways may improve the timeliness and accuracy of diagnosis for children with rare diseases. The ultimate aim should be to improve patient and family experiences, and it is therefore imperative that patients are involved in development and evaluation of such programs.
Parents of children living with rare chronic and complex diseases have called for better education, resourcing of health professionals to prevent avoidable diagnostic delays, and to facilitate access to early interventions and treatments. Access to psychological support and genetic counselling should be available to all parents receiving a life-changing diagnosis for their child.
The most common perceived reasons for delayed diagnosis reported by parents participating in our study was the lack of knowledge among health professionals.
Receiving a diagnosis of a rare chronic and complex disease for their child is a life-changing event for many families, and most require support at or near the time that diagnosis is made. Almost all parents in our study believed that psychological support should always be offered at the time of diagnosis.
Parents believe that health professionals’ knowledge about rare diseases needs to improve to enable more timely diagnosis, treatment, and provision of accurate information about the implications of the disease to families who are stressed, frustrated and anxious. The integration of genomic medicine into the health system, the establishment of multidisciplinary specialist clinics, and clear referral pathways may improve the timeliness and accuracy of diagnosis for children with rare diseases. The ultimate aim should be to improve patient and family experiences, and it is therefore imperative that patients are involved in development and evaluation of such programs.
Thursday, April 13, 2017
No changes in heme synthesis in human Friedreich´s ataxia erythroid progenitor cells
Hannes Steinkellner, Himanshu Narayan Singh, Martina U. Muckenthaler, Hans Goldenberg, Rajeswari R. Moganty, Barbara Scheiber-Mojdehkar, Brigitte Sturm, Gene, Available online 12 April 2017, ISSN 0378-1119, doi:10.1016/j.gene.2017.04.014.
The mystery about the involvement of frataxin on iron metabolism raises the question why frataxin deficiency in primary FRDA cells did not lead to changes in biochemical parameters of heme synthesis. It seems that alternative pathways can circumvent the impact of frataxin deficiency on heme synthesis. We show for the first time in primary FRDA patient cells that reduced frataxin levels are still sufficient for heme synthesis and possibly other mechanisms can overcome reduced frataxin levels in this process. Our data strongly support the fact that so far no anemia in FRDA patients was reported.
FRDA patient cells showed no significant changes in iron levels, hemoglobin synthesis, protoporphyrin IX levels, and ferrochelatase activity. Microarray analysis presented 11 genes that were significantly changed in all patients compared to controls. The genes are especially involved in oxidative stress, iron homeostasis and angiogenesis.
The mystery about the involvement of frataxin on iron metabolism raises the question why frataxin deficiency in primary FRDA cells did not lead to changes in biochemical parameters of heme synthesis. It seems that alternative pathways can circumvent the impact of frataxin deficiency on heme synthesis. We show for the first time in primary FRDA patient cells that reduced frataxin levels are still sufficient for heme synthesis and possibly other mechanisms can overcome reduced frataxin levels in this process. Our data strongly support the fact that so far no anemia in FRDA patients was reported.
FRDA patient cells showed no significant changes in iron levels, hemoglobin synthesis, protoporphyrin IX levels, and ferrochelatase activity. Microarray analysis presented 11 genes that were significantly changed in all patients compared to controls. The genes are especially involved in oxidative stress, iron homeostasis and angiogenesis.
Wednesday, April 12, 2017
Drugmakers accused of exploiting orphan drug incentives, fueling price problem
Brady Huggett, Nature Biotechnology 35, 301 (2017) doi:10.1038/nbt0417-301 Published online 11 April 2017
n January Kaiser Health News published a data-rich report focusing on the increase in approvals of orphan disease drugs, detailing how even high-volume products have reaped the tax breaks and market exclusivity that come with orphan drug status.
For each approval, drugmakers receive government incentives plus seven years exclusivity for that rare disease. Orphan status became a commercial opportunity.
Orphan drug rules “appear to be stretched beyond their original intent,” which may be helping to stoke drug prices for commonly used drugs.
n January Kaiser Health News published a data-rich report focusing on the increase in approvals of orphan disease drugs, detailing how even high-volume products have reaped the tax breaks and market exclusivity that come with orphan drug status.
For each approval, drugmakers receive government incentives plus seven years exclusivity for that rare disease. Orphan status became a commercial opportunity.
Orphan drug rules “appear to be stretched beyond their original intent,” which may be helping to stoke drug prices for commonly used drugs.
Tuesday, April 11, 2017
Biogen Accused Of Stifling Neurological Drug Competition
Law360, Los Angeles (April 4, 2017, 7:05 PM EDT) -- Biogen Inc. is facing an antitrust suit in California federal court filed Tuesday by Ixchel Pharma LLC alleging it attempted to hold a monopoly on drug treatments containing dimethyl fumarate, preventing Ixchel from creating a drug for a degenerative neurological disease.
The complaint claims Biogen specifically stopped a partnership between Ixchel and a competitor to develop a new treatment for Friedreich’s ataxia, a debilitating neuro-degenerative disorder. The condition doesn’t have an FDA-approved treatment, the complaint says, but Ixchel since 2012 has been working to develop one....
The complaint claims Biogen specifically stopped a partnership between Ixchel and a competitor to develop a new treatment for Friedreich’s ataxia, a debilitating neuro-degenerative disorder. The condition doesn’t have an FDA-approved treatment, the complaint says, but Ixchel since 2012 has been working to develop one....
Saturday, April 8, 2017
SNPs in microRNA target sites and their potential role in human disease
Adrianna Moszyńska, Magdalena Gebert, James F. Collawn, Rafał Bartoszewski; Open Biology, The Royal Society Publishing, Published 5 April 2017.DOI: 10.1098/rsob.170019
FXN | miR-124-3p: Reduced expression of the mitochondrial frataxin (FXN) protein has been postulated to play a role in Friedreich's ataxia (FRDA), an inherited neurodegenerative disease. Lower levels of frataxin are due to GAA repeat expansion in the FXN gene. Additionally, Bandiera et al. have suggested that miR-124-3p regulates FXN expression in vivo only in FRDA patients. They identified seven SNPs in the 3′-UTR of FXN in children and adults diagnosed with FRDA. One of them, rs11145043 (G>T), permits miR-124-3p binding only when the T allele is present. Although miR-124-3p is highly expressed in the nervous system, it is overexpressed in FRDA patients, suggesting its role in FRDA. However, its influence on FXN needs further clarification.
FXN | miR-124-3p: Reduced expression of the mitochondrial frataxin (FXN) protein has been postulated to play a role in Friedreich's ataxia (FRDA), an inherited neurodegenerative disease. Lower levels of frataxin are due to GAA repeat expansion in the FXN gene. Additionally, Bandiera et al. have suggested that miR-124-3p regulates FXN expression in vivo only in FRDA patients. They identified seven SNPs in the 3′-UTR of FXN in children and adults diagnosed with FRDA. One of them, rs11145043 (G>T), permits miR-124-3p binding only when the T allele is present. Although miR-124-3p is highly expressed in the nervous system, it is overexpressed in FRDA patients, suggesting its role in FRDA. However, its influence on FXN needs further clarification.
Wednesday, April 5, 2017
New research front to tackle Friedreich’s Ataxia
IRB Barcelona, 14 Mar 2017. IRB Barcelona starts a project with the long-term goal to achieve an injectable frataxin treatment able to reach the brain. The project specifically aims to complete a step necessary in order to move towards a future frataxin replacement therapy for the brain, where the reduction of this protein causes the most damage in patients with Friedreich’s Ataxia.
The study is headed by Ernest Giralt, head of the Peptides and Proteins Lab, who has many years of experience and is a recognised expert in peptide chemistry and new systems of through which to delivery drugs to the brain, such as peptide shuttles—molecules that have the capacity to carry the drug across the barrier that surrounds and protects the brain. Since the lab started its relation with these patients’ associations in 2013*, it has been developing another two projects into Friedrich’s Ataxia.
The study is headed by Ernest Giralt, head of the Peptides and Proteins Lab, who has many years of experience and is a recognised expert in peptide chemistry and new systems of through which to delivery drugs to the brain, such as peptide shuttles—molecules that have the capacity to carry the drug across the barrier that surrounds and protects the brain. Since the lab started its relation with these patients’ associations in 2013*, it has been developing another two projects into Friedrich’s Ataxia.
Monday, April 3, 2017
Reata Pharmaceuticals, Inc. Secures $35 Million Term Loan Facility
IRVING, Texas, April 03, 2017 (GLOBE NEWSWIRE) -- Reata Pharmaceuticals, Inc. (Nasdaq:RETA) (“Reata” or “the Company”), a clinical-stage biopharmaceutical company, today announced that it entered into a $35 million loan and security agreement with Oxford Finance LLC and Silicon Valley Bank. Proceeds from the loan will be utilized primarily to support Reata’s multiple Phase 2 and 3 clinical trial programs for bardoxolone methyl and omavaloxolone.
The loan proceeds are available to Reata in two tranches. The first $20 million tranche was funded on Friday, March 31st. The additional $15 million tranche will be available to Reata from July 1, 2017 to March 31, 2018, and after Reata enrolls the first patient in either (a) the Phase 3 portion of the ongoing Phase 2/3 clinical trial of bardoxolone methyl in chronic kidney disease caused by Alport syndrome or (b) Part 2 of the ongoing two-part clinical trial, or a separate Phase 3 clinical trial, of omavaloxolone in Friedreich’s ataxia.
The loan proceeds are available to Reata in two tranches. The first $20 million tranche was funded on Friday, March 31st. The additional $15 million tranche will be available to Reata from July 1, 2017 to March 31, 2018, and after Reata enrolls the first patient in either (a) the Phase 3 portion of the ongoing Phase 2/3 clinical trial of bardoxolone methyl in chronic kidney disease caused by Alport syndrome or (b) Part 2 of the ongoing two-part clinical trial, or a separate Phase 3 clinical trial, of omavaloxolone in Friedreich’s ataxia.
Sunday, April 2, 2017
Characteristics of Friedreich’s Ataxia and Autosomal Dominant Spinocerebellar Ataxia Types 1, 2, 3, and 6
Pınar Bengi Boz, Filiz Koç, Sabriye Kocatürk Sel, Ali İrfan Güzel, Halil Kasap, Arch Neuropsychiatry 2016; 53: 115-119, DOI:10.5152/npa.2015.9925
This study aimed to analyze the genotypic characteristics of Friedreich’s ataxia (FA) and autosomal dominant ataxias [such as spinocerebellar ataxia (SCA) types 1, 2, 3, and 6] using molecular and biological methods in hereditary cerebellar ataxia considering both clinical and electrophysiological findings.
In our study, 47.2% of patients with FA had developed hereditary cerebellar ataxia. Ground and autosomal dominant-linked SCA1 and SCA6 were each detected in one family. These data suggest that patients with cerebellar ataxia of hereditary origin should be primarily examined for FA.
This study aimed to analyze the genotypic characteristics of Friedreich’s ataxia (FA) and autosomal dominant ataxias [such as spinocerebellar ataxia (SCA) types 1, 2, 3, and 6] using molecular and biological methods in hereditary cerebellar ataxia considering both clinical and electrophysiological findings.
In our study, 47.2% of patients with FA had developed hereditary cerebellar ataxia. Ground and autosomal dominant-linked SCA1 and SCA6 were each detected in one family. These data suggest that patients with cerebellar ataxia of hereditary origin should be primarily examined for FA.
Friday, March 31, 2017
Longitudinal Gait and Balance Decline in Friedreich’s Ataxia: A Pilot Study
Theresa A. Zesiewicz, Jeannie B. Stephenson, Seok Hun Kim, Kelly L. Sullivan, Israt Jahan, Yangxin Huang, Jason L. Salemi, Lynn Wecker, Jessica D. Shaw, Clifton L. Gooch, Gait & Posture, Available online 30 March 2017, ISSN 0966-6362, doi:10.1016/j.gaitpost.2017.03.019.
In the FA group, comfortable and fast gait velocity declined 8.0% and 13.9% after 12 months and 24.1% and 30.3% after 24 months, respectively. Postural stability indices increased in FA subjects an average of 41% from baseline to 24 months, representing a decline in balance. Subjects with FA also demonstrated a 17.7% increase in FARS neurological exam scores over 24 months. There were no changes in gait or balance variables in controls. In the FA group, multiple gait and balance measures correlated significantly with FARS neurological exam scores.
The GAITRite and Biodex systems provided objective and clinically relevant measures of functional decline in subjects with FA that correlated significantly with performance measures in the FARS. Gait velocity may be an important objective measure to identify disease progression in adults with FA.
In the FA group, comfortable and fast gait velocity declined 8.0% and 13.9% after 12 months and 24.1% and 30.3% after 24 months, respectively. Postural stability indices increased in FA subjects an average of 41% from baseline to 24 months, representing a decline in balance. Subjects with FA also demonstrated a 17.7% increase in FARS neurological exam scores over 24 months. There were no changes in gait or balance variables in controls. In the FA group, multiple gait and balance measures correlated significantly with FARS neurological exam scores.
The GAITRite and Biodex systems provided objective and clinically relevant measures of functional decline in subjects with FA that correlated significantly with performance measures in the FARS. Gait velocity may be an important objective measure to identify disease progression in adults with FA.
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