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Zidovudine ameliorates pathology in the mouse model of Duchenne muscular dystrophy via P2RX7 purinoceptor antagonism

Overview of attention for article published in Acta Neuropathologica Communications, April 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (70th percentile)

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9 tweeters

Citations

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22 Dimensions

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39 Mendeley
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Title
Zidovudine ameliorates pathology in the mouse model of Duchenne muscular dystrophy via P2RX7 purinoceptor antagonism
Published in
Acta Neuropathologica Communications, April 2018
DOI 10.1186/s40478-018-0530-4
Pubmed ID
Authors

Rasha Al-Khalidi, Chiara Panicucci, Paul Cox, Natalia Chira, Justyna Róg, Christopher N. J. Young, Rhiannon E. McGeehan, Kameshwari Ambati, Jayakrishna Ambati, Krzysztof Zabłocki, Elisabetta Gazzerro, Stephen Arkle, Claudio Bruno, Dariusz C. Górecki

Abstract

Duchenne muscular dystrophy (DMD) is the most common inherited muscle disorder that causes severe disability and death of young men. This disease is characterized by progressive muscle degeneration aggravated by sterile inflammation and is also associated with cognitive impairment and low bone density. Given that no current treatment can improve the long-term outcome, approaches with a strong translational potential are urgently needed. Duchenne muscular dystrophy (DMD) alters P2RX7 signaling in both muscle and inflammatory cells and inhibition of this receptor resulted in a significant attenuation of muscle and non-muscle symptoms in DMDmdx mouse model. As P2RX7 is an attractive target in a range of human diseases, specific antagonists have been developed. Yet, these will require lengthy safety testing in the pediatric population of Duchenne muscular dystrophy (DMD) patients. In contrast, Nucleoside Reverse Transcriptase Inhibitors (NRTIs) can act as P2RX7 antagonists and are drugs with an established safety record, including in children. We demonstrate here that AZT (Zidovudine) inhibits P2RX7 functions acting via the same allosteric site as other antagonists. Moreover, short-term AZT treatment at the peak of disease in DMDmdx mice attenuated the phenotype without any detectable side effects. Recovery was evident in the key parameters such as reduced sarcolemma permeability confirmed by lower serum creatine kinase levels and IgG influx into myofibres, decreased inflammatory cell numbers and inflammation markers in leg and heart muscles of treated mice. Moreover, this short-term therapy had some positive impact on muscle strength in vivo and no detrimental effect on mitochondria, which is the main side-effect of Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Given these results, we postulate that AZT could be quickly re-purposed for the treatment of this highly debilitating and lethal disease. This approach is not constrained by causative DMD mutations and may be effective in alleviating both muscle and non-muscle abnormalities.

Twitter Demographics

The data shown below were collected from the profiles of 9 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 18%
Student > Bachelor 7 18%
Student > Postgraduate 4 10%
Student > Master 4 10%
Student > Ph. D. Student 3 8%
Other 7 18%
Unknown 7 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 18%
Medicine and Dentistry 6 15%
Pharmacology, Toxicology and Pharmaceutical Science 3 8%
Neuroscience 2 5%
Business, Management and Accounting 1 3%
Other 8 21%
Unknown 12 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 June 2020.
All research outputs
#4,405,608
of 17,864,600 outputs
Outputs from Acta Neuropathologica Communications
#696
of 1,097 outputs
Outputs of similar age
#84,817
of 289,155 outputs
Outputs of similar age from Acta Neuropathologica Communications
#1
of 1 outputs
Altmetric has tracked 17,864,600 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,097 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.5. This one is in the 36th percentile – i.e., 36% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 289,155 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them