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May 27, 2026Neurology International0 citationsOpen Access

Nucleoside-Analog Reverse-Transcriptase Inhibitors (NRTIs) Against Multiple Sclerosis: Comprehensive Review on a Possible Novel Therapeutic Approach

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AMAlfonso MartinisiUniversità della Svizzera italianaPPPaolo PaganettiBracco (Switzerland)

Key Result

Nucleoside-analog Reverse Transcriptase Inhibitors (NRTIs) are proposed as a potential novel therapeutic approach to target the HERV-W envelope protein and promote remyelination in multiple sclerosis.

Key Points

  • This review aims to investigate NRTIs as a potential therapeutic approach against multiple sclerosis, focusing on their effect on the HERV-W envelope protein.
  • Reviewed literature linking Epstein-Barr Virus to multiple sclerosis incidence.
  • Analyzed clinical cases of antiretroviral drugs tested in multiple sclerosis patients.
  • Evaluated the therapeutic potential of NRTIs in promoting remyelination by targeting HERV-W.
  • HERV-W envelope protein found elevated in multiple sclerosis patients, suggesting its role in disease progression.
  • Review identifies NRTIs as a promising therapeutic strategy for enhancing remyelination.
  • Clinical testing of antiretroviral drugs yielded mixed results, highlighting the need for targeted approaches.

Structured PICO

Do Nucleoside-analog Reverse Transcriptase Inhibitors (NRTIs) improve remyelination and disease progression in patients with multiple sclerosis?

P
Population
Patients with multiple sclerosis
I
Intervention
Nucleoside-analog Reverse Transcriptase Inhibitors (NRTIs)
O
Outcome
Remyelination and disease progression

This review proposes a novel therapeutic rationale for using NRTIs to target HERV-W envelope protein and promote remyelination in multiple sclerosis.

Abstract

To this day, the etiology of multiple sclerosis has yet to be fully comprehended by the scientific community. However, the knowledge on mechanisms leading to the development of this neurodegenerative autoimmune disorder increases daily, along with the development of new disease-modifying treatments. A correlation between Epstein–Barr Virus infection and the disease incidence has recently shed light on possible innovative antiviral therapies. Here, we review the literature on Human Endogenous Retroviral sequences as emerging actors for the impairment of remyelination as a major challenge in disease progression. Our primary focus is the HERV-W envelope protein, which has been found at elevated levels in individuals affected by this condition and is suggested here as a potential therapeutic target. We then continue analyzing the clinical cases where antiretroviral drugs have been tested to treat multiple sclerosis patients and, from successes and failures, we finally narrow down our therapeutic hypothesis to the administration of Nucleoside-analog Reverse Transcriptase Inhibitors to target the HERV-W envelope protein, possibly leading to remyelination and significantly improving the condition of those affected by the disease. The main purpose of this review is to present a rationale for the therapeutic potential of this drug class and offer a new perspective for therapeutic options against multiple sclerosis.

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Cite This Study

Martinisi et al. (2026) conducted a review in Multiple Sclerosis. Nucleoside-analog Reverse Transcriptase Inhibitors (NRTIs) was evaluated. Nucleoside-analog Reverse Transcriptase Inhibitors (NRTIs) are proposed as a potential novel therapeutic approach to target the HERV-W envelope protein and promote remyelination in multiple sclerosis.

synapsesocial.com/papers/6a168b040c924ddd1bd59be6https://doi.org/10.3390/neurolint18050089
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