[Interfering RNA and antisense oligonucleotide treatments currently available in France: An update]
1Académie nationale de médecine, 16, rue Bonaparte, 75006 Paris, France.
Abstract:
The arrival of anti-Covid-19 RNA vaccines in 2020 should not obscure the fact that for several years we have already had treatments based on interfering RNA or antisense oligonucleotides in a number of rare diseases with a very poor prognosis such as transthyretin amyloidosis, acute hepatic porphyria, primary hyperoxaluria, spinal muscular atrophy or familial hyperchylomicronemia. If their performance, unlike that of vaccines, is for the moment only qualified as moderate therapeutic progress (moderate clinical added value) in the therapeutic strategies against these diseases, it should be taken into account that their initial evaluation was penalized by a certain number of unfavorable factors: trials of small numbers, therapeutic modalities to be refined, the lack of hindsight on their long-term effects but especially the choice of the moment of the initiation of the treatment in the natural evolution of the sickness. This choice is not trivial because it is hard to imagine that the products used could, beyond a simple stabilization of the disease installed, allow its regression as soon as certain lesions formed are irreversible. This is why their very early implementation, possibly based on genetic screening, is an avenue to be seized in the interest of patients. But, in the competitive context of innovations in the field, interfering RNAs and antisense oligonucleotides will have to reckon with gene therapy and genome editing using the CRISPR-Cas 9 technique.
Insights
RNA-based therapies like interfering RNA and antisense oligonucleotides offer moderate progress for rare genetic diseases. Early intervention, potentially via genetic screening, is crucial for maximizing patient benefit.
Area of Science:
- Nucleic acid-based therapeutics
- Rare genetic diseases
- RNA interference (RNAi) and antisense oligonucleotide (ASO) technology
Context:
- While COVID-19 RNA vaccines gained prominence in 2020, RNA-based therapies have been used for years in rare diseases.
- Existing treatments include interfering RNA (iRNA) and antisense oligonucleotides (ASOs) for conditions like transthyretin amyloidosis and spinal muscular atrophy.
- These therapies have shown moderate therapeutic progress, with evaluations impacted by small trial sizes and evolving treatment strategies.
Purpose:
- To assess the current status and future potential of iRNA and ASO therapies in treating rare genetic disorders.
- To highlight the importance of early treatment initiation for maximizing therapeutic efficacy.
- To contextualize these therapies within the broader landscape of genetic medicine, including gene therapy and CRISPR-Cas9.
Summary:
- Interfering RNA and antisense oligonucleotides represent established therapeutic modalities for rare, severe genetic diseases, offering moderate clinical benefits.
- Initial evaluations were challenged by small patient cohorts, the need for refined treatment protocols, and limited long-term data.
- The timing of intervention is critical; early treatment, ideally identified through genetic screening, is essential to prevent irreversible disease progression.
Impact:
- Early implementation of iRNA and ASO therapies, guided by genetic screening, represents a significant opportunity to improve patient outcomes in rare diseases.
- These RNA-based approaches face increasing competition from emerging gene therapy and genome editing technologies like CRISPR-Cas9.
- Continued research and optimized treatment strategies are necessary to fully realize the potential of RNA-based therapeutics in genetic medicine.
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