Recent advances in gene-silencing and gene-editing therapies have demonstrated significant potential in altering the treatment landscape for transthyretin (TTR) amyloidosis, transforming the disease’s perception from universally progressive and fatal to treatable with highly specific and effective therapies.
- Gene-silencing and gene-editing therapies have led to substantial improvement in outcomes for patients with ATTR polyneuropathy.
- Small-scale studies of gene silencers in ATTR cardiomyopathy treatment have shown promising results, with large-scale trials expected soon.
- Long-term safety, potential off-target gene editing, and monitoring of cardiac response to treatment remain important questions regarding these novel therapies.
ATTR amyloidosis, a debilitating and life-threatening disease, is caused by misfolding of the TTR protein. Recent advances in gene silencer and gene-editing therapies have demonstrated significant potential in altering the treatment landscape for this disease. With the development of small interfering RNA (siRNA) and antisense oligonucleotide (ASO) drugs, the perception of ATTR amyloidosis has shifted from that of a universally progressive and fatal disease to one that is treatable with highly specific and effective therapies.
Gene Silencers in ATTR Cardiomyopathy Treatment
According to a review published in the journal BioDrugs, gene silencers have resulted in substantial improvement in outcomes for patients with ATTR polyneuropathy. Small-scale studies assessing the use of gene silencers in the treatment of ATTR cardiomyopathy have yielded promising results, and large-scale trials are expected shortly. If successful, gene silencers may be approved for the treatment of ATTR cardiomyopathy in the near future.
Combination Therapy and Earlier Diagnosis
Combining gene silencers and editing therapies with TTR stabilizers may augment their therapeutic efficacy, but more data are needed. Advances in cardiac imaging and increased awareness among clinicians have contributed to earlier diagnosis of ATTR cardiomyopathy, which may lead to better clinical outcomes when using these therapies.
Comparisons Between Different Gene-Silencing and Gene-Editing Therapies
The last decade has seen incredible advances in the treatment of ATTR amyloidosis, with gene silencers such as patisiran, vutrisiran, and inotersen transforming the treatment landscape. Eplontersen, an ASO with a favorable safety profile, and CRISPR/Cas9 in vivo gene editing offer additional promising treatment options. The long-term effects of these drugs, in terms of efficacy and safety, remain to be determined.
The emergence of novel gene-silencing and gene-editing therapies has rapidly expanded the available treatments for ATTR amyloidosis, resulting in tremendous improvements in patient outcomes. As large-scale clinical trials continue, a further expansion of medicines licensed for treatment of ATTR amyloidosis is expected.
Source:
Ioannou, A., Fontana, M., & Gillmore, J. D. (2023). RNA Targeting and Gene Editing Strategies for Transthyretin Amyloidosis. Biodrugs, 37(2), 127-142. https://doi.org/10.1007/s40259-023-00577-7
