Key points from article :
Rare diseases, affecting a small number of individuals, often lack effective treatments. Many of these diseases are so rare that only a few cases are known worldwide. Antisense oligonucleotides (ASOs) offer hope for personalized treatments for these conditions.
ASOs are short, single, or double-stranded molecules that bind to specific RNA sequences, interfering with gene expression. By targeting disease-causing genes, ASOs can reduce the production of harmful proteins or alter their function. This approach is particularly promising for monogenic rare diseases, which arise from mutations in a single gene.
Several ASO therapies have been approved for various rare diseases. However, developing ASOs for n=1 cases, where only one patient is known, presents unique challenges. Diagnosis can be delayed, and identifying the underlying genetic mutation can be difficult. Even if a mutation is found, creating a suitable ASO can be time-consuming and expensive.
Researchers at the Genomics England Research Summit identified several factors that increase a patient's likelihood of being considered for ASO therapy:
- Patients with rare diseases in "high diagnostic yield" groups, such as neurological disorders, are more likely to be diagnosed due to increased research and a larger patient population.
- Having a diagnosis, understanding the underlying genetic mutation, and identifying a suitable ASO target are crucial factors.
- Patients who have completed standard care and are stable enough to receive long-term treatment are also more likely to be eligible.
- Some mutations may be more suitable for ASO-based therapies than others.
While early treatment is ideal to prevent irreversible damage, delays in diagnosis and ASO development may limit this possibility for some patients. In these cases, ASOs can still offer clinical benefits, such as slowing disease progression. Open communication about the limitations of ASO therapies is essential for managing patient expectations.
Despite these hurdles, ASOs offer the potential for personalized treatments tailored to the specific needs of individual patients. As research progresses and collaborations between academia, industry, and clinicians strengthen, we can hope for more breakthroughs in the treatment of rare diseases.
