There is a focus on three solutions:
- Correction of the specific PLN mutation in the DNA – DNA research direction
- RNA intervention | Gene silencing – RNA research direction
- Pharmacological therapy
Correction of the specific PLN mutation in the DNA
In this research direction, the focus is on correcting the specific mutation in the DNA, which lies coiled up in the cell nucleus. This technique shows great promise but is also the most complex. Correcting the mutation can be done using two techniques. The most well-known is CRISPR-Cas, and the newer variant is Prime Editing. With CRISPR-Cas, the disadvantage is that while correcting the DNA, other parts are also modified alongside the specific mutation. Prime Editing offers better efficiency, resulting in fewer unintended corrections in the DNA.
RNA intervention | Gene Silencing
The second possibility is to prevent the “faulty/mutated” messenger RNA, which is made in the cell nucleus from the DNA, from being converted into the faulty protein in the cell. This can be achieved by attaching a sort of label to the “faulty/mutated” mRNA, causing it to be degraded in the cell instead of being converted into the mutated PLN protein. Therefore, the research looks into possibilities to intercept the faulty mRNA (messenger in the cell) to prevent the production of faulty PLN protein. Several medications have been brought to the market based on this therapeutic possibility, making the timeline for bringing this to humans more manageable.
The last research direction aims to compensate for the “toxic” effect of the faulty protein in the cell using an existing medication or a medication that needs further refinement. This could also be an existing medication not originally intended for the PLN disease. The advantage of finding an existing medication that can suppress the PLN disease is that it eliminates or significantly reduces the time needed for testing and regulations associated with approving a new medication.