mRNA therapies for treatment of Cystic Fibrosis
- Deepti Kumar
- 10 hours ago
- 2 min read
Photo Credit: Wix
Cystic fibrosis is an autosomal recessive disorder, causes by mutations in the CFTR gene. It affects approx. 105,000 people worldwide. Before CFTR modulators were developed to treat cystic fibrosis, patients with CF rarely survived beyond their 20’s. With the advent of these transformative therapies patients with CF live well into their 60’s and 70’s. While CFTR modulators offer hope to 90% of the patients, many still are unable to benefit. About 10% of patients have rare mutations and do not respond to modulators. Many patients are unable to take medications due to side effects or underlying health conditions. Gene therapies such as mRNA therapies can offer hope to these patients.
what is mRNA therapy?
In order to understand mRNA therapy, it is important to first understand the flow of genetic information in our cells. Genes are sequences of DNA that contains the necessary information to make a functional protein. This happens in a two-step process. The DNA is first transcribed into messenger RNA (mRNA). The mRNA is then translated into protein. The mRNA therapy for CF aims to deliver the corrected copy of the CFTR mRNA that instructs the lung cell to produce healthy CFTR protein. If successful, this therapy could work for any person with CF regardless of the CFTR mutation they carry.
Current mRNA therapies in clinical trials
There are currently 2 mRNA therapies in phase2 clinical trials
ARCT-032 (LUNAR-CF) (Arcturus Therapeutics)
Inhaled therapy that aims to deliver a correct copy of the CFTR mRNA to the lung cells via. lipid mediated delivery system called LUNAR.
Lung cells will then use the instructions from this mRNA to make a functional CFTR protein.
Could be used in any patient with CF, including those with ultra-rare or non-sense mutations.
RCT2100 (ReCode Therapeutics)
Inhaled therapy that uses lipid nano-particles to deliver the correct CFTR mRNA copy to the lung cells.
This therapy could be used for all CF patients regardless of the type of CFTR mutation.
The study is testing RCT2100 in combination with Ivacaftor (CFTR modulator).
What are the advantages and challenges of mRNA therapies?
One of the advantages is that it does not disrupt a person’s DNA.
A disadvantage is that mRNA is not very stable and gets broken down inside the cell.
Hence the mRNA therapy would last for only one-two weeks.
Treatment would need to be re-dosed regularly for the mRNA therapy to work.
Conclusions
Genetic approaches to treat CF is a major step forward in the quest to find a cure for all. Despite the optimism, worries remain regarding the best way to deliver these therapies. The lungs diverge into smaller and smaller parts and to reach these smallest and deepest part of the lung epithelium is the greatest challenge. Also, the safety of these treatments is a concern for patients whose only option might be to take gene therapy.
Sources
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