Cystic Fibrosis Foundation Funds Feldan Shuttle for Medicine Delivery

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by Steve Bryson, PhD |

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The Cystic Fibrosis Foundation has awarded funding to Feldan Therapeutics to develop the Feldan Shuttle, a technology designed to deliver medicines directly inside the epithelial cells that line the airways in people with cystic fibrosis (CF).

Awarded as part of the foundation’s $500 million Path to a Cure initiative, the funds will accelerate the development of treatments targeting the underlying cause of CF.

“We are very enthusiastic about this support from the Cystic Fibrosis Foundation,” François-Thomas Michaud, PhD, co-founder and CEO of Feldan, said in a press release. “We are looking forward to advancing safe delivery of chemical and biological cargos to CF airway epithelia through this grant and taking an active role in offering new therapeutic avenues to CF patients.”

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In CF, due to a faulty CFTR channel protein, epithelial cells of the airways cannot properly regulate the flow of salt and water across their membranes, resulting in thick and sticky mucus production.

CF therapeutics administered to the airways are often blocked by the specialized cells, secreted immune signaling proteins, and the mucociliary transport system — the self-cleaning mechanism of the airways that removes particulates and microbes.

The delivery of biological agents inside cells relies on the endocytic pathway, whereby the medicine is surrounded by an area of the cell membrane, which then buds off inside the cell to form a small spherical compartment called an endosome. However, in a process known as endosomal entrapment, the medicine remains inside endosomes and is eventually degraded.

Based on naturally occurring, cell-penetrating proteins, the Feldan Shuttle is a short peptide (a short chain of amino acids, the building blocks of proteins) designed to circumvent endosomal entrapment. First, the Shuttle binds tightly to cell membranes, initiating the endocytic pathway; then it promotes leakage in the endosomes, allowing the therapeutic agents — from small molecules to proteins — to flow into the cell.

The potential of this technology was described in a study published in the journal Nature Communications. Using cell-based models and mice, the authors demonstrated that the Shuttle effectively delivered gene-editing peptides into specialized airway epithelial cells, which edited genes at a clinically relevant level without signs of toxicity.

According to the company, the Shuttle also degrades quickly, leaves no toxic metabolites, is safe for use in vivo (in a living organism), and delivers to multiple cell types.

In addition to lung applications, the company also focuses on skin conditions.