Novel porosome therapy for CF granted FDA’s orphan drug status
Promising treatment for CF patients, regardless of underlying genetic mutation
The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to Porosome Therapeutics’ new treatment strategy for cystic fibrosis (CF), which is based on the porosome, a type of cellular structure.
The designation is given to boost the development of therapies for rare diseases, which affect fewer than 200,000 people in the U.S. It provides companies with several incentives, including assistance in drug development, exemption from FDA application fees, and seven years of market exclusivity if the treatment is approved.
“We are pleased to receive the Orphan Drug Designation from the FDA because of its life-saving impact on the disease and our drug development roadmap,” Guillermo Marmol, president and CEO of Porosome, said in a company press release.
CF is caused by genetic mutations that disrupt the production or function of CFTR, a protein found on the surface of cells that normally helps regulate the flow of chloride ions across the cell membrane. Without proper CFTR function, mucus becomes abnormally thick and sticky, which drives most disease symptoms.
The porosome is a complex of several proteins, including CFTR, that help regulate the movement of molecules out of cells, and it was discovered by Bhanu P. Jena, PhD, a professor at Wayne State University School of Medicine, in Michigan.
Treatment based on porosome reconstitution
The novel treatment is based on porosome reconstitution, which means introducing healthy porosomes containing functional CFTR, extracted from cells that line the airways, into the membrane of CF cells. It aims to restore normal chloride ion flow and mucus production, regardless of the underlying genetic mutation.
“We’re gratified by the FDA’s recognition of porosome reconstitution therapy as a new and novel approach for treating cystic fibrosis, given its promise to treat all mutations of the disease, including those that result due to the absence of CFTR expression in some patients,” said Jena, who is also the company’s co-founder and chairman.
In a CF cell model carrying F508del, the most common CF-causing mutation, porosome reconstitution boosted the secretion of certain mucus proteins, including MUC5B and MUC5AC. Notably, porosome therapy was significantly more potent on mucus protein secretion than tezacaftor and ivacaftor, which are approved CFTR modulators that increase faulty CFTR protein function.
In a CF mouse harboring the same mutation, porosome therapy normalized CFTR function, as indicated by the nasal potential difference. This test measures a small electrical charge in the airway lining of the nose.
“It’s heartening to see the porosome discovery made 30 years ago is now being translated to serve humanity,” Jena added.
About the Author
