Cystic Fibrosis (CF), as explained by Berical et al. is a genetic lung disease, caused by a singular gene. As a monogenic lung disease, CF is caused by a mutation on a singular gene, the CFTR gene. This codes for the CFTR protein, a channel protein found in a specific type of cell. This cell lines organs, and functions to move materials within the organs with a hair-like structure called cilia. The CFTR channel functions to move chloride, a negatively charged ion from inside the cell, into the trachea. Once in the trachea, the negative properties of chloride attract the positive hydrogen atoms in a water molecule because as the saying goes; “opposites attract.” Water molecules allow the cilia on the epithelial cells to move, creating a sweeping motion that dislodges the mucus in the trachea. Mucus has the role of trapping inhaled particles from the environment such as dust, dirt, and pollen. Due to the collection of these particles, mucous membranes will increase when an individual is sick. Mucus in the trachea traps microorganisms, such as viruses or bacteria before they enter the lungs. Although mucus is very important in your immune health, excess can become dangerous. When mucus is unable to move, respiratory infections often occur as large concentrations of germs are residing in your airway. Mucus can become idle when there is no water to sweep it, when there is no water, the CFTR channel is not functioning properly. This phenomenon occurs when there is a mutation on the CFTR gene. There are different classes of mutations for the CFTR gene, all of which have unique problems, all leading to the buildup of mucus. (Berical et al., 2022)

Treatment focuses on the management of the disease. There are many techniques and strategies in this management, consisting of behavioral practices, equipment usage, and even drug use. There are many behavioral practices used that focus on breaking up mucus excess in mucous membranes. These practices include; breathing techniques, coughing techniques, and chest physical therapy. (Cleveland Clinic, 2021) Patients may also use medical equipment that disrupts mucus, to break it up. These devices include vibrating vests and vibrating mouthpieces. Another aspect of treatment includes a pharmaceutical approach of antibiotics to combat respiratory infections, anti-inflammatories, pancreatic enzymes for digestion, and stool softeners. There are even surgeries that attempt to improve quality of life. These include transplants, blockage removals, and sinus/nose surgeries. (Johns Hopkins Cystic Fibrosis Center, 2020)

The article, “A multimodal iPSC platform for cystic fibrosis drug testing” focuses on targeted treatment options for individuals with rarer variants. These rarer variants consist of patients with a class 1 mutation of the CFTR gene. This article fixates on treatments for individuals with rarer variants of Cystic Fibrosis as “individuals with CF due to class 1 variants lack targeted therapies and require urgent and ambitious approaches to ameliorate their disease.” (Berical et al., 2022) There are six different classes of CFTR mutations, five of which are referenced in the research article. The experiment encompasses three classes of mutations, classes 1 through 3. 

The purpose of investigating iPSCs as a platform for future treatments and research of cystic fibrosis is to further research on rarer variants of CF. There is a foundational difference between class 1 mutations and other class mutations as class 1 mutations result in a premature tribulation. This timeline eliminates many possible cellular platform options that would otherwise cooperate with the other mutation classes. 

Research is important to many different fields, medicine being one of them. Research for potential treatments, in this context; Cystic Fibrosis, shares the purpose of improving an individual's condition. The lacking platforms available for researching targeted treatments for class 1 mutations has led to a minute selection of options. Individuals with class 1 mutations also experience severe cystic fibrosis, making research and experimentation even more important.

Research of CF requires a cellular platform to experiment with, such as an iPSC. This platform uses body cells from an individual with CF to create stem cells, or cells that can differentiate into many different types of cells. The use of an iPSC-based system using cells from individuals with rare variants grants the ability to produce quantities of disease-relevant CFTR-expressing airway cells, without an invasive biopsy that is typically required. Another benefit of iPSCs is their ability to contain the genetic code of the donor, even revealing the specific CFTR sequence that codes for the mutation. This is essentially beneficial for experiments relating to gene editing. The experiment yielded potential novel agents for class 1 CFTR variants; W1282X and G542X, providing evidence towards the usefulness of this platform type. (Berical et al., 2022)

 There are three primary platforms used in CF treatment research. HBECs, human bronchial epithelial cells, are “the current gold standard cell based platform for preclinical assessment of CFTR mediated ion transport.” (Berical et al., 2022) These cells have a variety of property similarities to the human airway. This allows a predictive response to CFTR modulators, making HBECs the standard for validation of preclinical drug efficacy. Rectal organoids are another platform used by researchers. Organoids are miniature organs that mimic (simplified) functions of a given organ. The use of this platform for CF research can indicate effects from CFTR modulators from individuals with different CFTR variants. The last platform, iPSCs, contain the exact genetic sequence of the donor's CFTR section. This platform can be differentiated into alveolar and airway epithelial cells. 

 Researchers use models to simulate the environment of CF, testing different variables and recording the results. Platforms are necessary for experimentation to take place. Platforms have enabled high throughput screening approaches, leading to the identification of CFTR modulators. The detection of these CFTR modulator effects is possible with these platforms, even with different CFTR variants. Similarities in morphological, molecular, and physiological properties between cell cultures and the in vivo human airway have been recorded. (Berical et al., 2022)

The cells used in iPSC's must be patient specific due to the indefinite factors that make up a human being.  A treatment that works for one patient, may not work for another, which is why these models must be patient specific. Since CF is genetic, the DNA in a somatic cell also plays a large role in these contributing factors. Cell models must be patient specific due to the production of targeted therapeutic treatment options. CF, as a genetic disorder, is unique to every individual affected by it. There are many different factors that impact a patient's specific experience with CF, due to a variety of variants.

Cell models are used to further pharmacotherapy, gene-editing, gene-delivery, and cell-based approaches. These models can be used as predictors of in vivo responses of certain modulators. The effectiveness of a candidate drug is commonly evaluated in cellular platforms, prior to advancement in a clinical trial. The use of platforms furthers the potential of CF treatment research. 

 There are a variety of approaches available for individuals with CF. Although, not all of these approaches are applicable to every patient due to the previously discussed variants. Pharmacotherapy approaches use combinatorial regimes that use read-through molecules. Therapeutic approaches include behavioral changes, equipment, pharmaceutical, and surgical options. Gene-editing is a promising approach to CF that would cure patients, given their given mutation is reversed. (Berical et al., 2022)