Current and Future Research into Cystic Fibrosis

Just 50 years ago, no treatments for cystic fibrosis (CF) existed. Many families and scientists gathered together under the umbrella of the Cystic Fibrosis Foundation to raise millions of dollars that today funds medical research into CF. Today doctors understand the disease much better. There are many effective drugs and other therapies help keep people with CF live longer than ever.

Current research includes studies that seek to find answers on the physical complications and behavioral aspects of CF, as well as the cost-effectiveness of new versus old treatments. Clinical trials are the method used to find new medical advances.

Clinical trials

Clinical trials are studies performed under controlled conditions. The goal of a clinical trial is to gather evidence (data) to find out whether a new drug or new treatment regimen is effective for someone with a specific condition or has higher efficacy than older drugs or treatments. These studies also look to determine what side effects, if any, a new medicine or device might have.

The U.S. Food and Drug Administration (FDA) approves and oversees all clinical trials conducted in the U.S. In addition, individual hospitals oversee clinical trials through institutional review boards (IRBs) which review the way a study is designed and any supporting research to protect patients.

Clinical trials follow a protocol (plan) that outlines who can participate (e.g. people with CF over 18), what tests the person will receive and how often, and what type of data will be collected. In the case of CF, many potential new drugs target certain genetic mutations, such as F508del. Therefore, people with other types of mutations are not eligible to participate in that trial.

Clinical trial phases

Clinical trials come in distinct phases, each designed to test the safety and usefulness of the new drug or treatment:

• The pretrial phase is conducted on animals other than humans to determine basic safety.
• Phase 1 lasts 1 month, and includes roughly 10-20 healthy people without CF.
• Phase 2 lasts 3-12 months and includes 50-75 people with CF.
• Phase 3 lasts 6-12 months and includes 100-300 people with CF.
• If found safe, the drug or device company files for FDA approval in a process that generally takes 6-12 months.
• Phase 4 lasts 3-12 months and includes 100-300 people with CF.¹

Often, any medical care related to the trial is provided to the patient at no cost because it is experimental.

Types of cystic fibrosis research

The complications of CF caused by CFTR malfunction include lung infections, inflammation, excess mucus, and gastrointestinal issues. Research into these complications seeks to find better treatments that ultimately lead to longer, healthier lives for people with CF. Investigations into the CFTR protein seek to understand how the protein works so that new drugs can restore proper function.

Research into nonsense and rare CF mutations

Early cystic fibrosis research naturally focused on treatments for the most common genetic mutations. However, now that CFTR modulators are available to help many with CF, research is starting to look at what are called nonsense and rare mutations.

Nonsense and rare mutations occur in about 7% of people with CF. These people do not produce any CFTR protein, so CFTR modulators do not work to fix the underlying cause of their disease. These mutations will require a totally different approach to fixing their CFTR protein.²

Gene therapy and gene editing

Gene editing is a process that uses the cell’s own DNA to correct the CFTR mutation so that normal CFTR proteins are supplied to cells. CRISPR/cas9 is the most versatile, most inexpensive gene-editing tool in use today.³ Gene therapy is a process that places a new, correct version of the CFTR gene into the cells of a person’s body. This research is still highly experimental and is many years away from practical application.⁴

CF drug development pipeline

You can check on the many drugs under development today using the CF Foundation’s Drug Development Pipeline Tool.⁵ This tool allows the user to search potential new therapies by the phase of the drug trial or by the problem the drug aims to fix, such as CFTR function, mucus clearance, or lung infections.