The National Institutes of Health (NIH) has awarded $2.9 million to the Arkansas Children’s Research Institute (ACRI) to investigate methods of enhancing the effectiveness of a critical therapy for cystic fibrosis (CF). The five-year study, led by Dr. Jennifer S. Guimbellot, aims to personalize treatment by determining the optimal drug concentration and dosing for individual patients, potentially improving lung function and therapy tolerance.
Revolutionizing CF Care with Triple Combination Therapy
Since the FDA approved triple combination therapy in 2019, CF care has been revolutionized. This therapy corrects the defective protein in many patients, helping maintain the balance of salt and water in affected organs. The result is thinned mucus and reduced risk of infection and inflammation, which greatly improves quality of life and extends lifespan. According to Guimbellot, patients are now engaging in activities that were previously limited, such as running marathons and planning long-term careers and families.
Addressing Challenges with Triple Combination Therapy
Despite the success of triple combination therapy, a significant number of CF patients do not show the same robust response, and others experience side effects like drug-induced liver injury or neuropsychological issues. Recent studies indicate that most patients will encounter some form of side effect, but the overall benefits generally outweigh these challenges, prompting continued use.
Investigating Personalized Dosing and Genetic Factors
Guimbellot and her team hypothesize that the body's handling of the drug may influence a patient's response. They are exploring whether genetic variations could alter drug activity, leading to reduced effectiveness and varying side effects. The team will conduct an observational study to determine if a precise dose exists that optimizes lung function and minimizes side effects for each patient.
A Patient-Centered Approach to Modulator Therapy
Dr. Guimbellot emphasizes that the study's goal is to shift the paradigm of CF care by improving the understanding of optimal drug concentration and dosing for each patient's lung function and tolerance of therapy. The ultimate aim is to transition the standard of care to a truly personalized and patient-centered approach to modulator therapy.
