EE Attends the 18th ECFS Basic Science Conference
Last month, Emily’s Entourage’s (EE) Chief Scientific Officer, Chandra Ghose, PhD, traveled to attend the 18th European Cystic Fibrosis Society (ECFS) Basic Science Conference, held from March 29 to April 1, 2023 in Dubrovnik, Croatia. Bringing together scientists from around the world, the conference provides a platform for highly interactive and in-depth discussions on cutting-edge science in a collaborative, intimate setting.
Dr. Ghose attended the conference to hear about the latest research, meet new and prospective scientific collaborators, and represent EE and the final 10% of the CF community that does not benefit from existing mutation-targeted therapies in this international environment.
With that in mind, we’re excited to share some of Chandra’s takeaways for the final 10% from the conference with you!
Gene-based therapeutic approaches that have the potential to address the needs of the final 10% of people with CF were a major focal point of this year’s conference. Talks by Drs. Marianne Carlon, PhD, from KU Leuven, Olivier Tabary, PhD, from the French Institute of Health and Medical Research (Inserm) and Graham Hart, PhD, from University College London highlighted promising results of gene-based therapy approaches.
- Dr. Carlon’s presentation highlighted the exciting possibility of using base and prime editing (PE) to correct splicing and nonsense mutations of CFTR. Dr. Carlon, a 2022 EE grant recipient, is working to develop a PE strategy for the drug-refractory CFTR mutation N1303K, one of the common, severe, disease-causing mutations in the CFTR gene which causes gating abnormalities of the CFTR protein. Her work aims to identify the optimal gene editing system to balance efficiency with safety and ease of delivery. This represents a novel approach that could play an important role in reaching people with CF who do not benefit from currently available therapies.
- Dr. Tabary’s strategy uses antisense oligonucleotides (ASOs) targeting TMEM16A, an ion channel that could play a part in regulating salt chloride balance in the cells, to potentially treat all CFTR mutations. Although CFTR is the main chloride channel in the lungs, others including TMEM16A play a role in compensating for the deficiency of CFTR. He highlighted in vivo studies in mice that resulted in weight gain and survival to nearly 200 days, demonstrating early but promising data for this treatment approach.
- Dr. Hart’s presentation described his lab’s work utilizing messenger RNA (mRNA) packaged in anionic lipid nanoparticles (LNPs). This technology is exciting for several reasons. mRNA-based therapy aims to deliver the correct genetic instructions to cells, allowing the person’s own cells to make functional CFTR protein regardless of their CF mutations. These therapies are delivered inside of powerful LNPs that have the potential to break through the thick mucus layer on the lungs of people with CF.
These talks highlighted the advances that have been made in recent years that are relevant (and exciting!) for the final 10%. In addition, significant advances in gene therapy have led to FDA-approved treatments for a number of other diseases, including inherited retinal disorder and spinal muscular atrophy (SMA). Advances in other diseases propel the whole field forward with significant implications for CF as well. With so much excitement around the potential of gene-based approaches, we were thrilled to hear these updates are demonstrating real, tangible progress in CF.
Despite the promise of these gene-based therapies, delivery remains a significant obstacle, as discussed by Dr. Marie Egan, MD, from Yale University in her keynote talk and by Dr. Daniella Ishimaru, PhD, from Recode Therapeutics. Both speakers provided updates on the progress in developing effective delivery methods for gene-based therapies. Dr. Egan shared her lab’s work on peptide nucleic acid (PNA) delivery platforms. PNAs are synthetic DNA-like molecules that bind even more strongly to nucleic acids and are not broken down in the body by enzymes that target DNA or RNA. These qualities make them potent therapeutics aimed at silencing or editing genes. Dr. Egan’s studies in mice resulted in partial gain of CFTR function, showing early promise.
Dr. Ishimaru presented exciting new data demonstrating the ability to rescue CFTR function by delivering mRNA packaged in LNPs to primary human bronchial epithelial cells derived from patients with different CFTR genotypes. Both of these presentations highlight the progress being made as research moves from the bench in cells (in vitro) to animals (in vivo) and then onto the preclinical development stage, and ultimately, to people with CF
Another significant highlight of the conference was the presentation by Dr. Justin Ideozu, PhD from AbbVie on the pan-ethnic characterization of CFTR variants beyond those commonly associated with people of European ancestry. The study revealed that over 4,000 CFTR variants were detected, many of which have never been reported in CF, in people of African, American, European, Middle Eastern, Central South Asian, and East Asian ancestry. This finding shows that there are significantly more people with CF around the world that have not been diagnosed, and do not benefit from currently approved therapies.
The determination of the scientists and physicians leading innovative research was front and center at ECFS. Reinvigorated by these updates and always science and data-focused, EE remains committed to advancing scientific collaboration and research and drug development to make these therapeutics a reality as soon as possible.