Tom E. Howard, MD, PhD, on a Gene Editing Approach to Treating Hemophilia A

This is the second part of an interview with Tom E. Howard, MD, PhD. For the first part, click here.

“Our ultimate goal is to have a cell therapy that utilizes our gene editing-based therapeutic, to be able to get patients their own cells back making high enough levels of their own FVIII protein where they don't have to get treated again or maybe only have to get treated once every year or 2 years, instead of 3 times a week having to inject themselves with the protein...”

Currently, one of the main treatment options for patients with hemophilia A is receiving exogenous infusions of the disease-targeted protein, Factor VIII (FVIII), multiple times per week. Although this option is effective for some patients, other patients may develop an immune response to these exogenous proteins in the form of FVIII inhibitors, limiting their ability benefit from or continue to receive the treatment. Tom E. Howard, MD, PhD, a clinical professor in the Department of Human Genetics at University of Texas Rio Grande, and his colleagues, have been investigating this issue for many years, and recently presented some of their findings at the the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California.^1,2 Furthermore, they are now working on a gene editing approach to treating hemophilia A based on this research that is intended to provide patients with the ability to make their own FVIII protein without triggering an immune response.

CGTLive™ spoke with Howard at the conference to learn more. After discussing the main findings of his and his colleagues’ research, Howard spoke about the novel gene editing approach, which is being worked on by a subsidiary of a company called Haplomics that they founded. Howard noted that patients with more mutations in their FVIII gene, with resulting proteins that are very different from wild type FVIII, have the highest risk for an immune response to exogenous or wild type FVIII. As such, the gene editing approach will seek to analyze patients’ own mutations and apply a personalized genetic edit that will allow the patient’s own cells to produce a functional FVIII protein, with minimized differences from the mutated protein in order to reduce the risk of an immune response.

REFERENCES
1. Bouls R, AlmeidaMA, DiegoVP, et al. Gene-centric association scans of pleiotropic immune-mediated disease genes in the PATH study identify novel determinants of Factor VIII inhibitor risk in hemophilia-A patients and confirm race as an independent predictor. Presented at: ASH 2023 Annual Meeting & Exposition. December 9-12; San Diego, CA. Abstract #1246
2. Ibarra P, Almeida MA, Diego VP, et al. Results from an association-scan of the extended MHC-Class-II region using novel association-based statistical methods establish that DQ allotypes and race independently influence the risk of factor VIII inhibitor development in hemophilia-A patients. Presented at: ASH 2023 Annual Meeting & Exposition. December 9-12; San Diego, CA. Abstract #1247