The first John W. Walsh Translational Research award has been granted to Joseph Kaserman – MD, instructor of medicine at Boston University School of Medicine (BUSM) and a physician in Pulmonary, Allergy, Sleep and Critical Care Medicine at Boston Medical Center.
The award was granted by the Alpha-1 Foundation. Alpha-1 Antitrypsin Deficiency (Alpha-1) is a genetic (inherited) condition – it is passed from parents to their children through their genes. Alpha-1 may result in serious lung disease in adults and/or liver disease at any age.
Kaserman will be using the award to address a long outstanding question in the field of whether Alpha-1 carriers (these are individuals who have one normal Alpha1 gene (M) and one mutated gene (Z) have an increased risk of developing liver disease. As up to 2% of the U.S. population could be an Alpha-1 carrier there remains a critical need to address this important question.
For his research Kaserman will be working with specialized adult stem cells named induced pluripotent stem cells (iPSCs), which are stem cells that have been created from patients with Alpha-1 Antitrypsin Deficiency. Importantly, iPSCs contain all the genetic information of the original patient, and provide the ability to compare cells from patients that have the same mutation but different disease severity, i.e. patients who have the Z-mutation with or without liver damage.
To understand the risk associated with having either one or two Z genes, Kaserman will take advantage of a technology known as CRISPR that allows for altering or “editing” the DNA of cells including iPSCs that he has made from Alpha-1 patients. Using this approach, Kaserman will be able to conduct experiments comparing “ZZ”, “MZ”, and “MM” cells that all come from the same individual and thus are genetically identical, varying only at the site of the Alpha-1 Antitrypsin gene that has been edited.
Kaserman will then create liver cells from these iPSCs and examine whether MZ cells accumulate more misfolded AAT protein or are more susceptible to injury than MM cells. As there remain no approved therapies for Alpha-1 liver disease this study will also test new therapeutic agents targeting the mutated Z-protein within cells to see if this will protect the susceptible liver cells from injury.
Overall this study has the potential to not only address the concerns of many Alpha-1 carriers about their risk of developing liver disease, but also to find new treatments for Alpha-1 related liver disease helping both Alpha-1 carriers as well as Alpha-1 patients.
The award consists of up to a total of $225,000 ($75,000/year) over three years. The Alpha-1 Foundation, the Center for Regenerative Medicine of Boston University and Boston Medical Center, congratulate Kaserman, and look forward to the research findings, which will surely bring us closer to finding the cure for Alpha-1 Antitrypsin Deficiency (Alpha-1).
Back in October 2016, in recognition of John Walsh’s many contributions, Mark Brantly, MD, announced a $225,000 gift from himself and his wife Judy Lew, MD, to the Foundation during the Alpha-1 Donor Recognition Dinner. The gift was intended to be the first to establish the John W. Walsh Translational Research Award.