Grants Awarded

Principal Investigator
Kimberly Risma, MD, PhD
Cincinnati Children’s Hospital Medical Center – Cincinnati, Ohio USA

Date of Award
December 2011

Amount of Award
$50,000

Layperson Summary
The immune system utilizes white blood cells to kill virally-infected cells and tumor cells by cells called natural
killer cells and killer T cells. These cells secrete two proteins that work together to eliminate abnormal cells in
the body: perforin and granzyme B. Perforin “delivers” the lethal weapon, granzyme B, which kills the targeted
cell. When perforin function is defective due to a mutation in the gene, affected children are at risk for death
from a severe inflammatory disease called type 2 hemophagocytic lymphohistiocytosis (FHL2). Currently the
only treatment for FHL2 is bone marrow transplantation, which is curative but associated with significant
complications before the new bone marrow begins to work. It would be ideal to replace the perforin gene in a
patient’s own cells to restore the body’s ability to restore killer cell function. This approach is called gene
therapy and has been effective in other immunodeficiencies. This proposal seeks to develop preliminary data
to establish the feasibility of gene therapy for perforin deficiency.

Twelve Month Report