Douglas V. Faller, MD, PhD, Grunebaum Professor for Cancer Research and professor of medicine, pediatrics, biochemistry, microbiology, pathology and laboratory medicine; vice-chairman, Division of Medicine; and director of the Cancer Center at Boston University School of Medicine (BUSM), recently was awarded the Marta Marx Award from the Scleroderma Foundation for receiving the top score of all proposals reviewed by the scientific peer-review committee. The award includes a two-year $150,000 grant for his project “PKCs Inhibitors as Targeted Therapeutics for Systemic Sclerosis.”
Scleroderma, or systemic sclerosis (SSc), is a chronic connective tissue disease generally classified as one of the autoimmune rheumatic diseases. Scleroderma is a disease that involves the buildup of scar-like tissue in the skin. It also damages the cells the line the walls of the small arteries. The cause of scleroderma is unknown.
The hallmark features of SSc include vascular damage, immune dysfunction and extensive skin and organ fibrosis. According to Faller, significant strides have been made in understanding the development of SSc and identifying potential therapeutic targets, including a central role for transforming growth factor (TGFb) signaling. “The novel Protein Kinase C isozyme (PKCd) plays a key role in the occurrence of fibrosis and vasculopathy in SSc. My colleague, professor Maria Trojanowska, director of the Arthritis Center has shown that in SSc fibroblasts, PKCd is activated, and fibrosis induced by TGFb is dependent upon PKCd. The TGFb/PKCd pathway is also involved in the fibrotic pathology of multiple other fibrotic diseases. Thus, blocking the TGFb/PKCd pathway could be an attractive therapeutic approach for both the vasculopathy and the fibrosis of SSc,” explained Faller, who also is vice chairman of the Cancer Research Center at Boston Medical Center. “We have now developed novel small molecule drugs to block this pathway,” he added.
Faller believes that a specific small-molecule inhibitor of PKCd would ameliorate the fibrosis and vascular pathology induced by TGFb and other inflammatory mediators in models of scleroderma, and represents a new therapeutic approach to this disease. “Since therapeutic options for SSc are limited, the development of such novel and targeted treatments is of paramount importance,” said Faller.