A peptide isolated from the deadly venom of the sea anemone inspired the work of Dr. Christine Beeton at Baylor College of Medicine. Dr. Beeton created a synthetic analogue of the peptide, ShK-186, and is using it to develop a treatment for asthma. She, along with lead author Shyny Koshy, published work in The Journal of Biological Chemistry that details the effects of ShK-186: “We showed that ShK-186 treatment decreases inflammation and airway reactivity in a rat model of ovalbumin-induced asthma,” said Dr. Beeton in a news release.
Specifically, ShK-186 inhibits T-lymphocytes, or fully differentiated effector memory T-cells, that produce inflammatory cytokines that contribute to asthma pathogenesis. T-lymphocytes exclusively express Kv1.3 potassium channels in high numbers and depend on the channels to function. “Because of this, Kv1.3 channels are attractive targets for many autoimmune diseases. We studied its effect on allergic asthma because, while not autoimmune, it is a chronic inflammatory disease,” said Dr. Beeton. ShK-186 selectively blocks Kv1.3 and was used in the team’s study.
The team induced allergic asthma in rats and administered ShK-186. Then, after challenging rats with their allergen trigger, the researchers collected bronchial lavage fluid to analyze cell activation and cytokine expression. Fewer infiltrating lymphocytes, eosinophils, and neutrophils were present with ShK-186 treatment, and IL-4 and IL-5 levels were reduced.
In a patient-centric study, when the team collected T-lymphocytes from the lower airways of asthmatic patients, they found a significant proportion of cells expressed Kv1.3. ShK-186 attenuated the allergen-induced activation of these cells, as well. Dr. Beeton summarized, “We showed that by blocking Kv1.3, we limited the function of [effector memory T-cells] from patients with asthma and inhibited the T cells activity in a rat model, reducing inflammation and airway constriction.”
ShK-186 is patented to Seattle-based Kineta, Inc., which is a biotechnology company focusing on immune modulating drugs for the treatment of critical diseases. It is currently the experimental agent in a Phase 1c clinical trial for the treatment of psoriatic arthritis and is being investigated in a variety of preclinical studies on autoimmune diseases. There is still a ways to go before ShK-186 is marketed for asthma treatment, but Dr. Beeton believes the current data are promising.