Dalazatide (formerly known as ShK-186) is a first-in-class investigational drug designed to selectively target cells that cause autoimmune diseases such as lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, and multiple sclerosis (MS).
How dalazatide works
In MS, the immune system mistakenly attacks the myelin (a protective layer surrounding nerve fibers), leading to disrupted communication between nerve and muscle cells and eventually permanent nerve damage, resulting in severe neurodegenerative complications.
Dalazatide is a synthetic analog of a peptide extracted from the Caribbean sea anemone. It inhibits the Kv1.3 potassium channel and is an important new pharmaceutical target because of its expression on effector memory T-cells, a subset of the T-cell family that leads to inflammation and tissue damage in autoimmune diseases.
The Kv1.3 potassium channel is highly upregulated on effector memory T-cells, and is involved in regulating their calcium uptake. Signaling through calcium is essential to activate the effector memory T-cells. By blocking the Kv1.3 potassium channel, dalazatide blocks the activation of the effector memory T-cells, and is predicted to result in less nerve damage caused by the immune system, and reduce the symptoms of MS.
Dalazatide does not suppress other T-cell subtypes and therefore leaves the immune response intact. As a result, it is thought that dalazatide will not cause broad immune suppression or result in decreased immunity to infections.
Dalazatide in clinical trials
Preclinical trials with dalazatide using animal models of MS have shown promising results. For example, results published in the Journal of Pharmacology and Experimental Therapeutics showed that treatment with dalazatide significantly reduced the clinical score in a rat model of MS.
A Phase 1 trial (NCT02446340) assessing the safety and tolerability of dalazatide in 32 healthy volunteers was completed in 2014. These initial results showed good tolerability, no significant findings in medical and physical exams, and mild adverse events.
Additionally, a Phase 1b trial (NCT02435342) testing dalazatide in people with psoriasis completed in 2015 confirmed the clinical activity of the drug and showed it to be well tolerated; all participants completed the trial and only mild adverse events were recorded.