What are JAK2 inhibitors, and how do they work in treating myelofibrosis?

What are JAK2 inhibitors and how do they work in treating myelofibrosis?

You know colloquially we do call them JAK inhibitors. But for myeloproliferative neoplasms or MPNs, we think that the JAK2 form is the most important. JAK is a protein that has multiple shapes: JAK1, JAK2, JAK3. But in JAK2, the inhibition by some of these therapies decreases the inflammation for the MPN patients, contrasting with other diseases like autoimmune conditions and psoriasis, where JAK1 inhibition is really important. So to answer your question more directly, JAK2 in general leads to downstream activation of a very important pathway in myelofibrosis and other MPNs. This pathway is called the JAK/STAT signaling pathway. When we give a patient an oral form of a JAK2 inhibitor, we find that we can inhibit this pathway and decrease the downstream inflammation that's associated with the JAK/STAT pathway. This is very meaningful for patients actually, because it leads to two pretty profound results. Number one is that with the decrease in inflammation there, spleen size decreases and they feel better from typically a symptomatic spot immediately. Another advantage from the JAK2 inhibitors is that it decreases the symptoms that the patient may experience from the inflammation of myelofibrosis. And some of these symptoms can include fevers, night sweats, abnormal weight loss, among others.