NU 2022-093

INVENTORS  

• Peng Ji*
• Kehan Ren
• Yang Mei

SHORT DESCRIPTION
A method of inhibiting progression of high-risk myelodysplastic syndrome (MDS) or low blast count acute myeloid leukemia (AML) using an inhibitor of IL6 signaling.

BACKGROUND
Approximately 20,000 people in the US are diagnosed with myelodysplastic syndrome (MDS) each year. MDS is an age-related disease with a median age of diagnosis of 71 years old. Patients with high-risk MDS have an increased risk of developing acute myeloid leukemia (AML) that comes with a poor prognosis and limited treatment options. Allogeneic stem cell transplantation (ASCT) is the only curative treatment option for high-risk patients, but many patients are ineligible due to age limitation and potential complications. The current standard of care for these patients is therapy with hypomethylating agents (HMAs); however, disease eventually becomes drug resistant. Thus, there is a need for more effective and potentially curative treatment methods for high-risk MDS patients.

ABSTRACT
It is known that MDS cells depend on IL-6 signaling for survival, proliferation, and progression. For the first time, Northwestern researchers have shown anti-IL6 signaling therapies presents a promising treatment method for patients with poor response to traditional HMA-based therapies. Specifically, they showed that treating MDS cells from patients with the IL-6 pathway inhibitor tocilizumab, led to reduced proliferation and cell death. This mechanism provides a more effective treatment method for patients with poor response to traditional HMA-based therapies. Additionally, it has less adverse effects than chemotherapy, making it a more tolerable treatment method for elderly patients. Overall, this invention has the potential to resolve the unmet medical needs for the treatment of high-risk MDS to prevent the progression to AML. 

APPLICATIONS

• Treatment of patients with high-risk MDS to prevent disease progression. 
• Treatment of patients with AML that developed from MDS. 

ADVANTAGES

• Less adverse effects compared to chemotherapy. 
• Effective for elderly patients who are not eligible for chemotherapy and/or bone marrow transplantation. 
• Alternative therapy for patients with poor response to HMA therapies. 

PUBLICATION
Mei Y, Ren K, Liu Y, Ma A, Xia Z, Han X, Li E, Tariq H, Bao H, Xie X, Zou C, Zhang D, Li Z, Dong L, Verma A, Lu X, Abaza Y, Altman J, Sukhanova M, Yang J, Ji P. Bone marrow-confined IL-6 signaling mediates the progression of myelodysplastic syndromes to acute myeloid leukemia. J Clin Invest. 2022;132(17):e152673. 

IP STATUS 
US Patent application (18/347,541) filed. 

Tocilizumab (TCZ) reduces cell proliferation and colony formation in MDS patient cells.