What is Menin?
Menin is a central player in the human cell that brings other proteins together to regulate the expression of genes that are key to cell growth, cell differentiation or cell senescence. Menin is a key scaffold protein that functionally crosstalks with various partners to regulate gene transcription and interplay with multiple signaling pathways. Menin is an important transcriptional regulator. It also impacts major processes such as cell cycle control, apoptosis and DNA damage repair. The MEN 1 gene and its associated protein, menin, was identified and named in 1997 by two research groups, the National Institute of Health group and the European MEN1 Consortium (Chandrasekharappa et al. 1997)
Critical Protein in Diabetes
Loss of functional beta cell mass is a core component of type 2 diabetes — mediated by metabolic dysfunction. Beta cells in the pancreas synthesize and secrete insulin, a hormone that helps the body use glucose for energy and controls blood glucose levels. Diabetes diminishes beta-cell mass and function, leading to insufficient insulin secretion and hyperglycemia. Menin is thought to act as a brake on beta-cell turnover and growth, and menin inhibition may lead to the regeneration of normal, healthy beta cells. Biomea is exploring the potential for BMF-219-mediated menin inhibition as a viable therapeutic approach to permanently halt or reverse the progression of type 2 diabetes.
Critical Protein in Oncology
Genetically defined leukemias, such as MLL-r, and other cancers show the potential for dependence on menin. MLL-r leukemias are characterized by MLL gene (also known as KMT2A) translocation abnormalities. These abnormalities result in the formation of fusion genes encoding fusion proteins comprising MLL1 and a fusion partner domain. The interaction of these fusion proteins with menin drives the expression of downstream target genes (such as HOXA9 and MEIS1), triggering leukemic cell proliferation. Preventing the MLL proteins from binding to menin has been shown to abolish the oncogenic effects in vitro and in vivo. Approximately 20,000 and 6,000 patients in the United States are diagnosed annually with acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL), respectively. Given the clear involvement of MLL and NPM1 in acute leukemias, and the poor clinical outcomes provided by available treatments, we believe a new treatment that can inhibit the function of both targets by disrupting or preventing interactions with menin could address this unmet need.
