Yumanity Therapeutics announced the results of a study that demonstrate in vivo efficacy including increased median overall survival of YTX-7739 in a mouse model for glioblastoma multiforme. The study was conducted by researchers at the Massachusetts General Hospital and is being presented virtually at the Society for NeuroOncology/National Cancer Institute Joint Symposium: Targeting CNS Tumor Metabolism. YTX-7739 is currently in clinical development by Yumanity Therapeutics as a potential treatment for Parkinson’s disease. The research entitled, Targeting Fatty Acid Biosynthesis in Glioblastoma, was conducted in the laboratory of Christian E. Badr, Ph.D., of Massachusetts General Hospital and presented by Katharina M. Eyme. They had recently shown that GBM cancer stem cells are highly susceptible to pharmacological permutation of stearoyl-CoA desaturase (SCD). SCD inhibition in these cells leads to the toxic accumulation of saturated fatty acids and impairs DNA damage repair, hence sensitizing cells to DNA-damaging agents such as temozolomide (TMZ). In this study, YTX-7739, an orally available SCD inhibitor that is in clinical development for the treatment of Parkinson’s disease, was administered either alone or with TMZ to mice following intracranial implantation of GBM cells. The investigators found that YTX-7739, and a second SCD inhibitor in development by Yumanity, YTX-9184, each increased median survival as monotherapy and was synergistic with TMZ in both aggressive and slow growing tumors. The authors concluded that SCD inhibition could possibly be a viable approach to improving treatment of GBM in humans, as either single or adjunctive therapy. YTX-7739 is Yumanity Therapeutics’ proprietary lead small molecule investigational therapy designed to penetrate the blood-brain barrier and inhibit the activity of a novel target, stearoyl-CoA desaturase (SCD). SCD appears to play an important and previously unrecognized role in mitigating neurotoxicity arising from the effects of pathogenic alpha-synuclein protein aggregation and accumulation, which ultimately results in the death of neurons and the subsequent dysregulation of movement and cognition that afflicts patients living with these diseases. Through inhibition of SCD, YTX-7739 modulates an upstream process in the alpha-synuclein pathological cascade and has been shown to rescue or prevent toxicity in cellular and preclinical models. The company is assessing the potential utility of YTX-7739 as a disease modifying therapy for Parkinson’s disease. SCD is an enzyme that catalyzes fatty acid desaturation, the products of which are incorporated into phospholipids, triglycerides, or cholesterol esters. These lipid-related molecules regulate multiple diverse cellular properties and processes, including membrane structure and function, vesicle trafficking, intracellular signaling and inflammation. SCD expression is regulated by a transcription factor known as SREBF1, which has been identified in human genome-wide association studies as a risk factor for Parkinson’s disease. In preclinical models, SCD inhibition appears to normalize the dynamic interaction of pathological alpha-synuclein with membranes, which improves neuronal function and reduces toxicity, leading to enhanced neuronal survival. Alpha-synuclein-dependent disruption of membrane-related biological pathways, such as vesicle trafficking, is closely linked to the formation of Lewy body protein/membrane aggregations, a hallmark pathological feature of Parkinson’s disease.