The researchers at Scripps Research and Calibr, its drug development subsidiary, have recently made an exciting discovery that has the potential to revolutionize the treatment of severe illnesses such as obesity, type 2 diabetes, and cardiovascular disease. They were able to use a cutting-edge drug discovery technology to convert white fat cells, also known as "bad" fat, into brown fat cells, also known as "good" fat, which is a potential solution to the metabolic conditions mentioned above.
How Metabolite Therapy Helps?
Metabolic diseases result from an imbalance in energy homeostasis and are caused by the body taking in more energy than it expends. The goal of therapy for these diseases is to convert white fat cells into brown fat cells, which dissolve stored energy into heat, helping to bring the body back into balance.
Taking this into account, the team at Scripp’s made use of Calibr's ReFRAME drug-repurposing collection and high-throughput screening to identify zafirlukast. Zafirlukast is a drug that is approved by the FDA for treating asthma, which was found to have the ability to convert white adipocytes into brown adipocytes.
The Solution Has Been Found But Its Increased Doses are Highly Toxic; What to Do?
However, zafirlukast was found to be toxic at higher doses, which posed a problem for the researchers. In light of this, the team decided to partner with a group of metabolite experts to find a metabolite that could provide the same effect without the side effects. To this end, they employed Drug-Initiated Activity Metabolomics (DIAM) screening to go through thousands of molecules and identify specific metabolites that could be used as potential therapeutics. This screening led the researchers to myristoylglycine, an endogenous metabolite that was found to be capable of converting white fat cells into brown fat cells without causing any harm to the cells.
Finally, the Breakthrough!
The discovery of myristoylglycine as a potential treatment for severe diseases such as obesity, type 2 diabetes, and cardiovascular disease is an exciting development in the world of medicine. The team at Scripps Research and Calibr have demonstrated the power of collaboration and innovation in the field of drug discovery and hope that their work will lead to new and effective treatments for those who are suffering from these conditions.
This novel drug discovery process has the potential to uncover numerous other potential therapies due to the body's ability to make its own endogenous metabolites that can have the same impact as a drug but with fewer side effects. The recent FDA approval of Relyvrio, a combination of two endogenous metabolites for the treatment of ALS, supports the promise of this approach.
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