Kristen Skvorak, Joyce Liu, Nikki Kruse, Roasa Mehmood, Subhamoy Das, Stephan Jenne, Chinping Chng, U Loi Lao, Da Duan, Jonathan Asfaha, Faye Du, Leann Teadt, Antionette Sero, Charlene Ching, James Riggins, Lianne Pope, Ping Yan, Harminder Mashiana, Moulay Hicham Alaoui Ismaili, Kerryn McCluskie, Gjalt Huisman, Adam P Silverman
Maple syrup urine disease (MSUD) is an inborn error of branched-chain amino acid metabolism affecting several thousand individuals worldwide. MSUD patients have elevated levels of plasma leucine and its metabolic product α-ketoisocaproate (KIC), which can lead to severe neurotoxicity, coma, and death. Patients must maintain a strict diet of protein restriction and medical formula, and periods of noncompliance or illness can lead to acute metabolic decompensation or cumulative neurological impairment. Given the lack of therapeutic options for MSUD patients, we sought to develop an oral enzyme therapy that can degrade leucine within the gastrointestinal tract prior to its systemic absorption and thus enable patients to maintain acceptable plasma leucine levels while broadening their access to natural protein...
November 2023: Journal of Inherited Metabolic Disease