MSUD is typically diagnosed at birth via newborn screening and incidence is estimated at 1 in 185,000 people worldwide and 1 in 220,000 people in the United States. Although metabolic management of the disease is possible via a highly restrictive diet, the outcome is unpredictable, and a significant portion of affected individuals are mentally impaired or experience neurological complications. The most severe presentation of MSUD, known as “classic” MSUD, accounts for 80% of cases and can result in neonatal onset with encephalopathy and coma. Left untreated, this can result in neurological damage, mental disability, coma, or death. MSUD is a rare inherited disorder caused by a deficiency of branched-chain alpha-keto acid dehydrogenase complex, resulting in elevated blood levels of the branched-chain amino acids (BCAA) leucine, valine, and isoleucine, as well as the associated branched-chain ketoacids (BCKA) in a patient’s blood. 6 The results suggested that sodium phenylbutyrate could be safely administered in combination with emergency protocol using other active pharmaceuticals and may provide additional clinical benefit beyond emergency protocol alone. In November 2020, study results evaluating the effect of sodium phenylbutyrate in the management of acute metabolic decompensation in pediatric MSUD patients (n=10) were published by investigators from Istanbul University-Cerrahpasa Medical Faculty in the peer-reviewed Journal of Pediatric Endocrinology and Metabolism showing a significant reduction in leucine levels in MSUD patients experiencing an acute attack. The investigators found that sodium phenylbutyrate, when dosed over three days, showed a statistically significant reduction of leucine in all three healthy subjects and in three out of the five MSUD patients who participated in the trial. 2īased on this clinical observation, investigators at Baylor College of Medicine explored the potential of sodium phenylbutyrate treatment to lower BCAA and corresponding branched-chain α-ketoacid (BCKA) levels in both healthy subjects and patients with MSUD. 1,2,3,4 Analysis of data from a longitudinal multicenter study of 553 UCD patients treated with sodium phenylbutyrate demonstrated that sodium phenylbutyrate decreased plasma BCAA in patients with UCDs and could serve as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. Multiple investigational trials evaluating sodium phenylbutyrate in urea cycle disorder (UCD) patients suggest treatment with sodium phenylbutyrate is associated with selective reduction in BCAA despite adequate dietary protein intake. The proposed initial Phase 2a, open-label dose-ranging trial is designed to evaluate the effect of different doses of ACER-001 (sodium phenylbutyrate) on blood leucine and other branched-chain amino acid (BCAA) levels in MSUD patients. We look forward to the initiation of this investigational trial and learning more about ACER-001’s potential to reduce branched-chain amino acids, and specifically leucine levels, in MSUD patients.” “Even with strict dietary management, people with MSUD still remain at serious risk for a wide range of life-threatening complications. “We are very pleased to expand ACER-001’s clinical development into a second rare disease, and one for which there are currently no approved pharmacologic therapies,” said Adrian Quartel, MD, FFPM, Chief Medical Officer of Acer. Currently, the only treatment option for patients with MSUD is a life-long, protein-restricted diet. Left untreated, MSUD leads to elevated plasma concentrations of these amino acids, which can lead to chronic and acute neurological damage, ranging from developmental delays in children, seizures, cognitive challenges and in some cases death. MSUD is a rare, life-threatening metabolic disorder caused by a deficiency in an enzyme complex that metabolizes branched chain ketoacids, the breakdown products of the three branched-chain amino acids (BCAAs), leucine, valine, and isoleucine. Food and Drug Administration (FDA) to evaluate the efficacy and safety of ACER-001 (sodium phenylbutyrate) for the potential treatment of patients with maple syrup urine disease (MSUD). (Nasdaq: ACER) (Acer) and its collaboration partner, RELIEF THERAPEUTICS Holding SA (SIX: RLF, OTCQB: RLFTF, RLFTY) (Relief), today announced the submission of an Investigational New Drug (IND) application to the U.S. NEWTON, MA and GENEVA, SWITZERLAND – J– Acer Therapeutics Inc. Phase 2a trial initiation planned for the first half of 2023 subject to IND clearance and available capital Acer Therapeutics and Relief Therapeutics Announce ACER-001 IND Submission for the Treatment of Maple Syrup Urine Disease
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