ACER-001 for Maple Syrup Urine Disease (MSUD)


ACER-001 is a fully taste-masked, immediate-release formulation of sodium phenylbutyrate (NaPB) developed using a microencapsulation process.1 Treatment with NaPB is also currently being studied as a treatment for people with maple syrup urine disease (MSUD).

NaPB is approved for people with urea cycle disorders (UCDs) to control their ammonia levels in conjunction with a restricted diet. People with UCDs who are treated with NaPB have been found to have induced branched-chain amino acid (BCAA) deficiency, despite adequate dietary protein intake.2

Based on this clinical observation, investigators at Baylor College of Medicine (“BCM”) explored the potential of NaPB treatment to lower BCAA and their corresponding BCKA in patients with MSUD, a disease where BCAA/BCKA levels are significantly elevated. The investigators found that BCAA and BCKA were both significantly reduced following NaPB therapy in control subjects and in patients with MSUD, although there was no simple correlation between the patients’ levels of residual enzymatic activity with the response of plasma BCAA and their BCKA to NaPB.3 NaPB demonstrated 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. The reduction in leucine, the most toxic of the BCAAs, in the three responsive MSUD patients ranged between 28-34%, which is considered by clinicians to be a meaningful response.

Investigators at BCM further explored the mechanistic rationale why NaPB lowered BCAA/BCKA levels. NaPB was found to be an allosteric inhibitor of the branched-chain keto acid dehydrogenase complex kinase (BCKD-kinase), and enzyme that regulates the activity of the branched-chain keto acid dehydrogenase complex (BCKDC) enzyme that is responsible for the normal metabolism of BCKAs.3 By inhibiting the BCKD-kinase, the BCKDC is constitutively activated, thus the increased activity results in a reduction in the plasma levels of BCAA and BCKA in all people, including those with MSUD,3 suggesting that NaPB may be an effective treatment for people with MSUD, who experience elevated BCAA levels.3,4

ACER-001 was granted orphan drug designation as a potential treatment for MSUD in 2014. We intend to seek FDA approval to market ACER-001 for the treatment of MSUD in the United States by submitting a 505(b)(2) NDA using data from the reference listed drug’s NDA while supplementing the data with additional pharmokinetic, pharmodynamic, efficacy and safety data specifically in the MSUD population.


  1. Shchelochkov OA, et al: Barriers to drug adherence in the treatment of urea cycle disorders: Assessment of patient, caregiver and provider perspectives. Mol Genet Metab. 2016;8:43-47.
  2. Scaglia F, et al: Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients. Mol Genet Metab. 2004;81(Suppl 1):S79-S85.
  3. Brunetti-Pierri N,et al. Phenylbutyrate therapy for maple syrup urine disease. Hum Mol Genet. 2010;19:631-640.
  4. Burrage LC, et al. Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders. Human Molecular Genetics 2014;23:R1-R8.