An Open Label Phase 2 Study of ManNAc in Subjects With GNE Myopathy

• Subject is age 18-60 years, inclusive, and of either gender.
• Subject has a diagnosis of GNE myopathy based upon a consistent clinical course and identification of two GNE gene mutations.
• Subject must be willing to stop any treatment with ManNAc, sialic acid, intravenous immunoglobulin (IVIG), and/or other supplements containing sialic acid (e.g. St. John s wort, sialyllactose) 90 days prior to dosing and remain off such treatment for the duration of the trial.
• Subjects must have a body mass index (BMI) between 18 and 30 kg/m2, with a bodyweight of >50 kg.

• Subjects must have 20-75% of predicted strength measured by QMA at baseline on at least one of the following: 1) ankle dorsiflexion, 2) knee flexion, 3) hip extension, 4) grip, 5) elbow flexion, shoulder abduction

  • 20-75% of predicted strength measures by OMA at baseline, or
  • If predicted muscle strength above 75%, a documented change of at least 10% per year.
• Subject has the ability to travel to the NIH Clinical Center for admissions.
• Subject has an INR less than or equal to 1.5 and must have stopped warfarin and other anticoagulants 2 weeks prior and after muscle biopsy procedures. Aspirin and clopidogrel should be stopped 3 days and 5 days before the procedure, respectively.
• Subject must be able to comply with requirements of the protocol, including blood collection, drug administration, muscle MRI/MRS, muscle biopsy and muscle strength assessments.
• If a woman of reproductive age, subject must be willing to use an effective method of contraception for the duration of the trial.
• Subject must be able to provide informed consent.

EXCLUSION CRITERIA:

• Subject had a clinical significant infection or medical illness 30 days prior to the first protocol visit.
• Subject has a psychiatric illness or neurological disease that would interfere with the ability to comply with the requirements of this protocol. This includes, but is not limited to, uncontrolled/untreated psychotic depression, bipolar disorder, schizophrenia, substance abuse or dependence, antisocial personality disorder, panic disorder, or behavioral problems, which interfere with effective communication.
• Subject has hepatic laboratory parameters (AST, ALT, GGTP) or renal laboratory parameters (creatinine, BUN) greater than 3 times the upper limit of normal.
• Subject has known adverse reactions to anesthetic or sedatives utilized for muscle biopsy.
• Subject is anemic (defined as Hematocrit \<30%) or has platelets \<100,000 or white blood cell count less than 3,000.
• Subject shows evidence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, or gastrointestinal disease, or has a condition that requires immediate surgical intervention.
• Subject is pregnant or breastfeeding at any time during the study.
• Subject has received treatment with another investigational drug, investigational device, or approved therapy for investigational use less than 90 days prior to the first protocol visit.
• Subject has hypersensitivity to ManNAc or in the judgment of the investigator, has a condition that places the subject at increased risk for adverse effects.
• Subject has received ManNAc, sialic acid, intravenous immunoglobulin (IVIG), and/or other supplements containing sialic acid (e.g. St. John s wort, sialyllactose) less than 90 days prior to the first protocol visit.
• The presence of persistent diarrhea or malabsorption that could interfere with the subject s ability to absorb drugs or to tolerate ManNAc therapy.