Encapsulated N-Acetylmannosamine or N-Acetylneuraminic Acid as a Therapeutic Agent for Increasing Sialylation in Certain Muscular Atrophies, Kidney Disorders, Cancers or Poor Immune Function


N-acetylmannosamine is a precursor for the synthesis of sugar molecules known as sialic acids, which play an important role in specific biological processes such as cellular adhesion, cellular communication and signal transduction. Lack of sialic acids also plays a crucial role in disease processes such as inflammation, immune responses, as well as certain muscular atrophies (including hereditary inclusion body myopathy (HIBM) and distal myopathy with rimmed vacuoles (DMRV or Nonaka myopathy)), certain kidney disorders with proteinuria and hematuria (including minimal change nephrosis and focal segmental glomerulosclerosis), and certain cancers (including bladder cancer and myeloid leukemia).

This technology relates to methods of administering liposome-encapsulated N-acetylmannosamine, N-acetylneuraminic acid, or their derivatives to treat human disorders of hyposialylation (by increasing sialic acid production in patients who are deficient in that sugar molecule). Liposome-encapsulated delivery of these monosaccharides enhances successful systemic delivery, including to the central nervous system (crossing the blood-brain barrier), and liposome encapsulation protects against gastrointestinal tract degradation.

Potential Commercial Applications: Competitive Advantages:
  • Treatment of rare diseases such as HIBM and Nonaka myopathy (or DMRV).
  • Treatment of kidney conditions involving sialic acid deficiencies, resulting in proteinuria and hematuria.
  • Treatment of other diseases involving sialic acid deficiencies.
  • Use as immune stimulant since adequate sialic acid is important for robust immune function.
 
  • N-acetylmannosamine is the only uncharged sugar in the sialic acid biosynthesis pathway (thus making it easier to deliver than charged sugars) and is located after the rate-limiting step.
  • N-acetyl mannosamine and N-acetylneuraminic acid have been shown to rescue hyposialylation in mouse models of HIBM.
  • Encapsulated N-acetylmannosamine or N-acetylneuraminic acid crosses the blood-brain barrier and prevents gastrointestinal tract degradation more efficiently than unencapsulated drug.


Development Stage:
  • Pre-clinical
  • In vitro data available
  • In vivo data available (animal)


Inventors:

Marjan Huizing (NHGRI)  ➽ more inventions...


Intellectual Property:
US Application No. 61/531,934
US Application No. 13/605,946

Publications:
Galeano B, et al. PMID 17549255
Nemunaitis G, et al. PMID 21517694
Kakani S, et al. PMID 22322304

Licensing Contact:
Eggerton Campbell, Ph.D.
Email: eggerton.campbell@nih.gov
Phone: 301-402-1648

OTT Reference No: E-270-2011-0
Updated: Sep 21, 2015