Encapsulated N-Acetylmannosamine or N-Acetylneuraminic Acid as a Therapeutic Agent for Increasing Sialylation in Certain Muscula

Description of Invention:
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.

Applications:

• 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.

Advantages:

• 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 Status:

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

Inventors:
Marjan Huizing (NHGRI)


Patent Status:
HHS, Reference No. E-270-2011/0
US, Application No. 61/531,934 filed 07 Sep 2011


Relevant Publication:

1. Galeano B, et al. [ PMID 17549255 ]
2. Nemunaitis G, et al. [ PMID 21517694 ]
3. Kakani S, et al. The Gne M712T mouse as a model for human glomerulopathy. Am J Pathol., in press (Dec 2011) (available online in Feb 2012)

For Licensing Information Please Contact:
Tara Kirby Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: tk200h@nih.gov
Phone: 301-435-4426
Fax: 301-402-0220


Ref No: 2359

Updated: 02/2012