Alpha-Man - Clinical development of enzyme replacement therapy
Project start: October 2010. Project completion: March 2014.
Lysosomal storage diseasesLysosomes are enzyme-containing organelles in the cell. The enzymes contribute to the degradation of different components of the cell, e.g. proteins, carbohydrates and lipids. Are one, or more, of these lysosomal enzymes defective, it will result in accumulation of un-wanted molecules and a number of serious illnesses referred to as ”lysosomal storage diseases” (LSDs). Today 50 different lysosomal diseases are known, where one of these are alpha-Mannosidosis.
Alpha-Mannosidosis The genetic disease alpha-Mannosidosis is caused by defect in the enzyme lysosomal acid alpha-Mannosidase (LAMAN). The disease belongs to the category of “orphan” diseases as it is a rare disease only affecting around 500 people worldwide. It is, however, a serious disease as it results in several severe symptoms as for example skeletal changes and bone deformation, mental retardation and hearing loss. Many patients affected by the disease die during early childhood.
The goal To date, no real treatment for Alpha-Mannosidosis is available. The best treatment option for would be Enzyme Replacement Therapy (ERT) where a recombinant version of the defect enzyme is injected to degrade the accumulated oligosaccharides. The goal of the Alpha-Man project is to develop the first ERT-based treatment of alpha-Mannosidosis. During the Alpha-Man project the enzyme Alpha-Mannosidase will be taken through preclinical development and through phase I, II and III clinical trials.
Danish Technological Institute (DTI), section for Medical Biotechnology, contributes to the clinical studies by analyzing serum and cerebrospinal fluid (CSF) from different alpha-Mannosidosis patients, before and during treatment (6 month and 12 month). The amount of accumulated mannose in the patient samples will be determined and quantified. Detection and quantification is performed on a HPLC and the analysis verified using a LTQ Orbitrap Velos mass spectrometer. The amount of accumulated mannose will be compared for treated and non-treated patients
- Christian-Albrechts-University Kiel, Germany
- Zymenex, Denmark
- Copenhagen University, Denmark
- Katholieke University Leuven (K.U.Leuven), Belgium
- Manchester Children´s University Hospital, United Kingdom
- Johannes-Gutenberg-University Mainz, Germany
- Hospices Civils de Lyon, France
- University Tromsoe, Norway
- The Children´s Memorial Health Institute Warsaw, Poland
- Larix, Denmark
- Unilabs, Denmark
The project is funded by the European Commission under the 7th Framework Program.