New hope for patients suffering from rare genetic disease
Very few of us have heard of Alpha-Mannosidosis. However, this rare genetic disease has affected the lives of hundreds of families across Europe and the world. Its first symptoms appear in early childhood and include hearing loss, progressive facial and skeletal deformity, mental retardation, multiple organ abnormalities and recurrent infections, while, in its most aggressive form, it could lead to an early death.
© Joni Hofmann - fotolia
Due to its rarity, the private sector has shown limited interest in Alpha-Mannosidosis, and - as it is the case with most diseases of this type - there is no effective cure to date. But thanks to three successful research projects, co-funded by the European Union (EURAMAN, HUE-MAN and ALPHA-MAN), patients and their families can hope that a successful treatment will soon be within reach. The projects have built upon a collaborative network of European scientists, clinical doctors, and the pharmaceutical industry. The initial laboratory and clinical tests have been positive and encouraging.
Alpha-Mannosidosis is caused by a genetic deficiency in the waste management system of the patients cells. Due to this dysfunction, which, according to epidemiologists, occurs in approximately 1 of 500,000 live births, the body cannot process some sugars effectively. Hence, these sugars gradually accumulate inside the body cells, and, eventually, intoxicate and impair the cells. In aggressive cases of Alpha-Mannosidosis, the central nervous system is shutting down, and the patients die during the early years of their childhood. The reason for the inability to process sugars is the lack of the necessary lysosomal enzyme (alpha-mannosidase), a protein essential for the proper functioning of the cell.
The main objective of the EURAMAN, HUE-MAN and ALPHA-MAN projects (ALPHA-MAN is co-funded by the European Union with 5,900,000), is to treat the patient with the missing enzyme, by introducing a biotechnologically derived human enzyme ("rhLAMAN"), equivalent to the missing enzyme, into the bloodstream, which is then taken up by the cells and clears the sugars, hence countering the effects of the patients genetic mutation. The results of the pre-clinical trials of this so-called Enzyme Replacement Therapy were positive, and the teams engaged in the projects have moved on to the phase of clinical trials. Jens Fogh, CEO of the Danish biotech company Zymenex, which is producing rhLAMAN stated that the "the goal of the clinical trials is to make a future therapy available for all alpha-Mannosidosis patients.
In 2011, nine patients aged between 7 to 18 years were recruited to Phase 2 clinical trial from European hospitals and flown each week to Copenhagen, Denmark, to be treated at the Department of Clinical Genetics, Copenhagen University Hospital. Dr. Allan Meldgaard Lund, who is the Principal Investigator and treating physician of the patients, appeared very optimistic by the first results. His team observed marked improvements in the patients walking, their ability to climb stairs, their lung function and cognitive capacity. Scientists are convinced that, since children suffering from the condition are born healthy, an early diagnosis and start of the treatment could significantly improve their chances of survival as well as their quality of life.
Moreover, the projects have also had the goal of creating a database containing essential clinical observations and measurements, so as to enable a better understanding of an otherwise rare disease, by utilising the experience of researchers across Europe. The Alpha-Mannosidosis database that has been developed within the HUE-MAN and ALPHA-MAN projects is now available online.
Furthermore, scientists also hope to achieve a better understanding of the ways in which the missing enzyme enters the central system from the patients bloodstream and, ultimately, lay the foundation for the large scale production of an effective therapy. Paul Saftig, Director of the Biochemical Institute at the University of Kiel and coordinator of the HUE-MAN and ALPHA-MAN network feels that "understanding the mechanisms of the delivery of the drug to the brain will also be of general interest for many neurological diseases". Since Alpha-Mannosidosis belongs to a group of approximately 50 diseases, called lysosomal storage disorders, the conclusions of the EURAMAN, HUE-MAN and ALPHA-MAN projects could have a positive impact for thousands of patients suffering from similar conditions, including Gaucher, Fabry, and Pompe disease.
- Project acronym: ALPHA-MAN
- Participants: Germany (Coordinator), Denmark, Belgium, UK, France, Norway, Poland
- Project reference 261331
- Total cost: € 8 028 469
- EU contribution: € 5 887 150
- Duration: October 2010 - March 2014