Replacing an enzyme to control a very rare disease
Until recently, there was no treatment specific to alpha-mannosidosis, one of the many rare diseases that jointly affect some 30 million citizens in Europe alone. Today, there is as EU-funded research developed enzyme-replacement therapy to stop the illness in its tracks, and this medicine is on the market.
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Alpha-mannosidosis is an inherited condition linked to a gene that codes for one of the enzymes our bodies must produce. The EU-funded ALPHA-MAN project conducted trials that involved dosing patients with a replacement enzyme in a bid to halt the progression of the disease.
This was the last of three successive EU-funded projects that paved the way for the commercialisation of the first-ever drug specifically targeting alpha-mannosidosis, according to Paul Saftig of Kiel University, Germany, who led the research. The new drug, named Lamzede, significantly improves patients quality of life, Saftig notes. It was approved by the European Medicines Agency in 2018.
In 2019, the Horizon Impact Awards added to the resonance of this success story. Lamzede was one of the innovations for which the European Commission awarded this prize as part of the inaugural edition of this contest, which celebrates EU-funded projects that have been particularly effective in generating benefits for society.
Support for struggling cells
Alpha-mannosidosis is a very rare disease according to estimates, it affects about 300 patients in Europe. The new treatment can reverse some although not all of the symptoms that may have begun to unfold, and can prevent or at least delay further damage, Saftig explains.
It is designed to compensate for the fact that, in alpha-mannosidosis, an enzyme that breaks down specific types of sugars in our cells is either flawed or not produced at all, leading to a build-up of residues. At some point, the cell just gives up, and this causes major problems, says Saftig.
More specifically, over time, this accumulation causes abnormalities in different types of tissue the disease can affect patients bones or muscles, for example, or their central nervous system, he explains. This phenomenon explains the wide variety of symptoms patients may present with.
From insight to innovation
The string of projects that delivered Lamzede began in 2001, with fundamental research into the pathways of the disease. Nine years on, the work had advanced to the point where an actual drug was available for testing. ALPHA-MAN was launched in 2010 to conduct the first human trials of treatment with an enzyme that its predecessor projects had found a way to produce in sufficient quantities.
The researchers had also managed to replicate the same genetic specificity in mice, on which the treatment had already been tested successfully, and to identify physiological markers of this illness able to assess its effectiveness, Saftig explains. In addition, they had compiled a database describing the genetic and physiological aspects of the illness in many of Europes few known patients. And, just as importantly, a productive collaboration had been established among scientists, clinicians and other experts across Europe, all contributing their particular know-how.
Enzyme replacement therapy was not new, but it had not yet been harnessed for this particular illness. Without the EUs support, I doubt this drug would be available. The individual partners alone would not have had the power or means to muster all the forces needed to establish the knowledge, tools and the patient contacts, etc., Saftig says.
More generally, continued backing from the EU also helps to build a convincing case for potential investors: It implies quality control and indicates that the prospective product is very valuable.
For Saftig personally, EU endorsement across three successive projects has also meant that he was able to take the idea through the entire process, transforming a promising idea into a pharmaceutical product.
Its a rare privilege for a scientist to develop something from the fundamental research to the moment an actual treatment is approved, Saftig concludes.