The Generet Award for Rare Diseases, now in its fifth year, has been awarded to Prof. Dr Ludo Van Den Bosch for his research into the underlying mechanisms of amyotrophic lateral sclerosis (ALS), a rare form of motor neuron disease. This award from the Generet Fund, managed by the King Baudouin Foundation, is accompanied by a grant of €1 million, making it the most prestigious prize in Belgium for work on rare diseases. The jury of independent experts praised Prof. Dr Van Den Bosch's ambition to improve patients’ lives with ALS through his research.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the nerve cells that make movement possible. The condition, also known as Lou Gehrig’s Disease, selectively affects motor neurons, the cells that communicate with the muscles. As a result, people with ALS gradually lose control of their muscles until they are completely paralysed and unable to speak and breathe. The disease is incurable, with the age of onset typically relatively young (between 50 and 60). Patients usually die within two to five years of diagnosis. In Belgium today, about 1,000 people are suffering from this disease and 100 to 250 new diagnoses are made every year.
Ludo Van Den Bosch has been studying the underlying mechanisms of this neurodegenerative disease for many years at the Laboratory for Neurobiology at KU Leuven/VIB, Belgium's leading centre for the study of ALS. The research is carried out in close collaboration with Prof. Philip Van Damme, a neurologist at Gasthuisberg University Hospital in Leuven, and with the ALS League, a Belgian association of ALS patients. They work intensively with national and international research groups and are part of the European Network to Cure ALS (ENCALS), Project MinE, and the Robert Packard Center for ALS Research in the United States.
Cause usually unknown
“In 90% of patients, the cause of the disease is unknown, while in the remaining 10% it is genetically determined - in other words, there will be multiple family members who suffer or have suffered from the disease,” explains Ludo Van Den Bosch. “We've developed various models for ALS in the lab. For example, we use fruit flies, zebrafish, and rodents to study the disease process better. For several years now, it has also been possible to make induced pluripotent stem cells (iPSCs) from patient skin cells. These cells can be converted into motor neurons and muscles having the same characteristics as those in ALS patients. This enables us to study the disease with greater precision.”
Altered neuronal transport
Ludo Van Den Bosch and his team of researchers have discovered that, in ALS patients, transport along the processes that connect the cell body in the spinal cord to the muscles is disrupted. These processes can be more than a metre long, and normal transport in these processes is critical for the normal functioning of the motor system: “We discovered that we can restore disrupted transport by selectively inhibiting a certain enzyme, HDAC6”, Van Den Bosch says. “In addition, inhibiting HDAC6 also has beneficial effects on the expansion of motor neuron processes and the formation of neuromuscular junctions, the connections between the motor neuron processes and the muscles.”
Ludo Van Den Bosch and his team will use the financial support associated with the Generet Prize to continue researching the positive effects of HDAC6 inhibition on motor neurons. In doing so, they will examine which mechanisms are responsible for these beneficial effects and will determine which proteins HDAC6 influences and how the inhibition of this enzyme induces this effect.
The therapeutic ambition is clear: “The ultimate goal of this scientific research is to translate these new insights into the action of HDAC6 inhibition into a new therapeutic strategy that can be tested in ALS patients,” says Ludo Van Den Bosch. “We hope to make an important contribution towards finding a cure for this rare and fatal neurodegenerative disease.”
Laboratory of Prof. Van Den Bosch
Press release of the King Baudouin Foundation