ALS: from genetic defects to novel therapies
ALS: from genetic defects to novel therapies
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease affecting some 50,000 individuals at any time in Europe, and causing around 10,000 deaths each year. ALS is characterized by progressive degeneration of motor neurons in brain and spinal cord leading to muscle weakness. ALS can occur in any individual at anytime during adulthood. Initial manifestations are weakness of limbs or weakness in the bulbar region leading to abnormalities of speech, swallowing difficulties and facial weakness. The patient becomes paralyzed and dies as the result of respiratory failure. There is no cure for ALS. The only available drug (Riluzole) is marginally effective in extending the life span of ALS patients with 3-6 months.
Novel treatment options are needed for this disabling and fatal disease. The lack of treatment in ALS can be attributed to an absence of validated therapeutic targets reflecting an inadequate understanding of disease mechanisms. Elucidating the ALS pathogenic mechanism is therefore essential to pave the road for therapeutic interventions. Several projects in the lab are focused on unravelling the molecular mechanisms defective in in familial and sporadic ALS.
An important starting point of our work are genetic defects detected in ALS patients (e.g. detected in ProjectMinE). Using different molecular cell biological, -omics, and biochemical approaches in different model systems (e.g. IPSC-generated neurons or organoids) we aim to understand how specific genetic defects cause ALS and on basis of this knowledge design therapeutic strategies. This work is in part supported by the Prinses Beatrix Spierfonds and Stichting ALS Nederland. In addition to ALS we also study other motor neuron disorders such as spinal muscular atrophy (SMA) and multifocal motor neuropathy (MMN).
