Lithium shows promise in mouse model of devastating neurodegenerative disorder
Lithium is one of the oldest psychiatric drugs and still used routinely to ameliorate the symptoms of mood disorders. New results by Huda Zoghbi (Baylor College of Medicine and Howard Hughes Medical Institute), Harry Orr (University of Minnesota) and colleagues now suggest that lithium also holds promise in treating a group of devastating neurodegenerative disorders for which no other treatments exist at present. As the researchers report in the international open-access medical journal PLoS Medicine, dietary lithium markedly improved the symptoms in a mouse model of spinocerebellar ataxia.
Spinocerebellar ataxia type 1 (SCA1) is part of a group of inherited, incurable neurodegenerative disease called triplet repeat diseases. These diseases kill patients (who are typically diagnosed in their thirties and forties) within a few years of disease onset. The name refers to the underlying genetic abnormality: Information for making proteins is stored in DNA as groups of three nucleotides (codons), each specifying a different amino acid (the building blocks of proteins). In triplet repeat diseases, patients inherit a mutant gene containing abnormally long stretches of repeated codons. In SCA1, the repeated codon is CAG, which specifies glutamine, and patients have an abnormal glutamine stretch in the Ataxin1 protein. This stretch causes Ataxin1 to accumulate and to have altered protein interactions that are toxic to a group of cerebellar neurons called Purkinje cells (which normally coordinate movement) and hippoca mpal neurons (which are important for memory). Patients gradually lose movement control, have impaired cognitive function, and eventually die from the disease because other neurons in the brain stem also degenerate.