October 9, 2013

expert reaction to compound that arrests neurodegeneration in mice

Science Translational Medicine published a UK study showing success for a potential new drug treatment for prion disease in mice, suggesting it could also hold benefits for the treatment of other neurodegenerative diseases like Alzheimer’s. 

Prof Roger Morris, Acting Head, Department of Chemistry, King’s College London, said:

“This is the first convincing report that a small drug, of the type most conveniently turned into medicines, stops the progressive death of neurons in the brain as found, for instance, in Alzheimer’s Disease. True, this study has been done in mice, not man; and it is prion disease, not Alzheimer’s, that has been cured.  However, there is considerable evidence that the way neurons die in both diseases is similar; and lessons learned in mice from prion disease have proved accurate guides to attenuate the progress of Alzheimer’s disease in patients. From finding the first effective drug in a mouse, to having an effective medicine in man, usually takes decades to bring to fruition, in the very few cases in which it is successful. So, a cure for Alzheimer’s is not just around the corner.  However, the critical point of principle made by Professor Mallucci’s study is that a drug, given orally, can arrest neurodegeneration caused by amyloid in the brain.   The manner of its discovery should also be noted – very careful, basic research in mice with carefully controlled prion disease revealing a mechanism common to the neuronal response to amyloid in mice and men.

“This finding, I suspect, will be judged by history as a turning point in the search for medicines to control and prevent Alzheimer’s Disease.” 

Prof David Allsop, Professor of Neuroscience, Lancaster University said:

“A number of brain diseases including prion disease (e.g. CJD in humans), Alzheimer’s disease and Parkinson’s disease are caused by the build-up of ‘misfolded’ proteins in the brain, which change their normal shape and then ‘stick together’ to form fibres, which can accumulate both inside and outside of nerve cells. Instead of trying to prevent the build-up of these protein fibres, these researchers have targeted a specific biochemical pathway that is activated in response to the change in protein shape. Inhibiting this pathway has produced some very dramatic and highly encouraging results in mice infected with prion disease. The main caveats of the research, however, are that prion disease is very rare in humans, and it is not yet clear if the same approach will be viable for much more common neurodegenerative conditions like Alzheimer’s disease and Parkinson’s disease.  Also, the treatment produced some serious side effects, including significant weight loss and elevation in blood glucose levels, which would be problematic for elderly people with Alzheimer’s disease for example, who can already suffer from weight loss problems. More research is needed to determine if this approach is valid for any condition other than prion disease, and also to find ways of getting around these problematic side-effects.”

Dr Michel Goedert, Joint Head, Division of Neurobiology, MRC Laboratory of Molecular Biology, said:

“Pharmacological inhibition of the protein kinase PERK protected significantly against prion-mediated neurotoxicity in a mouse model of disease. Abnormal aggregation of known proteins also underlies Alzheimer’s disease, Parkinson’s disease and a number of other neurodegenerative diseases. It will be exciting to see if PERK inhibition is neuroprotective in animal models of these diseases.”

‘Oral treatment targeting the unfolded protein response prevents prion neurodegeneration and clinical disease in mice’ by Julie Moreno et al., published in Science Translational Medicine on Wednesday 9 October 2013.