A spotlight on neuro-degenerative diseases

Senile dementia or Alzheimer's disease? Tremors or Parkinson's disease? In fifty years, physicians have learned how to discern these symptoms, and the knowledge of normal and pathological ageing has not stopped growing. However, advances in treatment have been slow to emerge. Yves Agid, a founding member of the Brain and Spinal Cord Institute in Paris, reflects on the advances made in the last half-century.

These last fifty years have been marked by the emergence of neuro-degenerative diseases. Not because they appeared suddenly during the 20th century; but because clinicians were slow to distinguish normal physiological ageing from pathological ageing. “People blamed everything on senility 50 years ago: Doctor, he’s losing his mind. It’s his age, we said. Today, an individual takes his/her spouse for a consultation and asks: Doctor, is it Alzheimer’s disease?” observes Yves Agid, who has devoted his life to studying these diseases. This attitude is a good indication of the considerable progress made in the area of neuro-degenerative diseases.

A close-up look at neuro-degenerative diseases
These diseases are characterised by the progressive destruction of a targeted and defined population of nerve cells. This neuronal death is more rapid than that observed during normal ageing, and occurs in a defined region of the central nervous system. This may be areas of the cortex associated with intellectual and emotional functions (Alzheimer’s disease), structures deep in the brain that are more involved with motor function (Parkinson’s disease, Huntington’s chorea), the cerebellum, with problems of coordination and balance (ataxia), the spinal cord (amyotrophic lateral sclerosis) or the peripheral nerves (Charcot-Marie-Tooth disease). These disease families are already common, and risk becoming more so given the increase in life expectancy.

Director of Inserm Research Unit 289, devoted to the study of diseases of the nervous system, Yves Agid was subsequently Head of the Neurology Service and Scientific Director of the Brain and Spinal Cord Institute until 2011. This practitioner and researcher is therefore well placed to recognise the scientific and medical advances made in this area. “The identification of the cells destroyed in these different diseases, and the study of the mechanisms contributing to the dysfunction and death of these cells have been very useful in learning how to diagnose these disorders early and design treatments. These remarkable advances have been made possible by a better characterisation of clinical symptoms, by the identification of genetic and environmental factors underlying these diseases, and also by the spectacular advances in neuroimaging and neurophysiology*. Fifty years ago, we did not always make the distinction between benign forgetfulness and Alzheimer’s disease, whereas in one case it is a matter of ageing and in the other a disease. Today we have the clinical and biological elements that enable diagnosis of most neuro-degenerative diseases with great certainty.”

Understanding the mechanisms

© Inserm, U837

Researchers are also starting to understand the dysfunction of the main metabolic pathways underlying these diseases. They have, for example, discovered that the presence of senile plaques and neurofibrillary degeneration play an essential role in the loss of nerve cells that gives rise to Alzheimer’s disease, and that the disappearance of dopaminergic neurons and presence of Lewy bodies contribute to Parkinson’s disease. However, there is still a long road to travel before all these mechanisms are deciphered. “The human brain is so very complex! We are talking about a hundred billion neurons making several thousand contacts with their neighbouring cells. Fifty years ago, scientists agreed that neurons could not replicate. Today, we know that some of them have this ability. We imagined that a loss of nerve cells was permanent and without hope. Today, we observe that the reconfiguration of circuits allows compensation for the loss of these neurons, providing a certain level of clinical recovery. We must evaluate all these aspects in neuro-degenerative diseases. That is to state the size of the task to come,” he observes.

Improving treatments

Despite this progress, advances in treatment are slow to appear. “We are certainly making progress on the treatment front, but slowly!” admits Yves Agid. We can improve the symptoms up to a certain point, but not prevent their appearance or their progression. In other words, we can provide partial relief for patients, but we do not know how to cure them. For Huntington’s chorea, which is a genetically inherited disease, we know the gene involved, we can diagnose the disease before birth, but we cannot prevent its ultimate occurrence...,” the researcher regrets. However, some diseases, especially Parkinson's disease, have been greatly alleviated by effective treatments—medical, by substitution treatment with L-dopa, or neurosurgical, by targeted electrical stimulation with the help of electrodes implanted in the brain.

*exploring the anatomical and physiological organisation of the cells of the central nervous system

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