Progressive supranuclear palsy (PSP): causes, biological mechanisms, symptoms, diagnosis, treatments

Progressive supranuclear palsy (PSP), also known as Steele-Richardson-Olszewski syndrome, is a rare neurodegenerative disease affecting between 5,000 and 10,000 people in France, with onset between the ages of 40 and 60. It accounts for 3 to 6% of atypical Parkinsonian syndromes. The clinical picture is similar to that of Parkinson's disease, but with specific clinical signs, such as instability of posture leading to backward falls (retropulsions), backward hypertonia of the neck muscles (retrocollis), and eye movement disorders or paralysis.

The causes and biological mechanisms of progressive supranuclear palsy

Progressive supranuclear palsy is characterised by the abnormal accumulation of a protein, the tau protein, in neurons, leading to their degeneration. PSP is described as a TAUpathy. The exact cause of progressive supranuclear palsy is still unknown. The hypothesis of a multifactorial disease has been put forward: a genetic predisposition coupled with an environmental influence is probably at the origin of the pathology, but the disease is not hereditary. In only a few dozen families worldwide has a mutation in a gene coding for a microtubule protein been identified.

Neuronal death linked to the accumulation of the TAU protein affects all regions of the brain, but most significantly the basal ganglia and the brain stem. The basal ganglia are brain structures that initiate and harmonise voluntary movements and control changes in posture. The brain stem regulates vital functions such as breathing, heart rate and swallowing.

Symptoms and diagnosis of progressive supranuclear palsy

Progressive supranuclear palsy combines motor symptoms such as instability of posture, muscular rigidity that may even lead to occlusion of the eyelids, eye movement disorders and cognitive and behavioural symptoms such as mood instability, with the patient exhibiting involuntary crying or laughter. The diagnosis of progressive supranuclear palsy is based on neuropsychological tests, brain imaging using MRI and/or PET scans, and an oculomotor examination to identify any eye movement disorders.

Treatment for progressive supranuclear palsy

At present, there are no drug treatments that can cure PSP. However, certain treatments generally prescribed for Parkinson’s disease can reduce some of the symptoms experienced by PSP patients at the onset of the disease.

Treatment for progressive supranuclear palsy is symptomatic and multidisciplinary, involving physiotherapy and speech therapy to combat progressive muscle rigidity and keep joints supple for as long as possible, thereby limiting the risk of falls.

In 2019, the French National Agency for the Safety of Medicines (ANSM) has authorised the launch of a phase 2a clinical trial with the drug candidate AZP2006 . This therapeutic trial is being conducted at La Pitié Salpêtrière Hospital in Paris (AP-HP), under the direction of Professor Jean-Christophe CORVOL, neurologist and researcher at the Institut du Cerveau and at Lille University Hospital, in Professor DEFEBVRE’s department.

Last updated in May 2024.