Tau protein with an excessive number of phosphate groups attached, causing it to detach from microtubules, misfold, and aggregate into toxic NFTs that disrupt neuronal function.

Significant impairment in the ability to perform normal motor actions.

A reduction in glucose uptake and energy activity in specific brain regions, seen as areas of low tracer signal on FDG-PET, usually reflecting neuronal dysfunction or loss.

A diagnosis reinforced by findings from imaging techniques (e.g., MRI, PET) that show disease-specific changes.

A type of therapy based on stimulating or suppressing the immune system.

The number of new cases of a disease occurring in a specific population over a specific period of time.

Located or occurring within the interior of a cell.

Variants of a protein that can slightly differ in structure and function. E.g. tau can appear as 3R and 4R.

Involuntary, large-amplitude, horizontal eye movements that temporarily move the eyes away from and then back to a fixation point.

The specific physiological process through which a drug produces its therapeutic effect in the body.

Refers to cognitive and mental functioning, such as thinking, memory, attention and judgement.

Cylindrical protein filaments forming part of the cell’s cytoskeleton, essential for maintaining cell shape, intracellular transport, and cell division.

An incorrect identification of a disease, often leading to inappropriate treatment or delays in receiving appropriate treatment.

Laboratory-produced antibodies engineered to recognize and bind specific antigens.

In medicine, the term is used as the number of deaths in a population during a specific period of time.

Group of neurological conditions primarily affecting the control of voluntary and involuntary movements, resulting in symptoms such as stiffness, slowness or tremors.

An integrated approach to care provided by a team of specialists. In the case of PSP, the multidisciplinary team may include, but are not limited to: neurologist, nurses, physiotherapist, speech therapist, psychologist, dietician, social worker, etc.

Brief, involuntary muscle contractions.

Condition characterized by progressive loss or damage of neurons.

Clumps of abnormal tau inside neurons that disrupt their function and lead to cell death.

Structural proteins of neurons; their breakdown products in blood or CSF reflect non-specific axonal damage and neurodegeneration.

Chronic inflammatory response of the central nervous system to damage, often contributing to neurodegeneration and disease progression.

A reversible post-translational modification in which an N-acetylglucosamine (GlcNAc) molecule is added to a protein, regulating its folding, phosphorylation, and degradation. Increased O-GlcNAcylation of tau may counterbalance hyperphosphorylation and promote neuronal survival.

Abnormalities in controlling eye movements, affecting gaze stability and visual tracking.

A molecule that inhibits O-GlcNAcase, increasing protein O-GlcNAcylation and reducing phosporilation, proposed to restore tau homeostasis and reduce neurodegeneration in PSP (i.e. Egalognastat / FNP-223).

Abnormal tau-positive inclusions found within the cytoplasm of oligodendrocytes.

p-tau217 is a phosphorylated form of the tau protein at threonine residue 217, and it serves as a highly specific and sensitive biomarker for Alzheimer's disease (AD) pathology. Measurement of p-tau 217 in plasma or cerebrospinal fluid (CSF) reflects abnormal tau phosphorylation associated with neurofibrillary tangle formation. Compared to other phosphorylated tau isoforms (such as p-tau181), p-tau 217 demonstrates superior diagnostic accuracy for distinguishing AD from non-AD neurodegenerative disorders, including progressive supranuclear palsy (PSP).

Clinical syndrome characterized by bradykinesia plus rigidity, tremor, or postural instability.

The sequence of patients’ experiences and perspectives through stages of care - from symptom onset to diagnosis, treatment, and ongoing disease management.

An imaging technique using positron emission tomography (PET) to visualize and measure metabolic or molecular activity in tissues, often applied in neurology to assess brain function or pathology. 

The biological and physiological effects of drugs on the body, including the mechanism of action at the target site. (It answers the question: "What does the drug do to the body?").

The characterization of how a drug is absorbed, distributed, metabolized, and eliminated by the body over time. (It answers the question: "What does the body do to the drug?).

The first stage of clinical research in humans, primarily assessing a drug’s safety in a small group of healthy volunteers or patients.

The second stage of a clinical trial aimed to evaluate a drug’s efficacy and short-term safety in patients.

The last stage of a clinical trial before licensing. A large-scale clinical trial designed to confirm a drug’s efficacy and safety to support regulatory approval.

The set of observable characteristics (symptoms, clinical signs) that define different forms of a disease. In PSP, several variants have been described: PSP-RS, PSP-P, PSP-PGF, PSP-CBS, PSP-SL, PSP-PI, PSP-OM, PSP-F, PSP-C, PSP-PLS.

A post-translational modification in which a phosphate group is added to a protein or other molecule, regulating its activity, function, or signaling properties.

Extreme sensitivity to light.

An inactive substance designed to resemble the experimental treatment, used as a control to measure the true effect of the active drug.

Trial design in which the effects of an active treatment are compared with those of an inactive substance (placebo) to assess the true efficacy of the intervention.

Chemical or structural changes made to proteins after their synthesis, altering their function, stability, or interactions.

Loss or dysfunction of dopamine-receiving neurons in the striatum, leading to impaired motor signaling.

Research conducted before testing in humans, using laboratory and animal studies to evaluate the pharmacological, toxicological, and pharmacokinetic properties of a drug.

Stage where the disease is already present in the brain, but no symptoms are visible yet.

The total number of cases of a disease in a population at a specific point in time or over a defined period.

Process in which abnormal proteins (e.g., NFTs) spread from cell to cell, converting healthy proteins into the same harmful form and spreading the disease throughout the brain.

The predicted outcome of a disease, including likelihood of recovery or recurrence.

A disease that worsens over time in terms of extent or severity.

PROSPER is an ongoing multinational, randomised, double-blind, placebo-controlled Phase 2 study to assess the safety, tolerability and efficacy of FNP-223 administered orally at a dose of 300 mg three times a day in adults aged 50–80 years with early-stage possible or probable PSP-RS.

Process in which misfolded proteins clump together, forming toxic deposits in the brain, like tau in tauopathies.