Potential neuroprotective effect in neurodegenerative diseases

and a favorable safety profile

Pridopidine is an orally bioavailable small molecule investigational drug exhibiting potential neuroprotective effect in multiple neurodegenerative diseases with a favorable safety profile.


Pridopidine is the most selective high affinity Sigma-1-receptor (S1R) agonist. The S1R regulates key cellular processes relevant to neurodegenerative diseases, such as calcium homeostasis, cytoskeleton dynamics, restoring mitochondrial health and neurotrophic factor release. S1R is implicated in cellular differentiation, neuroplasticity, neuroprotection, and cognitive functioning of the brain.


Pridopidine positively influences S1R regulated pathways across neurodegenerative and neurodevelopmental indications, including protection against axonal and neuronal injury, restoring spine impairments, enhancing BDNF secretion and restoring mitochondrial function. These mechanisms have been validated in multiple disease models including Huntington Disease (HD), ALS, Neurodegenerative eye disease, Parkinson’s Diseases (PD), Rett Syndrome (RTT), Fragile X and Alzheimer Disease (AD).  Pridopidine’s occupancy of the S1R (full occupancy at low doses) has been validated using PET imaging in humans.


Pridopidine’s favorable safety profile has been established in clinical trials in >1300 subjects, exposed to various doses for a total of ~1300 patient years. This extensive safety evaluation supports a favorable safety and tolerability profile which has been well defined.



HD is a fatal, inherited, neurodegenerative disorder where every offspring of an HD patient has a 50% chance of inheriting the gene. Usually starting at around 40 years of age, HD patients suffer from a progressive movement disorder, functional and cognitive decline, psychiatric disturbances and behavioral symptoms. Following diagnosis, functional, motor and cognitive functions decline steadily, ultimately leading to immobility, dementia and premature death.

The prevalence of HD  in North America, North-Western Europe and Australia ranges from 5.96-13.7 cases per 100,000 people. In the US and Europe   there are approximately 80,000 people who have HD. For every affected person, there may be 2-4 offspring who inherit the mutation. in whom the disease will appear if they live long enough. Currently there is no approved treatment for functional decline in HD. Only two drugs are approved for relieving certain motor symptoms such as chorea. Pridopidine has shown to maintain functional capacity in HD, as measured by Total Functional Capacity (TFC), in a clinical trial. This effect was most prominent in early stage HD patients (HD1 and HD2), for which pridopidine 45 mg bid showed significant functional benefit.

Pridopidine Outcome On Function in Huntington’s Disease (PROOF-HD) is an active global phase 3 trial, currently enrolling patients with early stage of HD. The purpose of the study is to evaluate the effect of pridopidine 45mg bid on functional capacity, as well as on motor and behavioral features. The study is designed to replicate previous findings that demonstrated pridopidine’s effect in maintaining functional capacity in patients with early HD.

There is extensive preclinical evidence that further supports pridopidine’s potential beneficial effect in HD. This effect is mediated exquisitely by the S1R, as shown in multiple models. When S1R is deleted or antagonized no beneficial effect can be seen .

Prilenia has an orphan drug designation for pridopidine for the treatment of HD in both the US and Europe.



Amyotrophic lateral sclerosis, ALS, is the most prevalent adult-onset progressive motor neuron disease, affecting approximately 30,000 people in the U.S. and an estimated 500,000 people worldwide. ALS causes the progressive degeneration of motor neurons, resulting in progressive muscle weakness and atrophy.

Compelling preclinical data supports the potential use of pridopidine as a therapeutic for ALS. In ALS SOD1G93A motor neurons (MNs), pridopidine exerts neuroprotective effects via activation of the S1R. Specifically, pridopidine improves BDNF (brain-derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) axonal transport, restores synaptic activity and neuro-muscular junction (NMJ) function, and increases neuronal survival. In vivo, pridopidine treatment of SOD1G93A mice reduces toxic protein aggregates and ameliorates muscle fiber wasting. The sigma 1 receptor has been genetically validated for ALS, as patients with mutations in this gene develop ALS.


Previous clinical data also suggest that S1R is a promising target for ALS therapy, indicating that S1R activation may enhance bulbar and speech function in ALS patients.

Pridopidine in-vivo target engagement in humans is validated by PET imaging, providing support for the optimal clinical dose.

Pridopidine has recently been selected by the Sean M. Healey & AMG Center for ALS at Mass General Hospital, as the first of five potential new treatments to be included in the launch of the first ever Platform Trial in ALS.

Pridopidine was chosen by an independent review committee out of 30 competing investigational treatments based on human genetic data, efficacy in preclinical models, favorable safety profile, readiness of drug supply, as well as pridopidine’s mechanism of action as a highly selective S1R agonist.

The Platform Trial design aims to accelerate the development of effective treatments for people living with ALS, by testing and evaluating multiple treatments simultaneously. The trial is currently active and recruiting.



In addition to the HD and ALS programs, Pridopidine is also being studied in various neurodegenerative and neurodevelopmental indications including Parkinson’s Disease Levodopa Induced Dyskinesia

(PD-LID), Rett Syndrome and Fragile X syndrome.