What is pridopidine?

  • A small molecule investigational drug in clinical trials for ALS and Huntington disease (HD) (neurodegenerative diseases)
  • Pridopidine is a dministered orally twice a day (BID), in the morning and in the afternoon
  • Pridopidine binds and specifically activates a receptor called the Sigma-1 receptor
  • Pridopidine is safe and tolerable. The dose tested for ALS has a side effect profile like that of placebo in clinical studies in Huntington disease.
  • In patients with Huntington disease, pridopidine is the first drug to show maintenance of total functional capacity (TFC).
  • This effect is durable up to 5 years (longest time that has been analyzed to date)
  • TFC is the most accepted scale used to assess a HD patient’s function and disease progression, and is accepted by the regulatory agencies as a single primary endpoint in clinical trials

What is the Sigma-1 Receptor (S1R)?

  • A protein highly expressed in the brain and spinal cord, particularly in motor neurons
  • Plays an important role in the cell's response to stress
  • Activation of the S1R has neuroprotective effects:
  • Reduces neuronal degeneration and death
  • Enhances neuronal health and function by increasing energy production and clearanc of toxic proteins
  • Increases neuronal connectivity
  • Reduces cellular stress and neuroinflammation

Why is the S1R a good target for ALS?

Why test pridopidine for ALS?

  • In ALS mice, the connection between neuron and muscle is disrupted (left)
  • Pridopidine rescues this connection (neuron + muscle labeling shows as yellow on the right)