Lorenz Studer on Day 1 #ISSCR2018: HESC-based therapies for Parkinson’s Disease

GForce_Superhero_logo Parkinson's Disease
monkey-graft; hPSC-derived dopamine neurons in Parkinsonian monkey brain; Studer Lab

One of the highlights of Day 1 of #ISSCR2018 for me so far was the talk by Lorenz Studer (Co-Founder of BlueRock) on the use of human embryonic stem cell (HESC)-derived dopamine neurons for Parkinson’s Disease.

Note that for this post and if I have time any others on this meeting, they are probably going to be somewhat stream of consciousness notes from the talks and may have some outlined points rather than sentences.

I have some questions or notes for myself that I put in parentheses and/or underlined.

Background on Parkinson’s Disease from his talk:

  • 1 million US, 5 million worldwide have the disease
  • 1/100 people over 60 will have Parkinson’s Disease
  • Early fetal transplants (e.g. NEJM 1995 27;332) had some success, but some side effects (I’m remembering dyskinesia from that work).

The team is hoping that post-transplant that cell-cell interactions may be beneficial both via dopamine and other mechanisms like synaptic connectivity.

They recently went into manufacturing mode. They are close to an IND, which is fantastic news.

Then gave some interesting technical details on the work.

  • Temporal gene expression analysis repeatedly on cells for QC
  • Made 10 billion cells; 1,000 doses (do you need >1 dose per Parkinson’s Disease patient?)
  • Cells stable at 4deg & in LN2
  • OCT4 gone; FOXA2 up as cells differentiate

It’s encouraging to hear where they are at on the regulatory path.

  • Pre-pre-IND; generally OK 8/2014
  • Pre-IND meeting; no major concerns 5/2016
  • GLP:  Then did more mouse studies >400 mice, 6-10 months (completed!)
  • NON-GLP: efficacy done in rat, 48 animals ; short-time non-human primate study (done)
GForce_Superhero_logo Parkinson's Disease
G-Force PD logo; GForce_Superhero_logo Parkinson’s Disease

They are aiming with the MSK-DA01 clinical trial to be a Phase I/IIa combined study. Here are some details on the design.

  • Patients Age 40-70; try low and high dose
  • Bilateral injections (people normally have 400,000 dopamine neurons on each side of the brain); 3 tracks for depositing cells
  • Immunosuppression 1 day prior, up to 12 months following transplantation
  • Weill Cornell; MSK

He also mentioned the G-Force PD, Parkinson’s Disease global team. Gotta love their logo.

Finally, briefly discussed a different project — NFIA induces glial competency; can make astrocytes that seem somewhat functional, they engraft, migrate.

This is an exciting time for PD research.

2 Comments


  1. Excellent summary Paul. And congratulations to Lorenz Studer. My own bit of homework into DA cells revealed remarkable facts – emphasising further the significance of the report….I extract from review DOI: 10.2174/1381612822666161206 141744
    “Human dopaminergic neurons are especially vulnerable to stress due to the high energy demand required to meet their massive unmyelinated axonal arbor that involves more than one million synapses per cell: the calculated total axonal length of a single DA neuron exceeds 4m. [21] Thus, for the transplanted DA cell, the level of cell inte-gration required to replace lost endogenous dopaminergic activity is profound: the situation is further compounded by the DA cell’s inherent vulnerability to stress once integrated into the host where the grafted DA neurons need to migrate within the host tissue and their axons must extend to reach their targets.”

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