Rebooting Parkinson’s research with mini-brains

Parkinson's Disease is a neurological disorder primarily caused by degeneration of specific neurons that results in tremors, rigidity and loss of voluntary movement. Like many other devastating neurological diseases, treatment is limited and there is no cure. Millions of dollars have been invested over decades to study animal models with no real success.

Now a company in Luxembourg, Organo-Therapeutics, is directing its focus on utilizing human stem cell technologies to create “mini-brains” to develop treatments for Parkinson’s Disease.  Founders Javier Jarazo, PhD and Jens Schwamborn PhD, a professor at the University of Luxembourg, hope to demonstrate that disease research can be done without the use of animals.


forced swim

To understand how much more promising this approach is over animal experiments, it’s necessary to know how animal models are created. Because scientists do not have a full understanding of what goes wrong in Parkinson’s Disease, animal research is based on chasing down a number of theories involving gene mutations, infections, and inflammation. In other words, they are largely groping in the dark.

Using neurotoxins that cause brain inflammation, or gene insertions that are suspected to play a role in Parkinson’s, researchers turn animals into so-called models of Parkinson’s Disease.

By contrast Organo-Therapeutics looks directly at examining the pathophysiology of human Parkinson’s cells. They create “mini-brains” by taking donated stem cells from patients suffering from Parkinson’s Disease and differentiate them into 3D structures resembling the midbrain, the part of the brain that is primarily affected by Parkinson’s Disease.  These mini-brains will be treated with two drugs believed to prevent the nerve cell death that is typical in Parkinson’s. Next, the mini-brains will be analyzed with high-end microscopy and computational methods to confirm the results.

This precise, clear-cut and human-relevant model is a world apart from chaotic, ill-defined and brutish animal experiments.

Typically, monkey models are created through the use of neurotoxins, as in an experiment in which the compound MTPT was injected directly into the brain to cause a Parkinsonian-like syndrome. Monkeys had electrodes implanted for additional brain mapping studies, while placed into restraint chairs during experiments.

These monkeys spend their lives in confinement, afflicted with brain damage, and tethered by wires protruding from their skulls. There is no way to measure how much their misery affects the scientific outcomes.

In another disturbing experiment, scientists wanted to see whether a specific gene influenced by infection would show a connection to Parkinson’s Disease. They caused severe sepsis in mice by intravenous infusion of Salmonella, while inducing encephalitis, a painful brain infection, in newborn mice by injecting the virus into their noses. This ruthless and unfocused research was simply to explore a theory, that if correct, would impact only 2% of Parkinson’s patients with that particular gene defect.

Parkinson’s patients are not ill because they received a dose of neurotoxin. Their disease arises from some intricate and microscopic dysfunction that occurs within the cell or cell interactions.  It’s clear that a method that can grow and examine cells from Parkinson’s patients is far superior to damaging animals’ brains to glean information that may have relevance for Parkinson’s Disease.

In fact, earlier this year, Organo-Therapeutics released a publication demonstrating for the first time that their mini-brain model exhibits “disease relevant alterations” characteristic of Parkinson’s Disease.

As Dr. Schwamborn explained in an email to CAARE: “In the past endeavors to develop new therapeutic strategies, which are not only symptomatic, largely failed. We are convinced that using human patient specific models, like our mini-brains will dramatically reduce the failure rate, and therefore help to bring better medications into clinical testing and eventually to the patients.”

Organo-Therapeutics is raising funds to begin this exciting work with their crowdfunding campaign: Medication development free of animal testing.

CAARE is pleased to have donated to support the campaign and we encourage others to do so as well. We believe human-relevant technologies like Organo-Therapeutics’ mini-brains will serve as a model for other scientists to follow, bringing much-needed treatments to patients, and helping to eliminate the extreme, needless suffering of animals.

Citizens for Alternatives to Animal Research (CAARE), is a 501(c)(3) non-profit organization, established to highlight and promote research without animals.

Please donate to support CAARE’s mission to end animal suffering by disseminating information about the power and progress of research without animals.