“When a clinical trial fails at a late stage, it’s devastating for everyone involved - the patients, their families, doctors and researchers. And for Parkinson’s disease, this has happened too many times,” says Sonia Gandhi, who leads the Crick’s Neurodegeneration Biology Laboratory and also treats patients at the National Hospital for Neurology and Neurosurgery.
“The biggest problem with many neurodegenerative diseases is the long and slow accumulation of physical and cognitive disability. If we could find a way to delay the onset of symptoms, or slow progression, by even just a few years it would make a huge difference to patients. But researchers have spent about three decades developing so-called ‘disease modifying’ treatments and none have made it through clinical trials.”
Sonia’s research team is looking to change this pattern of disappointment by developing new treatments that are based on better biological models of Parkinson’s disease. They hope that improving our understanding of the genetic changes that drive neurodegeneration will help uncover new targets for treatments, and importantly, that these will be more likely to be effective in patients.
Their study is one of many collaborative projects between Crick and Industry scientists, developed through the innovative early discovery research frameworks established with MSD, GSK and AstraZeneca.
Paul Mercer, Head of Collaboration at the Crick helps bring teams together, developing projects ranging from fundamental understanding disease mechanism, technology development for drug discovery, through to biomarker discovery to enhance design of therapeutic interventions and improve patient outcomes. He says: “We aim to catalyse creative partnerships, where industry partners bring complementary expertise, experience and resources to address a scientific problems or challenges brought forward by Crick researchers.”
When Sonia presented her research proposal to a team from MSD, their shared goals were immediately clear. “Our discovery research teams in London are focused on studying changes fundamental in ageing and age-related diseases, including the onset of neurodegeneration,” says Sarah Skerratt, Head of Chemistry at MSD.
“And working with clinician scientists like Sonia, there’s an obvious passion and drive from both sides to get new treatments to patients as quickly as possible.”
Sonia’s lab receives funding and support from MSD and their team of scientists with the Crick. Together, they’re building models of Parkinson’s disease using state-of-the-art stem cell technologies.
“We want to characterise different subtypes of the disease,” explains Sonia. “About 5-10% of patients have a specific genetic driver of their disease that they’ve inherited. So, by studying these individually, we can identify subtype-specific drug targets and also look for shared similarities across disease subtypes.”
Sonia grows laboratory models of different subtypes from skin cells donated by patients with Parkinson’s. She turns these into induced pluripotent stem cells, which can become any cell in the body, and then, using a technique developed with fellow Crick group leader Rickie Patani, she grows these into neurons from the midbrain, the area worst affected by Parkinson’s.
Once the models are established, researchers can probe to uncover the genetic changes and pathways behind the different forms of disease. And then look for and test new drugs.
For patients with no specific inherited driver, comparing their disease to these established models could also help match them with the treatments most likely to be effective for them.
These stem cell models allow scientists to gain a much better understanding of what happens in the human brain, explains Jill Richardson, Executive Director of Discovery Research at MSD. “For decades neurological research has been reliant on post-mortem samples, which can’t give us the information needed about how disease starts and develops, or animal models of disease, which are not a good reflection of the complexity of the human brain.
“These models are a hugely valuable research tool that other groups can use to study different aspects of the disease and drug development. It’s science of the highest quality and with the potential to change the way we approach the development of treatments for neurodegenerative conditions.”
Both Sonia and Jill believe it’s the precompetitive nature of the Crick-MSD partnership that means they can explore Parkinson’s biology with fewer limitations.
“The lack of physical boundary is also a huge benefit,” adds Jill. “When you encounter a problem or just want to brainstorm, the close proximity enables that discussion to happen more easily and is more productive.”
“Academics like to have the freedom to follow the science and make discoveries, without constraints or restrictions that can sometimes be imposed by industry funders,” explains Sonia. “But here, we have an equal partnership and aligned interests, so we can freely investigate multiple subtypes and pathways, and openly share our data and models.
“Our project may only just be starting, but we’ve already achieved much more together by combining knowledge and resources, than we would have separately.”