Engineered stem cells show promise as drug delivery vehicle

By Wai Lang Chu

- Last updated on GMT

Scientists have found a new way to sneak drugs past the blood-brain
barrier by using stem cell derived brain cells to deliver a
critical growth factor that has already shown clinical promise for
treating Parkinson's disease.

This unique type of drug delivery approach ensures that any Parkinson's disease and other neurodegenerative disorder therapies are reaching the right place in the brain.

The team from University of Wisconsin-Madison, obtained and grew large numbers of progenitor cells from human foetal brain tissue. They then engineered the cells to produce a growth factor known as glial cell line-derived neurotrophic factor (GDNF).

Neuroscientist Clive Svendsen and his colleagues used engineered human brain progenitor cells, which were transplanted into the brains of rats and monkeys, effectively integrating them into the brain and delivering medicine where it is needed.

In clinical trials, GDNF showed a marked ability to provide relief from the debilitating symptoms of Parkinson's.

But the drug, which is expensive and hard to obtain, had to be pumped directly into the brains of Parkinson's patients for it to work, as it is unable to cross the blood-brain barrier.

Svendsen's team then implanted the GDNF secreting cells into the brains of rats and elderly primates.

The researchers found the cells migrated within critical areas of the brain and produced the growth factor in quantities sufficient for improving the survival and function of the defective cells at the root of Parkinson's

"This work shows that stem cells can be used as drug delivery vehicles in the brain,"​ said Svendsen, a professor of anatomy at the UW-Madison Waisman Centre.

In the new study, the GDNF-producing cells transplanted in the striatum of animals with a condition like Parkinson's showed not only that a critical drug could be delivered to the right place, but that the drug was delivered in a way that promoted its therapeutic potential.

The researchers reported new nerve fibre growth in the striatum and the transport of the critical nerve growth factor GDNF from the striatum to the substantia niagra, the part of the brain that harbours the cells that produce dopamine.

"In Parkinson's, the striatum loses fibres,"​ commented Svendsen. But cells in the striatum exposed to GDNF in the Wisconsin study showed an ability to recover and sprout new fibres.

"It actually seems to work better in the terminal (striatum),"​ Svendsen said. "The bonus is it gets transported back to the substantia niagra."

One hurdle that needs to be overcome before such a technique could be attempted in human patients, says Svendsen, is developing a method to switch transplanted cells on or off and thus control their drug delivery capabilities.

Working with engineered cells in culture, the Wisconsin group found they could switch the cells on and off using a second drug.

Doing so in animal models, however, was more difficult and the issue will need to be addressed in new experiments, according to Svendsen.

The new study, could prove that progenitor cells, cells that can now be made in large quantities in the laboratory, can be crafted to help clinicians deliver drugs where they are needed most in the body.

Delivering medicine to the brain, whose blood-brain barrier effectively excludes more than 70 per cent of all drugs, would be an especially valuable use for the cells.

"Such a new method may be useful for treating a number of neurodegenerative diseases beyond Parkinson's," he said.

The latest research appears in the journal Gene Therapy.

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