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Medical News Today: New drug that protects dopamine cells raises treatment hope for Parkinson’s

Researchers who tested a new drug in a mouse model of Parkinson’s disease showed it can change the behavior of immune cells so they protect dopamine-producing cells instead of attacking them.
Brain cells
The new drug achieved up to 80% protection of dopamine-producing cells in a mouse model of Parkinson’s disease.

The team – including members from the University of Nebraska Medical Center (UNMC) in Omaha and Longevity Biotech, Inc. of Philadelphia, PA – reports the findings in The Journal of Neuroscience.

Coauthor Dr. Scott Shandler, co-founder and CEO of Longevity Biotech, says:

“The results are exciting as they provide a bridge between the immune system and nerve cell protection in Parkinson’s disease.”

Senior author Howard Gendelman, a professor of pharmacology and experimental neuroscience at UNMC, says the idea for the drug was born nearly 10 years ago, when it was discovered that a type of white blood cell was attacking the brain cells that are responsible for Parkinson’s disease. He adds:

“The new Longevity Biotech drug (LBT-3627) was able to change the function of these cells from killing the nerve cells to protecting them.”

The death of dopamine-producing cells in a part of the brain called the substantia nigra pars compacta is a chief hallmark of Parkinson’s disease. Dopamine transports brain signals that control a number of functions, including movement.

As the devastating brain-wasting disease progresses, patients gradually lose their ability to walk, talk and take care of themselves.

Immune cells play key role in Parkinson’s disease

Scientists have known for a while that Parkinson’s disease involves changes to both dopamine and non-dopamine brain cells and their signaling pathways, plus inflammatory changes to microglia (innate immune cells in the central nervous system) and infiltration of T lymphocytes (a type of white blood cell in the adaptive immune system).

At first, they thought some of the changes – such as those involving the microglia and the white blood cells – were the result of injury rather than influencers of primary events. But then, nearly a decade ago, researchers discovered that both activated microglia and white blood cells play an important role in neurodegeneration in Parkinson’s disease.

The evidence from that and other studies shows the immune system can both protect and attack the brain. This has spurred much research into how to use this knowledge to produce new treatments for Parkinson’s – a disease for which there is yet no cure.

The experimental drug LBT-3627 is similar to a naturally occurring, well-established anti-inflammatory molecule called VIP that is effective in a range of disorders.

However, there have been problems with basing new drugs on VIP – one reason being it rapidly degrades in the body. Another reason is that is unable to distinguish between its two naturally intended receptors – VPAC1 and VPAC2.

Receptors are molecules that receive signals from outside the cell. They only bind to specific molecules called agonists. Drug developers use this feature to make agonist drugs that change cell behavior – in this case, to change immune cells from acting in an inflammatory to an anti-inflammatory manner.

New drug achieved 80% protection of dopamine-producing cells

LBT-3627 is different to VIP in two respects: it specifically targets only one of the receptors, VPAC2, and it appears to last much longer than VIP in the body before degrading. It also has the advantage that it could be given orally, making it more accessible to patients with Parkinson’s disease, says Dr. Shandler.

When they tested LBT-3627 in a mouse model of Parkinson’s disease, the team found it could achieve up to 80% protection of dopamine-producing cells.

The team also found that the drug had an effect on the microglia cells, and that they were ultimately responsible for the protective effect that halted the brain damage.

The developers are hoping to begin a phase 1 clinical trial of LBT-3627 in humans by 2017, after completing more preclinical tests.

Prof. Gendelman concludes:

“The key finding in our study was that a specific white blood cell subset was produced as a consequence of LBT-3627 treatment and provided protection of dopamine-producing nerve cells from being damaged. The neurotoxic immune reaction was halted and LBT-3627 was able to prevent disease.”

There are around 10 million people worldwide living with Parkinson’s disease – approximately 1 million of them in the US, where around 60,000 people are diagnosed with the disease each year.

Another hallmark of Parkinson’s disease is the accumulation and progressive spread of protein clumps called Lewy bodies in the region of the brain most affected by loss of dopamine cells. Some scientists are beginning to think the protein clumps accelerate the disease.

From a study published in The Journal of Biological Chemistry earlier this year, Medical News Today learned how researchers discovered a potential mechanism for reducing Lewy bodies that could also lead to a treatment for Parkinson’s disease.

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