17 December 2015
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
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
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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.
Written by Catharine
Paddock PhD
http://www.medicalnewstoday.com/articles/304212.php
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