Page 28 - EUREKA! Summer 2018

After epilepsy and Alzheimer’s, Parkinson’s is responsible for the
third-highest healthcare costs in the country, and the debilitating

and degenerative disease will only become more prevalent and
more expensive as baby boomers age.

The green image from Matthew Holahan’s experiment shows alpha-synuclein in a mouse brain. The red image shows A-syn-1, the
aptamer he and Maria DeRosa designed to target the protein. The yellow image shows the successful co-localization of A-syn-1 and
alpha-synuclein, which has the potential to help stop Parkinson’s disease. On the opposite page, from left to right: dopaminergic
neurons in the substania nigra — part of the midbrain where Parkinson’s pathology occurs and affects motor function — are the main are optimistic, however, and after to invest in this work as the cross- while, and that takes money and time.”
source of dopamine in the brain; the motor cortex, where Holahan and DeRosa’s research is focused; and what neurodegeneration
looks under a microscope. discovering eight interesting aptamers, departmental duo continue By October, DeRosa and Holahan
including A-syn-1, they decided to file their research. plan to add new data to beef up
a provisional patent for their recipe in Holahan — whose shiny new lab on their application for a full patent, and
earlier age. lead to decreases in dopamine and to overcome the challenge of October 2017. “You synthesize millions the fifth floor of the Health Sciences because it has global market potential,
Canadian-born actor Michael J. Fox other changes throughout the body. delivering therapies across the blood- of aptamers,” says DeRosa, “and then Building has a coat of arms featuring a CITO could also file to the Patent
was only 29 when he was diagnosed “Proteins bind together and form brain barrier (BBB). This highly you have to group them into families, rat riding a mythological hippocampus Cooperation Treaty, which would
with PD in 1991. He quickly became these stringy, fibrous fibrils. That is not selective semipermeable membrane, and then you figure out patterns. There and the motto labor omnia vincit: speed up patents in national offices
a strong proponent of Parkinson’s good,” says Holahan. “That means they which protects the central nervous were eight that kept coming up. The work conquers all — wants to perform throughout the world. “We aren’t just
research, and in 1999, alongside are starting to clump together. And system from toxins and pathogens in patterns kind of matched up.” a more comprehensive study to find focused on Canadians with PD,” says
medical experts, Fox and other somewhere along the line they start the bloodstream, only admitting water out where the aptamer ends up in DeRosa. “The health of people around
celebrities with PD lobbied the U.S. to spread. Little chunks break off and and essential nutrients, also makes DeRosa and Holahan’s attempt to turn the brain and how long it stays there. the globe is at stake. But creating a
Senate for more research funding. invade other neurons, which is how it difficult to get drugs to the brain. their research into a product is the first There are dozens of “what ifs” and new technology here will lead to talent
Gerald Fischbach, at the time the a lot of neurodegenerative diseases But in recent decades, advances in project undertaken by the recently other foundational questions that need development, innovation and training
medical director of the National spread throughout the brain, kind of nanotechnology have developed a launched Carleton Innovation Transfer to be answered before human trials for the next generation of Canadian
Institute of Neurological Disorders like how a virus would infect a person delivery system using lipids — fatty Office (CITO). Carleton is an inventor- can begin. Whether their lipid-based researchers.”
and Stroke, part of the National or population. That’s the problem we acids that aren’t water soluble — that owned intellectual property institution, delivery system is the best vehicle Creating a new drug therapy is a
Institutes of Health, declared that a want to stop.” can pass through the BBB. “Getting
cure was imminent, possibly within a In 2015, DeRosa and Holahan the aptamer across to the brain is
decade. With this in mind, Fox created received an $80,000 U.S. seed grant tough,” says DeRosa. “That’s a huge
The Michael J. Fox Foundation for from The Michael J. Fox Foundation field of research in itself.”
Parkinson’s Research in 2000 and ran to explore the possibility of using an While experts still need to learn
it like an entrepreneur, taking large aptamer-based therapy to tackle the exactly how the knotted accumulation
risks for potentially great, and quick, alpha-synuclein puzzle. The startling of alpha-synuclein is linked to
results. results in Holahan’s lab occurred in dopamine loss, they know that a key
“It was my hope to build an March 2017, and a month later, when aspect of many neurodegenerative
organization fundamentally different DeRosa excitedly presented their diseases, from Alzheimer’s to
from any that presently existed,” findings on A-syn-1 to the foundation Huntington’s chorea, is a protein gone
Fox wrote in his second memoir, in New York City, they were given a six- rogue. Each culprit protein plays an
Always Looking Up. “‘We’re not month $50,000 U.S. extension. “The undetermined role in the nervous
setting up a bank,’ I told them. ‘When number of people with Parkinson’s system, and when it overproduces
money comes in, it will go back out is expected to double by 2040 to itself into clumps, nerve deterioration
immediately.’” Without an endowment, nearly 14 million worldwide,” says isn’t far behind. “Even for something
the foundation annually invests every Liliana Menalled, a senior associate like Huntington’s, where you know that which means that researchers are for the therapy and how effectively huge undertaking. It entails working
dollar it fundraises, and since its birth director of research programs at the there’s a very definitive genetic cause, usually left to their own devices. A-syn-1 performs in a larger study are with or launching a company, and
has contributed more than $800 foundation. “These individuals need it’s still questionable about how that But CITO serves as a resource for equally important queries. abiding by stringent regulations during
million U.S. to support the research therapies to prevent or stop disease gene leads to a protein malfunction faculty who want to take their ideas “The mice that we have will develop years of testing. But considering that
and development of new therapies. progression. Preventing alpha- that then leads to a disease,” says to the market. In the past year, CITO the motor symptoms as they age, but the first trials of A-syn-1 had very
Although the exact cause of PD is synuclein aggregation is a promising Holahan. “There are many different developed a commercialization plan right now we already know that alpha- promising results, DeRosa is hopeful.
unknown, its onset is associated with route toward such a treatment.” reasons why that can happen. If it was around DeRosa and Holahan’s results, synuclein is there, and we’d like to see “We gave nine injections over three
a combination of environmental and DeRosa and Holahan’s approach to clear, then we could find a cure.” found an appropriate patent agent and how it reacts to the aptamer in the months and the mice ended up with
genetic factors. In nearly every case the protein clumping is innovative, says In the event that A-syn-1 doesn’t funded the provisional patent process, brain,” says Holahan. “Then we’ll move half the aggregated protein in the
of PD, alpha-synuclein aggregates Menalled — both the aptamer itself lead to a therapy, it could still benefit which basically puts their flag on this to the next step: can you actually slow brain,” she says. “The disease had
into clumps of spaghetti-like filaments and how they have packaged it with Parkinson’s experts as a diagnostic or turf for a year. The office is currently down the disease’s progress? For that, already progressed, but with barely an
that, researchers believe, somehow fluorescent purple lipid nanoparticles research tool. DeRosa and Holahan looking for a company that’s willing you’d have to let the animals age for a intervention we saw something change.”

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