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Delivering drugs to the brain: New research into targeted treatment of Alzheimer's

Troy, N.Y. Pankaj Karande, a Rensselaer Polytechnic Institute assistant professor of chemical and biological engineering, is among a new generation of scientists and engineers developing exciting and novel new techniques to treat some of the most complex brain illnesses, including Alzheimer's disease, Parkinson's disease, traumatic brain injury, and brain cancer. His research has already attracted the interest of the Goldhirsh Foundation and now has garnered the support of the Alzheimer's Association with an additional $80,000 in research funding.

Karande's research seeks to open the natural and protective barriers that exist in the brain to allow for the targeted delivery of drugs into the brain. Such drug delivery systems could limit the side effects experienced by patients using existing drugs to treat brain illness, increase the effectiveness of current drug treatments, lead to the development of new drugs, and even allow drugs that previously failed in clinical trials to be reconsidered utilizing new delivery methods.

"You can have the best and most promising of drugs, but if it doesn't go where it is needed, then it won't be effective," Karande said. "There are a lot of new discoveries within the area of drug development, even related to treatment of Alzheimer's. There is not a drug discovery problem; drug delivery is really the challenge."

The problem with delivering drugs to the brain is that the brain is exceptionally good at keeping out foreign substances. The main obstacle to entry is called the blood-brain barrier. Blood vessels within the brain are lined with "Velcro-like" cells that interlock so tightly that very little is allowed to pass through into the system.

But entry is not impossible, according to Karande. "There are more blood vessels in the brain than anywhere else in the body. The supply lines are there, we simply need to understand how to open them."

Karande's hypothesis is that the key to opening these pathways into the brain can be found within the natural world. He will utilize this new research funding to investigate how certain natural pathogens cross the blood-brain barrier, and how he can develop synthetic small molecules that mimic the same blood-brain breech.

The end goal of the research is to develop small molecules that act as "chemical wedges," which "sit" on the Velcro junction points within the brain's blood vessels to prevent them from closing and gently allowing drugs to move through the system. His research seeks to develop a chemical method to open the blood-brain barrier that is gentle, but also quickly reversible.

The new technique would not be without risk, but the payoff of such a therapy would be broad, according to Karande.

"The most important challenge is going to be how we control this," he said. "We want to gently open the junctions in the brain, allow them to stay open for a short period of time during the delivery of a drug, and then reseal before any other potentially harmful materials can cross the barrier."

The result would be a much more targeted delivery of drugs to the brain. Currently, some of the most widely administered drugs used for people with brain illness do cross the blood-brain barrier, but only when large concentrations of chemicals are administered into the body to ensure that just a small fraction of the drug will bypass the tight blood-brain barrier. An example of this is the common Parkinson's drug L-DOPA, which is used to successfully treat thousands of people, but at the cost of substantial side effects due to the significant levels of the drug required to make it into the brain, according to Karande. He hopes his research success will allow drugs like L-DOPA and others to be more efficiently used within the body.

"We want to saturate the brain with a drug treatment," he said. Such saturation in the brain would reduce the presence of the drug in other healthy organs or systems and reduce side effects. It could also open up the opportunity for entirely new drugs, according to Karande.

"What is beneficial to the brain may in fact be toxic to other organs within the body," he said. "We could target just the brain with these techniques." Such targeted treatment might also allow pharmaceutical companies to reinvestigate drugs that were dropped during the drug discovery process due to toxicity to the rest of the body.

Karande will begin his research by using high-throughput cell cultures to study how different chemicals change the structure of the Velcro-like interfaces within cells. He will also continue his investigation of how different natural molecules such as the Herpes virus and bacterial toxins cross the blood-brain barrier.


Contact: Gabrielle DeMarco
Rensselaer Polytechnic Institute

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