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The newsletter of the Minnesota State Society of American Medical Technologists

MINNESOTA NEWS08 | 01SPRING 2018

VOLUME ISSUE

This year is ful l of educational opportuni-ties for the Great Lakes District!

SAVE THE DATES! » Great Lakes District Conference, October 5-6, 2018, in West Chester, Ohio. This will be one-and-one-half days of education, fun, and meeting with AMT members of all dis-ciplines. Watch for AMT National e-blasts in your email for more details. Mark your calendar and get that request in for your weekend off—you deserve it!

» The 80th AMT Educational Program and National Meeting is in Wash-ington, D.C., this year. The dates are July 1-5. Will there be fireworks? Yes, you will have an opportunity to see them in this beautiful city after a full day of leadership training and/or continuing education. Registration for this meeting is now online at our national website, www.americanmed-tech.org. Please be sure to check this out before May 1 to save $200 on your registration fee.

» It’s not too early to look forward to next year’s AMT Convention in Chicago, Illinois, July 1-5, 2019.

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IN THIS ISSUE ...Council lor’s Message __ 1, 3

President's Message _____ 2

Upcoming Events ________ 2

MN AMT Leadership _____ 2

Intranasal Drug Delivery Bypasses the Blood-Brain Barrier ________________3-6

Photo taken by Bobak Ha’Eri

AM

T

www.americanmedtech.org

Disclaimer: Opinions expressed in this newsletter are not necessarily reflective of those held by American Medical Tech-nologists (AMT).

Councillor’s Message

BEV CHRISTIANSEN, COUNCILLOR

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PRESIDENT/LEGISLATIVE CHAIR & EDITORClara Boykin, MT1023 Dayton Ave.St. Paul, MN 55104claraboykin1023@msn.com

VICE PRESIDENTNilam Patel, MTnilam.patelmn@yahoo.com

SECRETARY Chai Xiong, RMA

TREASURERMai Lee Yang, RMA

JOB INFORMATION/ NLW & NMAWOpen

GREAT LAKES DISTRICT COUNCILLORBev Christ iansen, RMA641-425-9809bevchristiansenrma@gmail.com

BOARD MEMBERSHeather Herring, MT, RMALesa El l iot, RMA

2017-2018 MINNESOTA AMT STATE SOCIETY LEADERSHIP

President's Message

Members of the Minnesota AMT State Society, we embark upon another year. In 2018, there will be a lot of exciting things going on in Min-nesota and overall for our organization,

including District and National meetings for all members and all disciplines.

For Minnesota AMT, we have our Collabora-tive Meeting this year in Brooklyn Center, Minne-sota, which has the theme: “Race to Excellence.” It is coming up soon: April 23-25, 2018, at the Earle Brown Center. The early-bird registration deadline is April 9, 2018.

Next, we have our National Meeting in Wash-ington, D.C., July 1-5, 2018, at the Hyatt Wash-ington on Capitol Hill; the registration fee is a great deal! But remember, the deadline to register is May 1, 2018.

We will finish 2018 with our Great Lakes Dis-trict Conference in Ohio, October 5-6, 2018.

We had our first conference call for the Great Lakes District on Tuesday, February 27, 2018. Please join in on the conference call, which we will be holding monthly as we start the year, to volunteer to be on committees. Contact me for more informa-tion. Everyone is welcome!

We are also working to schedule a Minnesota AMT State Society conference call to chat with other members in the state. Look for more informa-tion in an upcoming email blast from AMT.

I am also happy to report there will be great opportunities this year to meet all your require-ments for continuing education. If I can be of assis-tance, do not hesitate to contact me.

Clara Boykin, MT (AMT) claraboykin1023@msn.com

CLARA BOYKIN, PRESIDENT

Clinical Laboratory CollaborativeRACE TO EXCELLENCE APRIL 23-25, 2018 (Mon.-Weds.)

LOCATIONEarle Brown Heritage Center6155 Earle Brown DriveBrooklyn Center, MN 55430Early-bird registration deadline: April 9, 2018

HOTEL Embassy Suites6300 Earle Brown Dr. Brooklyn Center, MN 55430

Call 763-560-2700 to reserve your room at $125 per night. Mention the 2018 Clinical Laboratory Collaborative Meeting for the discounted rate.

Reserve by April 8 to ensure availability and rate!

UPCOMING EVENTS

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Councillor’s Message from page 1

How can you get help with your registration costs for these events? Become involved in AMT! You can attend your AMT state society meet-ings and get to know your fellow members. There are plenty of com-mittees and duties you can volunteer for. If you have a talent for writing, you may inquire about the Editor’s position in your state or merely write an article. If you would like to attend meetings, go to your state website within www.americanmedtech.org and contact the leaders in your state. If you are having trouble navigating through the page and need informa-tion, you may use the CONTACT US link in the footer on the website and send an email. You should get a response within three to five days.

You may contact AMT during regular business hours about your application, renewal, certification, CCP points, etc., at 847-823-5169 between the hours of 8 a.m. and 4 p.m. Central Time. You may also

send a fax to 847-823-0458. The AMT Office is happy to help with any issues you may have.

AMT is a nationally and inter-nationally recognized certification agency and membership society for allied health professionals. Did you know you can add “(AMT)” to your professional credentials? Share your well-earned reputation by adding the suffix “(AMT)” after your discipline-specific credential. You can see an example of this with my closing at the bottom of this message.

Before closing, I would like to thank each of the state society presi-dents in our district. Through their leadership and outstanding commu-nications, our state societies finished out another successful year. This recognition is extended to the entire officer team as well as the members of the Board of Directors. Thank you for your support of our organization, be it as a beginner or on through to a lifetime member. You do make a

difference. Each of you is needed to keep this organization great. Without each of you and the members’ passion for their profession, AMT would not flourish. We are growing, and you are the reason.

I would also like to wish Director of Education Camille Murray a happy retirement, effective March 31, 2018. Thank you for your years of service, Camille.

You may contact your state society leaders as listed on each state website page or as they are listed in this newsletter. If you have any ques-tions or concerns, we are here for our members, and wish to help in any way. I am easily reachable by text, phone, or email.

Enjoy each moment as it is and treasure your new endeavors, along with the old.

Bev Christiansen, RMA (AMT)bevchristiansenrma@gmail.com

This article is re-printed with permission from its original publisher, Neurology Reviews. It appeared in the April 2016 edition.

Intranasal Drug Delivery Bypasses the Blood-Brain Barrier By Glenn S. Williams, VP, Group Editor, Neurology Reviews

The nasal mucosa in the upper third of the nasal cavity provides a direct pathway from the external environ-ment to the brain and, according to William H. Frey II, PhD, that pathway can be used to noninvasively deliver therapeutics into the brain. This pathway effectively bypasses the blood-brain barrier and avoids the systemic exposure and side effects associated with therapeutics that enter the bloodstream. At the 19th Annual Meeting of the North American Neuromodulation Society, Dr. Frey presented an in-depth look at intranasal delivery of therapeutics to the brain.

“We have learned from experience that therapeutics sprayed into the nose or even given as nose drops can

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travel extracellularly and paracel-lularly along the olfactory axon bundles and along the trigeminal nerve pathway from the nose to the brain,” said Dr. Frey, who is Founder and Codirector of the Alzheimer’s Research Center at Regions Hospital and Senior Director of HealthPartners Neu-roscience Research in St. Paul.

Therapeutics that can be deliv-ered intranasally include proteins like insulin, small molecules, charged molecules, oligonucle-otides, therapeutic cells like stem cells and Treg cells, nanoparticles, and microparticles. “You do not have to modify your drug or thera-peutic in any way in order to do this, but this method only works for really potent therapeutics that are active in the picomolar, nano-molar, or very low micromolar con-centration range,” Dr. Frey said.

This technique is being inves-tigated in various disorders. “Most of the studies have been done in animal models, but the Alzheim-er’s work has also been done in humans,” Dr. Frey said.

THE NEUROANATO-MY OF INTRANASAL DELIVERY

The cribriform plate of the skull separates the upper part of the nasal cavity from the brain. The primary olfactory nerves are located in the roof of the nasal cavity under the cribriform plate and include the olfactory sensory neurons and odorant receptors.

Sniffing brings molecules into the nose, thus allowing them to bind to odorant receptors and send a signal. Intranasal delivery of therapeutics involves spraying therapeutics into the upper part of the nasal cavity to enable them to follow these olfactory axon bundles directly into the brain through foramena in the crib-riform plate. Once across the cribriform plate, the therapeutics penetrate the subarachnoid space and enter the perivascular spaces of the brain’s blood vessels.

When the heart pumps, a corre-sponding pulsation in the cerebro-vasculature creates a perivascular pumping mechanism that moves the therapeutics throughout the brain. “They are near the blood vessels, but on the brain side of the blood–brain barrier throughout the brain,” Dr. Frey explained. Drugs also follow the trigeminal nerves that innervate the entire nasal mucosa and follow the tri-geminal neural pathway through the trigeminal ganglion and into the brain and upper spinal cord.

“[This method] results in rapid delivery—within 10 minutes in mice, rats, and monkeys—to the brain and upper spinal cord,” Dr. Frey said. In humans, intranasal neuropeptides reach the CSF within 10 minutes. STROKE

Preclinical studies have exam-ined intranasal therapy for stroke. Researchers gave rats a stroke by

occluding the middle cerebral artery. Two hours of occlusion were followed by reperfusion. Ten minutes after the reperfusion was initiated, investigators admin-istered nose drops containing insulin-like growth factor 1—a 7,600-Da neurotrophic protein naturally found in humans. Com-pared with controls, rats that received 150 mg of this peptide intranasally had an infarct volume or amount of brain damage that was reduced by 63%. Benefit was also seen when treatment was delayed for two or four hours.

BRAIN TUMORS A different intranasal treat-

ment uses GRN163, a poly-nucleotide that inhibits the enzyme telomerase. Telomerase is expressed highly in brain tumors and is required for the brain tumor cells to keep dividing. Investiga-tors tagged the negatively charged large polynucleotide with a fluo-rescent label and administered it. They observed that GRN163 accumulated in the brain tumor over a period of four hours but did not accumulate in the normal brain. After 24 hours, GRN163 was completely cleared from the brain. Survival time was doubled following treatment with the intranasal polynucleotide.

NEURODEGENERA-TIVE DISEASE

Iron accumulates abnormally in the brain in all of the neurode-

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generative disorders. “Obviously, our bodies need iron, but the abnormal accumulation of free iron is damaging because it is a strong promoter of free-radical damage,” Dr. Frey said. Data also indicate that the key receptor for memory, the human brain muscarinic cho-linergic receptor, is rapidly inac-tivated by free iron or free heme, which are present at increased levels in the brains of people with Alzheimer’s disease. “We have a potent iron chelator, deferoxamine mesylate, that has been around for about 40 years. It has a high affinity for iron and it is a generic drug. It has been used to treat beta thalassemia, sickle cell anemia, and various conditions where too much iron is accumulated in the blood. When given intramuscu-larly over a period of two years to patients with Alzheimer’s disease, it reduced their cognitive decline by 50%. That’s a far bigger benefit than any drug on the market today for Alzheimer’s disease,” Dr. Frey noted. But there were significant side effects at the injec-tion site, and deferoxamine does not cross the blood–brain barrier well. “Consequently, we’ve been developing and have patented intranasal deferoxamine to treat Parkinson’s disease, Alzheimer’s disease, stroke, and traumatic brain injury,” Dr. Frey said.

“We’ve shown that intranasal deferoxamine protects dopamine brain cells and improves move-ment in animals with Parkinson’s

disease… We’ve shown that just a few nose drops of deferoxamine given before or after a stroke reduce brain damage in rats by 55%. We’ve shown that even in normal mice, it improves memory when given intranasally. And it also improves or reduces memory loss in Alzheimer transgenic mice.”

ALZHEIMER’S DISEASE

Fludeoxyglucose (18F) PET scans reveal adequate uptake and utilization of glucose, the main energy source for brain cells, in the brains of healthy elderly con-trols. But the brains of patients with Alzheimer’s disease do not take up glucose normally, and their brain cells consequently have less energy. “A number of areas of the brain require insulin to take up glucose, and the hippocampus is one of those areas,” Dr. Frey explained. “Insulin signaling is reduced in the brains of patients with Alzheimer’s disease, causing what some have called type 3 diabetes, or diabetes of the brain, which leaves these brain cells starved for energy and not able to function normally.”

Dr. Frey obtained several patents on the direct intranasal delivery of therapeutics, including insulin, to the brain, and various clinical trials have been con-ducted. “Four trials in patients with Alzheimer’s disease and five trials in normal, healthy adults have demonstrated improved

memory following intranasal insulin treatment, with no change in the blood levels of insulin or glucose,” Dr. Frey reported.

In one of the first trials, a single intranasal insulin treatment improved verbal memory for indi-viduals with Alzheimer’s disease within 15 minutes. In a three-week trial, intranasal insulin enhanced memory, compared with placebo, and significantly improved atten-tion and functional status in patients with Alzheimer’s disease. However, patients who carried the APOE ε4 gene allele were not improved with intranasal regular insulin. “Only long-acting insulin detemir, given intranasally, has been shown to improve memory in patients who have the APOE ε4 gene allele,” Dr. Frey said.

The longest completed trial lasted for four months and showed improved memory and func-tion in patients who were given insulin twice per day in a nasal spray. It also showed that the treat-ment reduced the loss of glucose uptake and utilization in key brain regions, as seen in PET scans. A new six-month treatment trial is now underway at the HealthPart-ners Center for Memory & Aging in St. Paul.

MECHANISM OF ACTION

One open question is whether intranasal insulin only provides symptomatic treatment (ie, improved memory and func-

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tioning in patients with Alzheim-er’s disease) or also has the poten-tial to change the underlying disease process. “We know it can provide energy to prevent brain cells from degenerating and allow the cells to produce materials to replace worn-out parts,” said Dr. Frey. “That result has been shown in humans using P-31 MRI. After administration of intra-nasal insulin, levels of brain cell adenosine triphosphate (ATP) and brain cell phosphocreatine increase significantly. We know that insulin, after it causes sig-naling, and glucose uptake occurs, causes the production of insulin-degrading enzyme to reduce the insulin signal so that the next time the signal comes in, it can be easily detected. That turns out to be the enzyme that degrades beta amyloid, which accumulates abnormally in the brains of indi-viduals with Alzheimer disease. So, if you don’t have insulin sig-naling, you don’t make insulin-degrading enzyme, and you accu-mulate beta amyloid. Insulin also inhibits glycogen synthase kinase 3 beta that phosphorylates tau to form Alzheimer neurofibrillary tangles. Insulin is also needed to maintain synaptic density, so it is possible that if humans were given intranasal insulin at the first sign of an insulin-signaling deficiency or a decrease in glucose uptake in the brain, it might be possible to delay, or maybe even prevent,

the onset of this disease,” Dr. Frey said.

STEM CELLSDr. Frey and research col-

laborators in Germany, including Lusine Danielyan, MD, discov-ered and patented that intranasal stem cells bypass the blood–brain barrier to reach the brain and treat Parkinson’s disease in rats. Adult bone marrow–derived stem cells have anti-inflammatory and neu-rotrophic properties. “After cell treatment, the proinflammatory cytokines in this inflammatory brain disease go down to normal levels. Our study showed highly significant improvement, com-pared with placebo, in motor func-tion or movement,” Dr. Frey said. Researchers in the Netherlands demonstrated that intranasal adult stem cells treat neonatal ischemia and neonatal brain damage. Other researchers at Emory University reported treat-ment of stroke with adult stem cells from bone marrow. Swedish researchers reported that intra-nasal Treg cells treat multiple scle-rosis (MS). “These studies are all in animals,” Dr. Frey noted. Other researchers reported that neu-ronal stem cells induce recovery and remyelination in an animal model of MS. Brain tumors have also been treated in animals with intranasal stem cells. Recently, intranasal stem cell therapy was also reported to improve motor

function and reduce lesion size in spinal cord injury in animals. “Noninvasive intranasal delivery can target therapeutics to the brain while reducing systemic exposure to facilitate the treatment of brain disorders,” said Dr. Frey.

References/ Suggested Reading

Danielyan L, Schäfer R, von Ameln-Mayerhofer A, et al. Therapeutic efficacy of intranasally delivered mes-enchymal stem cells in a rat model of Parkinson’s disease. Rejuvenation Res. 2011;14(1):3-16.

Danielyan L, Beer-Hammer S, Stolz-ing A, et al. Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer’s and Parkinson’s disease. Cell Trans-plant. 2014;23(suppl 1):S123-S139.

Frey WH 2nd. Noninvasive intrana-sal stem cells bypass the blood-brain barrier to target the brain to treat Parkinson’s disease, stroke, MS, brain tumors, cerebral ischemia, Alzheimer’s and other CNS disorders. J Nat Sci. 2015;1(1):e23.

Lochhead JJ, Wolak DJ, Pizzo ME, Thorne RG. Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administra-tion. J Cereb Blood Flow Metab. 2015;35(3):371-381.

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