BrightFocus Foundation grant to fund new UAB and Southern Research Alzheimer’s research

By Bob Shepard
UAB Media Relations


Research to identify a new approach to treat Alzheimer’s disease gets new funding after a pilot grant from the Alabama Drug Discovery Alliance.  

   alzheimersResearchers at the University of Alabama at Birmingham and Southern Research are launching a new study to identify a novel therapy for treating Alzheimer’s disease. Funded by a grant of $250,000 from the BrightFocus Foundation, the new study grew from preliminary work funded by the Alabama Drug Discovery Alliance.

Principal investigator Erik Roberson, M.D., Ph.D., associate professor in the Department of Neurology and co-director of the Center for Neurodegeneration and Experimental Therapeutics at UAB, and co-principal investigator Corinne E. Augelli-Szafran, Ph.D., director of the chemistry department at Southern Research, will lead this program focusing on targeting the interaction between tau and fyn, two proteins in the brain that are involved with Alzheimer’s disease.

“We’ve long known that the protein tau is associated with Alzheimer’s disease,” said Roberson. “Fyn is a protein involved in learning and memory, and has more recently been implicated in neurological conditions such as Alzheimer’s and epilepsy. There are now considerable data suggesting that blocking the interaction between tau and fyn could be protective against Alzheimer’s.”

Roberson says previous research has shown that lowering tau in the brain in animal models seems to prevent Alzheimer’s disease, and the tau/fyn linkage is an intriguing target for blocking tau’s function without having to reduce tau levels, which may be difficult in human patients.

“The interaction seems to be key,” Roberson said. “But we can test this only by finding drugs that block that interaction. The BrightFocus Foundation grant, following on the heels of our ADDA funding, will fund the next step in this process.”

The UAB School of Medicine and Southern Research began the Alabama Drug Discovery Alliance in 2008, with crucial contributions from the UAB Center for Clinical and Translational Science and the UAB Comprehensive Cancer Center. The ADDA’s objective is to use the resources available at these institutions to facilitate drug discovery and development.
The UAB School of Medicine and Southern Research began the Alabama Drug Discovery Alliance in 2008, with crucial contributions from the UAB Center for Clinical and Translational Science and the UAB Comprehensive Cancer Center. The ADDA’s objective is to use the resources available at these institutions to facilitate drug discovery and development.

“This is an excellent example of taking groundbreaking basic research to the next level, and it demonstrates the unique capabilities within the ADDA,” said Mark J. Suto, Ph.D., vice president of drug discovery at Southern Research.

The first phase of this work, funded by the ADDA, used the state-of-the-art high-throughput screening facility at Southern Research to look for compounds that acted upon the interaction of tau and fyn. More than 100,000 compounds were screened, from which about 30 compounds showed a positive response. The new grant from BrightFocus will allow the research team to further evaluate the active compounds with the goal of identifying the top two or three candidates for a potential drug that could interfere with the tau/fyn connection.

Those candidates will then be tested in animal models of Alzheimer’s disease with the ultimate goal of entering into human clinical trials for the treatment for the disease.

“This is an exciting and novel therapeutic approach for the treatment of Alzheimer’s disease,” Augelli-Szafran said. “Having been able to identify potential chemical matter from our high-throughput facility at Southern Research gives us an edge moving forward with this research program. With our drug discovery talent here at Southern Research and our research and clinical expertise at UAB, we anticipate that this program will have an impact on the Alzheimer’s disease community.”

The researchers will employ the BrightFocus Foundation grant to help support the necessary work to find the strongest contenders for a new potential drug candidate — work that got its start with the ADDA.

“This grant illustrates how we are leveraging institutional investments by both UAB and Southern Research to attract outside investment in our programs,” said Maaike Everts, Ph.D., director of the ADDA and an associate professor in the Department of Pediatrics. “I think the funding of this proposal illustrates the quality of the science and the approach we have here in the Alabama Drug Discovery Alliance, and how the strengths of both institutions complement each other, making for a very attractive partnership for external investment.”

BrightFocus Foundation is a nonprofit organization supporting research and providing public education to help eradicate brain and eye diseases, including Alzheimer’s disease, macular degeneration and glaucoma.



UAB awarded Comprehensive Stroke Center designation

By Bob Shepard
UAB Media Relations

UAB has received prestigious designation as a Comprehensive Stroke Center from the Joint Commission and American Heart Association.

stroke2“Designation as a Comprehensive Stroke Center means that UAB is prepared to offer immediate access to state-of-the-art stroke care every minute of every day.”The University of Alabama at Birmingham has been named a Comprehensive Stroke Center by the Joint Commission and the American Heart Association/American Stroke Association. UAB met the Joint Commission’s standards for Disease-Specific Care Comprehensive Stroke Center Certification. The designation means UAB is part of an elite group of providers recognized as industry leaders and responsible for setting the national agenda in highly specialized stroke care.

“Designation as a Comprehensive Stroke Center means that UAB is prepared to offer immediate access to state-of-the-art stroke care every minute of every day,” said David G. Standaert, M.D., Ph.D., professor and chair of the Department of Neurology. “We provide advanced and potentially lifesaving services that are available nowhere else in Alabama, as part of our continuing commitment to offer the best possible care to residents of our state, the surrounding region and beyond.”

Comprehensive Stroke Center certification recognizes those hospitals that have the staff, training and infrastructure to receive and treat patients with the most complex strokes. The Joint Commission recognized UAB’s advanced imaging capabilities and 24-hour availability of specialized treatments, along with staff who possess the unique education and competencies to care for complex stroke patients.

UAB, which is the first hospital with Comprehensive Stroke Center certification in Alabama, has eight expert stroke physicians and the most board-certified vascular neurologists in the state, along with 350 nurses specially trained in stroke care. UAB’s Neurosciences Intensive Care Unit is one of the largest in the United States, and UAB Hospital also boasts a dedicated stroke unit. UAB treats over 1,100 strokes a year.

UAB, which is the first hospital with Comprehensive Stroke Center certification in Alabama, has eight expert stroke physicians and the most board-certified vascular neurologists in the state, along with 350 nurses specially trained in stroke care.
“Comprehensive Stroke Center certification is a reaffirmation of the exceptional stroke care we provide for our patients,” said Mark R. Harrigan, M.D., associate professor in the Department of Neurosurgery and interim director of the UAB Comprehensive Stroke Center. “Stroke is a medical emergency, and this recognition by the Joint Commission and AHA shows that UAB is well equipped to be a leader in stroke management through education, research and enhanced patient care.”

A stroke occurs when a blood vessel either is blocked by a clot or bursts, which interrupts blood flow, depriving brain cells of the oxygen and nutrients they need to survive. An American has a stroke every 40 seconds, and someone dies from a stroke every four minutes. Strokes are the fifth-leading cause of death and the leading cause of adult disability in the U.S.

“By achieving this advanced certification, UAB has thoroughly demonstrated the greatest level of commitment to the care of its patients with a complex stroke condition,” said Mark R. Chassin, M.D., president of the Joint Commission. “Certification is a voluntary process, and the Joint Commission commends UAB for successfully undertaking this challenge to elevate the standard of its care for the community it serves.”

Comprehensive Stroke Center certification was developed in collaboration with the American Heart Association/American Stroke Association and was derived from the Brain Attack Coalition’s “Recommendations for Comprehensive Stroke Centers” and “Metrics for Measuring Quality of Care in Comprehensive Stroke Centers,” as well as on recommendations from a multidisciplinary advisory panel of experts in complex stroke care.

For more information on the Joint Commission and American Heart Association’s Advanced Certification for Comprehensive Stroke Center, visit www.jointcommission.org/ or www.heart.org/myhospital.



Teleneurology in Managing Rare Neurologic Diseases


In the United States, approximately 6% to 8% of the population, or 25 million people, have a rare disease.1,2 Currently, more than 6,800 conditions qualify as a rare disease, which, in the United States, is considered to be a condition that affects fewer than 200,000 persons.1,2 Subsequently, such diseases can be difficult to study. Single institutions often have small sample sizes and funding to conduct multicenter studies may be lacking. At a poster session during the American Academy of Neurology (AAN) 67th Annual Meeting, researchers studying progressive multifocal leukoencephalopathy caused by the JC virus, provided insights on how teleneurology might be used to improve rare disease research and the care of patients with rare diseases.1   Rare Disease Report had the opportunity to discuss the study in greater detail with the presenters, Igor J. Koralnik, MD, Division of Neuro-Immunology, Department of Neurology, and the Center for Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, MA, and Shruti P. Agnihotri, MD, a former Neuro-Infectious Diseases fellow with Dr. Koralnik at BIDMC, and now at the Division of Neuro-Immunology, Department of Neurology, The University of Alabama at Birmingham.

What is teleneurology?

Teleneurology is a form of telemedicine that uses diverse technologies to provide neurologic consultation from a distance. This might include telephone calls, e-mails, and videoconferencing. We also refer to this as cyberconsults.

What led you to provide teleneurology services? Please also describe your process.

Because we’re involved in clinical and basic research on JCV-associated diseases at BIDMC in Boston, we receive many requests for advice on such cases. We found these requests to be time-consuming, so we came up with a process for handling them more efficiently. During the academic year 2013-2014, our neuroinfectious disease fellow Dr. Agnihotri established contact with the requestor to obtain details, imaging studies, and other potentially useful information. Because we preferred to obtain the pertinent information from patients’ primary healthcare providers, if patients or their families contacted us directly, we asked them to have their treating physician contact us. Then, once all available information was obtained, Dr. Agnihotri discussed the case with Dr. Koralnik, and our recommendations were presented to patients’ treating physicians. Patients deemed to be candidates for our research studies were presented with this option, which led some patients to come to our office for a face-to-face consultation.

What kind of requests did you receive regarding JC virus syndromes and what were your findings?

We received 43 requests between July 2013 and June 2014, of which 19% originated in our home state of Massachusetts, 58% from other US states, and 23% from other countries. Based on the data we received, we identified a JC virus syndrome in 33 patients (77%) and other diseases in 8 patients (19%). We were unable to make a diagnosis in 2 cases due to insufficient data. Of the 33 patients with JC virus syndromes, 11 enrolled in our research studies. Thirteen of the 43 requests were for atypical presentations, with the majority being second opinions and inquiries related to the availability of treatment-based clinical trials.

Does teleneurology pose any challenges?

Yes, teleneurology for rare diseases presents many challenges. Ethical and legal factors require careful consideration when providing medical advice without full and direct assessment of a patient, as malpractice is always a concern. Therefore, we find it prudent to take an approach that serves to guide the referring physician, such as by describing the steps we would take to establish the diagnosis and/or determine management if we were to see a similar presentation in our clinic.

What about benefits?

There are definitely numerous benefits, including the satisfaction of providing assistance that is not available locally, access to an expanded pool of patients for research studies and publications, and grateful patients and families who may further support research through philanthropy.

Do you have a take-home message for healthcare providers with regard to teleneurology, or even telemedicine in general?

Teleneurology is an emerging field that provides considerable promise in furthering research and improving the care of patients with rare neurologic diseases; however, the process needs to be a collaborative one, with the disease expert and referring physician working closely together to reduce the challenges and enhance the benefits, particularly when a rare disease straddles several medical specialties.

References

1. Agnihotri S, Koralnik I. S.O.S. Progressive multifocal leukoencephalopathy: teleneurology for a rare disease. Poster presented at: 67th American Academy of Neurology Annual Meeting; April 18-25, 2015; Washington, DC. 2. Agnihotri S, Koralnik I. Training for a neurology career in a rare disease: the role of cyberconsults. Ann Neurol. 2015;77(5):738-740.
Image "Telecare conference" by Jackhsiao - Own work. Licensed under Public Domain via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:%E8%95%AD%E4%B8%AD%E6%AD%A3%E9%99%A2%E9%95%B7%E9%80%B2%E8%A1%8CTelecare_conference.jpg#/media/File:%E8%95%AD%E4%B8%AD%E6%AD%A3%E9%99%A2%E9%95%B7%E9%80%B2%E8%A1%8CTelecare_conference.jpg

By:  Christina T. Loguidice
Rare Diseas Report

No cure, no 'great treatments' so far for debilitating neurological condition of ataxia, say UAB doctors


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(L-R): Pelham musician and family man John Parnell is an ataxia sufferer (Tamika Moore/tmoore@al.com); Dr. Harrison Walker, a neurologist at The University of Alabama at Birmingham, diagnosed Parnell in 2013; Dr. Talene Yacoubian founded the UAB Ataxia Clinic in 2014 2013 (UAB photos).
John Parnell of Pelham, 34, plays guitar, bass and drums, has a recording studio in his house and has enjoyed a nearly lifelong love of music. "Making music in whatever form makes me happy," Parnell told AL.com in March.

But Parnell's days of playing instruments could be slowly coming to an end. He suffers from a degenerative neurological condition called ataxia that can gradually rob people of the use of their arms and legs. 

"There's a part of your brain that controls motor functions (and) it attacks that part," Parnell said. "It's like being drunk but I'm not drinking." 

"A common and debilitating symptom of ataxia is imbalance while walking, incoordination using the arms and hands during daily activities and disturbances of speech," Dr. Harrison Walker of The University of Alabama at Birmingham (UAB) Department of Neurology, who diagnosed Parnell with ataxia in 2013, told AL.com in an email.  

To find out more about ataxia -- its causes, effects, diagnosis, emotional and psychological impact, and possible treatments -- AL.com turned to Walker and Dr. Talene Yacoubian, who founded the UAB Ataxia Clinic in 2014 

What is ataxia?

As Parnell said, ataxia is a result of an attack on the brain. "Ataxia is usually due to damage or dysfunction of the cerebellum, which is found in the back of the brain," Yacoubian said in an email. 

Ataxia -- the name comes from the Greek word, "ataxis," which means "without order" or "incoordination" -- is a broad clinical term that covers a wide variety of disorders.

In fact, ataxia is not classified as a separate disease or disorder, according to the UAB neurologists.  "Ataxia is not a single disorder but a clinical description of abnormalities in coordination," Yacoubian said. "Cerebellar ataxia is a syndrome with many causes (and) is not related to a single disease," Walker said.

Many varieties, tough to diagnose

There are many different types of ataxia, and this can complicate efforts to properly diagnose it.  There are "hundreds of different causes" for cerebellar ataxia, according to Yacoubian, who said that some causes are "genetic (inherited)" and many more are "sporadic or acquired." 

Those "sporadic" causes can include stroke, multiple sclerosis, vitamin deficiencies, alcohol abuse, medication toxicities, autoimmune disorders, tumors and infections. 

Genetic causes for ataxia are "rarer," according to Yacoubian. "There are perhaps 100-200 different genes that have been associated with ataxias, but the list of gene mutations that can cause ataxia is growing rapidly due to technological advances in gene sequencing." 

Parnell's doctors at UAB are still trying to make a full and final diagnosis. "They know it's a form of genetic ataxia, but they haven't pinpointed the type I have," he said. 

Parnell takes some comfort in the fact that the ataxia will likely not kill him or impair his cognitive abilities, but he and his wife, Erin, can't be sure exactly how far the symptoms might progress. "I might end up in a wheelchair one day, but I might still have use of my arms," he said. "I might end up in a wheelchair and not have use of my arms."  

It is not uncommon for patients to face this sort of uncertainty regarding ataxia, according to Yacoubian. "Because of the huge number of possible causes of ataxia, it can take some time to determine the cause of ataxia for a patient, and sometimes we are not successful at finding the cause," she said. 

In some patients with genetic forms of ataxia, "the cause is unclear, even after extensive diagnostic testing," Walker said. 

Some non-genetic forms of ataxia are a little easier to diagnose, according to Walker.  "If the ataxia is from a structural lesion... the etiology can be determined fairly readily with imaging," he said, citing such examples as tumors and strokes. 

Early warning signs of ataxia include "Incoordination or imbalance in the legs, incoordination of the arms/hands (and) abnormal speech," Walker said. "The signs can be subtle at their onset." 

No cure, no 'great treatments'

There are, at present, no "great treatments" and no cure for ataxia, according to Walker.

"Because of the wide range of causes (of ataxia), a specific diagnosis is often difficult to determine for patients -- limiting their options for treatment," according to the Ataxia Clinic web page. 

However, "depending on the cause" of a patient's ataxia, "medications sometimes can be helpful for patients," Walker said. 

Parnell said there are, for example, drugs that can make his legs feel less heavy. However, the medicines have unpleasant side effects, such as grogginess. "I would rather suck it up and just deal with it than have to ruin my liver more than I already have," he said. 

Some days are better than others for Parnell, who already has a hard time walking. "On bad days it affects my voice (and) I talk with a slur," he said. "It hasn't affected my arms so much. I have had points where they are weak. I have points where I have what I call the shakes, the jitters." 

Emotional hardship

Ataxia comes with a significant emotional and psychological toll for the sufferers and their loved ones. In Parnell's case, that means Erin and their two-year-old daughter, Nora. 

Parnell's diagnosis -- and what he and Erin subsequently read on the Internet about the devastating effects of various forms of ataxia -- hit him hard. "Man, I won't sit here and lie," he said. "I cried." 

Because ataxia lacks a cure or effective treatments, patients "often progress and have severe disabilities that limit their mobility, their ability to work, their ability to care for family," Yacoubian said. 

"Understandably, patients with ataxia are under significant stress and often suffer from depression and anxiety," she said. "Some of the ataxias can also cause cognitive impairment that adds to the disability." 

Family members and caregivers "are also under a lot of strain and can suffer from burnout," Yacoubian said. 

Erin calls John "the very best husband and father" and said that she is up for the challenge. "I will take care of him," she said. "It is a wedding vow I will never take lightly." 

'Not an uncommon symptom'

An estimated 150,000 Americans are affected by genetic or sporadic ataxia, according to the National Ataxia Foundation.

While it is "very difficult" to estimate the number of people in Birmingham or Alabama who may have ataxia, according to Walker, he said that "it is not an uncommon neurological symptom, especially if one were to pool all of the different kinds of ataxia -- degenerative, genetic, brain tumors, strokes, multiple sclerosis -- together." 

The Ataxia Clinic is held once a month and typically sees about eight patients per clinic, according to Yacoubian. "But the clinic slots have filled up far into the future," she said. "We will probably need to hold the clinic more frequently." 

Lots of studies

Meanwhile, ataxia research is being conducted at UAB and many other places, according to Yacoubian, who recently became a member of the Clinical Research Consortium for Spinocerebellar Ataxias, a national consortium of researchers. 

Marek Napierala, a faculty member in the UAB Department of Biochemistry and Molecular Genetics, is conducting research into Friedreich's ataxia and other genetic forms, according to Yacoubian. 

There are other active studies in the Europe and the United States. Many studies are funded by the National Ataxia Foundation

'I had no idea what it was'

Parnell -- who has vowed to record and release as music as he can while he can, most of it on his own label -- wants to use his efforts to raise public awareness of ataxia. 

"The goal is to bring attention to this disease that I have and that millions have, because, to be quite honest, it's not a disease that most people know about it," he said. "I had no idea what it was until I was forced to look in the mirror and deal with it."


By Jesse Chambers | jchambers@al.com The Birmingham News 
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on April 14, 2015 at  5:14 PM, updated April 14, 2015 at  5:23 PM