PRESS & NEWS
FEATURED RESEARCHER: Dr. Peter Ljubenkov
Seeking a treatment to cure FTD Whether seeing patients for clinical trials or spending time with his family, Peter Ljubenkov, M.D., lives life with his heart. As a behavioral neurologist with the Memory and Aging Center at the University of California, San Francisco (UCSF), Dr. Ljubenkov specializes in caring for patients experiencing memory, language, and behavioral changes…
Seeking a treatment to cure FTD
Whether seeing patients for clinical trials or spending time with his family, Peter Ljubenkov, M.D., lives life with his heart.
As a behavioral neurologist with the Memory and Aging Center at the University of California, San Francisco (UCSF), Dr. Ljubenkov specializes in caring for patients experiencing memory, language, and behavioral changes due to neurological conditions, such as Alzheimer’s disease, Lewy body dementia, and Huntington’s disease.
His specialty is diagnosing and treating frontotemporal dementia (FTD) and related disorders, including behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD).
“I can't think of a more fascinating field” than behavioral neurology, Dr. Ljubenkov said. “It's really a field that encompasses knowledge of the basic molecular basis of how brain cells function all the way up to the more abstract ideas of human experience and how humans interact with each other.”
Neurologists diagnose and treat disorders of the brain, spinal cord, and the involuntary nervous system. There are several types, including those that focus on headaches, seizures, stroke, sleep disorders, intensive care, and movement disorders.
Behavior neurologists specialize in both basic science research to find treatments for forms of dementia and clinical trials for dementia.
“Historically, behavioral neurology was a field of neurology that was concerned with different kinds of brain functions and different parts of brain anatomy,” he explained. “What the field has grown into, particularly in the last decade or so, is a field that encompasses the spectrum of adult-onset neurodegenerative diseases and disorders that affect behavior and cognition.”
Please note that this glossary is available to help you understand the scientific terms used in this article. Glossary terms are shown in bold the first time they appear.
CAREER INFLUENCES
Like many behavioral neurologists, Dr. Ljubenkov has a personal experience with dementia. He was a caregiver prior to medical school working first as a nursing assistant in a skilled nursing facility and then for his grandfather who had developed dementia.
“Just witnessing what he went through made me particularly interested in finding a cure for people like him in the future,” the investigator said. “It was a compelling thing that I held on to all throughout med school.”
Born and raised in the Los Angeles, California, area, Dr. Ljubenkov was on the East Coast attending Temple University in Philadelphia, Pennsylvania, when his grandfather passed away.
“It was just something that I’ve carried with me throughout my career and made me really interested, not just in dementia care, but also a field of neurology that would allow me to try to find treatments for different forms of dementia,” he said.
Dr. Ljubenkov grew up in the LA neighborhood of San Pedro, a longshoreman port town. He studied neuroscience at the University of California, Santa Cruz, which is more than 350 miles up the California coast.
“I was a Banana Slug at UC Santa Cruz,” he said proudly. “That was my first real taste of Nor Cal.”
After attending the Lewis Katz School of Medicine, he returned to the West Coast for a medicine internship at the University of California, Irvine, followed by a neurology residency at the University of California, San Diego.
“It was just a brief time on the East Coast, about four years in Philadelphia, which was a great experience,” he said. “I did miss the West Coast, so it was always a goal to return to home to California.”
After finishing his residency in San Diego in 2015, he moved again from Southern California to the Bay Area in the north, more than 500 miles this time, to complete a fellowship in the behavioral neurology training program at UCSF. In 2018 he transitioned to faculty.
“UCSF is home to a world-class Memory and Aging Center and a world-class behavioral neurology fellowship program. It also is recognized as a major center for FTD research,” Dr. Ljubenkov said. “Being here is where I got my training in dementia clinical trials and then a particular interest in frontotemporal dementia.”
PERSONAL
Getting to work allows the investigator to participate in one of his greatest joys — bicycling. He has incorporated it into his daily life through his commute.
“I like bicycling in the Bay Area,” Dr. Ljubenkov said. “And yeah, I bicycle to work every day.”
While it takes about an hour, 20 minutes of his commute to UCSF is spent on a ferry crossing from the East Bay each day into San Francisco. He cycles for about 20 minutes, has a 20-minute boat ride, then cycles another 20 minutes to the Memory & Aging Center.
“It's one of the most fantastic commutes I can imagine. I love it so much,” he said. “Rain or shine, it's wonderful.”
And in the San Francisco Bay Area it rains, sometimes torrentially. At these times Dr. Ljubenkov wears special rain pants and jacket. He doesn't drive a car if he can help it.
“I tough it out in the rain,” he said. “Quite honestly, it's actually not that uncomfortable to bicycle in the rain, but only if you're properly dressed for it.”
At the end of the workday, Dr. Ljubenkov cycles home to his lovely wife and wonderful toddler. “I love being a dad,” he said.
Besides the field of neurology, his interests include the natural sciences, and he describes himself as an entomology (insect) enthusiast. He also enjoys drawing and hiking. But with a busy career and a young daughter, he doesn’t have much time for his hobbies at the moment.
“My wife and I both have busy work lives, so we like to focus on things our daughter can also enjoy during our time off,” he said. “I do still like to hike every now and then. There are some really nice low-intensity hikes all around the Bay Area, up in the hills, up in Oakland, even around Muir Woods” National Monument.
CLINICAL TRIAL RENAISSANCE
In addition to the joy he has for his family, Dr. Ljubenkov speaks exuberantly about the many clinical trials now in the field of dementia, especially FTD.
“Even outside of my work, just the sheer number of trials that have occurred in the last five years in progressive supranuclear palsy and familial forms of dementia is incredibly exciting,” he said. “I'm incredibly optimistic about it.
“I share this with my patients — it sounds hokey — but I do think we're in a renaissance of clinical trials for dementia and other adult-onset neurodegenerative diseases, including frontotemporal dementia,” he added.
He has been a clinical investigator for many, primarily industry-sponsored clinical trials.
In the last two years, Dr. Ljubenkov has initiated two separate projects of his own. One for persons with PPA and CBD with a drug called Fasudil and a new one that began recruiting this year to study the drug verdiperstat in persons with semantic variant primary progressive aphasia (svPPA).
“I am frequently the primary investigator for multiple industry trials,” he said. “I just also happen to really have a passion to design my own clinical trials and then implement them.”
ROCKIT STUDY
Rho Kinase (ROCK) Inhibitor in Tauopathies, or the ROCKIT-1 Study, is investigating a drug called Fasudil, a rho kinase (ROCK) inhibitor. The drug is owned by Woolsey Pharmaceuticals.
After enrolling 10 people diagnosed with PSP and six diagnosed with CBD, this study is no longer recruiting. It will return its primary readout this fall.
“We're hoping to discuss some of the results at the upcoming ISFTD [International Society of FTD] Conference in France,” he said, which will be held November 2-5, 2022, in Lille. “Then we’ll hopefully have our primary outcomes sometime later this year or perhaps the beginning of 2023.”
Fasudil blocks rho kinase, which is involved with tau autophagy and tau phosphorylation. The researcher said the thought was that this drug might have use in FTD types with tau pathology.
“In that particular trial we've been working closely with the group from WashU in St Louis to try
to do some innovative work looking at different types of tau biomarkers in the cerebral spinal fluid to see if those might give an indication of whether or not the drug is having a biological effect,” he explained. “That study is really exciting.”
VERI-T STUDY
More recently, Dr. Ljubenkov became the principal investigator of A Trial of Verdiperstat in Patients With svPPA Due to TDP-43 Pathology, or the Veri-T-001 Study for short. It is the first clinical trial in the United States for this cohort. It is testing the safety and tolerability of verdiperstat in persons with svPPA due to TDP-43 pathology.
“We've designed the trial to try to see an improvement in the clinical progression of functional measures and in language measures,” Dr. Ljubenkov said. “We're also looking at a host of potential biological measures of drug effect, both in the blood and in the cerebral spinal fluid (CSF).”
Veri-T is a phase 1 randomized, double-blind, placebo-controlled study. The drug or a placebo is taken by swallowing two pills twice a day for 24 weeks. One fourth of the study’s volunteers will receive the placebo, and three-fourths will receive verdiperstat.
Monthly visits are made to a study site for six months. Tests, including blood draws, MRIs, and lumbar punctures, are done before and after taking verdiperstat. A safety visit is made a month after participants stop taking the drug. There are five sites around the United States.
To be eligible, volunteers must be between 18 and 85 years of age; have a svPPA diagnosis; be willing to undergo two lumbar punctures; be able to swallow pills; and have a study partner who spends at least five hours a week with them.
Targeted enrollment is 64 people.
“I'm optimistic because verdiperstat has already been a well-studied drug in terms of its safety and tolerability,” Dr. Ljubenkov said. “It's already well known to cross into the brain when you take it orally.”
OTHER STUDIES
UCSF is “such an active trial group,” he said. “And because I'm running so many investigator-initiated trials, it's sort of hard to get everything up and running for my own studies.”
Some of the more recent studies he has overseen include:
ABBV-8E12
He was the site PI for ABBV-8E12 (tilavonemab), AbbVie Inc.’s trial of anti-tau antibodies in persons diagnosed with PSP.
INFRONT-3
He serves as the PI across all sites for INFRONT-3, Alector Inc.’s multi-center, interventional study that seeks to increase the levels of progranulin in people with a GRN gene mutation. Dr. Ljubenkov was also UCSF’s site PI for phase 1 and 2 studies of the same drug.
TPN-101
He recently became the site primary investigator for TPN-101, Transposon Therapeutics Inc.’s clinical trial that seeks to reduce the damage to nerve cells and improve the symptoms of persons diagnosed with FTD caused by a C9ORF72 mutation.
ALLFTD STUDY
Additionally, he recruits and sees patients for the ALLFTD Study, a longitudinal observational study that seeks to evaluate sporadic (s-) and familial (f-) FTLD patients, and family members of f-FTLD patients without symptoms.
Dr. Ljubenkov attributes much of the success of his career to being mentored by the leadership investigators within ALLFTD. This includes two of the three primary PIs: Adam Boxer, MD, PhD, Endowed Professor in Memory and Aging in the Department of Neurology at UCSF; and Howie Rosen, MD, the Dorothy Kirsten French Foundation Endowed Professorship for Parkinsonian and Other Neurodegenerative Disorders at UCSF.
Dr. Boxer also has served as Dr. Ljubenkov’s primary mentor since he arrived at UCSF in 2015.
MORE HATS
In addition to being a PI, Dr. Ljubenkov wears several other hats at UCSF and in the scientific community.
He has a passion for teaching in his role as an assistant professor at UCSF. He serves as the associate fellowship director of the Behavioral Neurology Training Program fellowship, which trains doctors for careers in research and clinical care involving patients with dementia.
“I really enjoy training fellows, and it’s great to be actively involved with training the next generation of behavioral neurologists,” he said.
He has also served as the medical monitor for the TauBasket trial which was an investigator-initiated trial for an anti-tau antibody in different forms of primary tauopathy.
Currently, he is the medical monitor for the Neurofilament Surveillance Project (NSP), which is a subproject of ALLFTD that is looking at how biomarkers change in the earliest stages of genetic forms of frontotemporal dementia.
Dr. Ljubenkov also manages some of the clinical training for individuals in the Global Brain Health Institute (GBHI).
“There are Atlantic Fellows for Equity in Brain Health associated with GBHI, and I'm involved with some of their clinical training,” he said.
Dr. Ljubenkov has been a member of the Boxer lab since arriving at UCSF in 2015.
He was named the 2017–2018 Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) research fellow.
In addition to all that has been mentioned, Dr. Ljubenkov is a clinician who sees patients in the UCSF memory clinic and in multiple observational research projects. The two studies he supports the most are ALLFTD and the 4 Repeat Tauopathy Neuroimaging Initiative (4RTNI). The latter is a consortium that evaluates tests — brain imaging, eye movement testing, body fluid samples, measurements of memory and other thinking abilities, and measures of functional independence — in the hope that the information can be used to guide diagnosis and treatment of PSP and CBD.
“I got in it because my heart wants for a cure,” he said. “And every day when I see patients, I want to be able to offer them something that will slow their disease or stop the disease or cure them.”
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