Treatment for This Dementia Is On the Horizon
Why two experts are optimistic about research on what's known as FTD
Dr. Bruce Miller, who oversees the Memory and Aging Center at the University of California-San Francisco is a 30-year veteran — and pioneer — in diagnosing and understanding the causes of frontotemporal dementia (FTD).
That's the untreatable brain-wasting disorder that generally starts in the prime of life, alters personality, interferes with reasoning and language and leads to an early death.
Since Miller will be the keynote speaker at the Mayo Clinic's annual "Meeting of the Minds Dementia Conference" in St. Paul, Minn. on Saturday, March 1, I just spoke with him about the latest research and potential treatments for FTD. I also talked with Dr. Bradley Boeve, chair of the Mayo Clinic’s behavioral neurology department, who'll participate at the conference.
An Unusual Conference
The event, sponsored by the Alzheimer’s Association of Minnesota and North Dakota in collaboration with the Mayo Clinic, is one of the largest conferences of its kind and is unusual because it offers sessions for caregivers, patients and health care workers. I attended last year, just seven months after my wife, Liz Cummings Browning, was diagnosed with FTD. This year, I’ll cover the conference for Next Avenue and Minneapolis’ Star Tribune newspaper.
“FTD is the second-commonest dementia for people under the age of 70, and in some form probably occurs, maybe in combination, in people with Alzheimer’s disease over the age of 70,” Miller told me.
He thinks it’s an exciting time for scientists at the nation’s handful of FTD research centers, since ideas about FTD treatment are changing. “We’re starting to think very aggressively about potential therapies and have started — for the first time — multi-center, even international studies for different subtypes of frontotemporal dementias.”
FTD Causes and Types
FTD is not a disease per se, but rather, a group of disorders resulting from shrinkage of the frontal and temporal lobes of the brain. The most-common form is the behavioral variant, which results in personality changes that one of Miller’s UCSF colleagues has metaphorically referred to as identity theft.
In about 20 percent of FTD cases, patients can speak but lose the meaning of words; that's known as Semantic Dementia. An equal percentage with a form of the disorder called Primary Progressive Nonfluent Aphagia gradually lose the ability to speak.
And roughly 15 percent of FTD patients also develop Motor Neuron Disease, resulting in severe movement disorders including amylotrophic lateral schlerosis (ALS), more commonly known as Lou Gehrig’s disease.
Most of the genetic links to FTD affect people of northern European ancestry.
FTD is believed to result when proteins in the brain build up. The body is unable to remove them through its normal processes, and eventually the proteins clog up the brain, leading to cell death. This shows up on MRIs as brain shrinkage. Posotron emission tomography (PET) scans can confirm the diagnosis by graphically showing where glucose is being metabolized; inactivity indicates a region in the brain with dead or dying cells.
Miller began studying FTD while a neurology fellow at the University of California in Los Angeles and has spearheaded many breakthroughs in the diagnosis of the disorder. “I felt that it was an underdog disease and typically tragic — very tragic — for families,” he said.
These days, Miller said, he’s much more excited about emerging therapies and is optimistic that treatments are on the horizon.
Dr. Adam Boxer, one of his UCSF colleagues, is working on antibodies against the long strands of proteins known as tau (the cause of roughly 40 percent of FTD cases). Nobel laureate Stanley Pruiser, who discovered the prions responsible for Creutzfeldt-Jakob disease (CJD) — commonly known as Mad Cow Disease — is working on compounds to reduce the tau tangles. And Miller himself is conducting a small trial on a genetic form of the disorder related to the progranulin gene.
“I think the different manifestations [of FTD] have a different molecular cause,” Miller said. “The ultimate goal is to understand the molecule that is accumulating pathologically in the brain of a patient with this, and to focus on the molecule itself.”
The Next Frontier
Scientists have insights into the hereditary form of FTD but don’t understand the more common sporadic form. “I think that may be the next frontier,” Miller said.
Boeve said that if genetic factors are behind the mutations leading to the sporadic form of the disease, no one knows what they are. It’s possible that an environmental factor is the trigger. “Maybe some medications that we are currently using for other things — cholesterol, high blood pressure, common medicines – impact tau in ways that we don’t understand,” said Boeve.
New imaging techniques and research into biomarkers (telltale byproducts of the disease) may lead to earlier diagnosis that would be key to stopping or even reversing the disease before it does too much damage, noted Miller. “We saw a young person with a worry of a tau mutation and I thought to myself, 'You know, without my expectation that we’re going to treat this, this would just be unbearably hard to do.'”
Boeve said FTD researchers may find a breakthrough to treat the disorder as quickly or more quickly than Alzheimer’s because the genetic contributions are so much better known.
Tau disorders also are found in chronic traumatic encephalopathy (CTE), a dementia in the news lately because it affects athletes like National Football League players. It’s possible, Boeve said, that a single head trauma as a youngster, or a series of concussive blows over time, will trigger a mutation that leads to dementia years later.
Why FTD Can Confuse Experts
FTD research can be confusing even for the experts.
For instance, the TDP-43 protein, found in half of FTD patients, can affect the brain, the spinal cord and the nerves that exit the spinal cord, so in a family with the TDP mutation, one person may have FTD, another may have ALS and another may have both.
“And why is it? It’s the same gene, the same mutation. And yet, the area of the body where the TDP protein is depositing is different, and therefore the symptoms are different so we call it a different disorder,” Boeve said. “It’s a confusing mess.”
Even so, Boeve — like Miller — is optimistic about the future for FTD patients and their families.
“Every new gene or protein that’s found is a potential clue and may be a target for a drug that could impact other people who don’t have the genetic form,” said Boeve.