En español | Inside a lab in South San Francisco, not far from the airport, a small team of scientists is working on what could be a big breakthrough in treating dementia and other brain diseases.
Their focus is on fibrin, a protein involved in forming blood clots. It's great to have when you scrape your knee, but if fibrin leaks through the barrier that separates blood from the brain — as can be the case in people with dementia — it triggers a toxic level of inflammation that destroys the connections between neurons, the cells responsible for sending and receiving information. This catastrophic cascade of events leads to the cognitive decline — memory loss, confusion, difficulty thinking — that is a common feature in neurodegenerative diseases, including Alzheimer's disease and multiple sclerosis.
But neuroscientist Katerina Akassoglou has identified a way to stop the fallout from fibrin: an antibody that can block the protein from causing inflammation, without compromising fibrin's clotting abilities.
"It's not that sledgehammer approach. ... It's not a global immunosuppressant the way you see with a number of other approaches to treating inflammation,” says Dan Burgess, president and CEO of Therini Bio, the small San Francisco-based company driving Akassoglou's work forward.
And so far, things are looking promising. Akassoglou's antibody curbed brain inflammation and memory loss in Alzheimer's disease testing involving mice. Now, scientists at Therini Bio are working on a version for humans that can accomplish the same.
AARP invests in the future of dementia treatments
Therini Bio is one of several companies homing in on inflammation as a so-called target for treating dementia, which affects 50 million people worldwide. The growing interest in the approach has been part of a larger effort from researchers to cast a wider net in the search for dementia therapies after decades of failed drug trials. While there are medicines on the market that can temporarily help with the symptoms of dementia — and one that could potentially slow the progression of Alzheimer's disease, the most common form of dementia, nothing so far can reverse or cure it.
The Dementia Discovery Fund (DDF) has taken this mission to heart. The transatlantic venture capital fund invests in and creates early-stage biotech companies exploring potentially groundbreaking therapies for Alzheimer's and other dementias. In 2018, AARP invested $60 million in DDF to support its quest for dementia treatments and, ultimately, a cure.
"The need is urgent. Far too many people are affected by dementia's physical, emotional and financial burdens. And with nearly 10 million new cases each year worldwide, that number will continue to climb unless we can find safe and effective treatments,” says Scott Frisch, AARP executive vice president and chief operating officer. “AARP's investment helps to ensure that no stone is left unturned in the search for a cure.”
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Funding the Fight Against Dementia
These 18 companies in the U.S. and U.K. are currently receiving financial and other support from the Dementia Discovery Fund (DDF). AARP invested $60 million in DDF in 2018.
- Alchemab Therapeutics
- Amathus Therapeutics
- Autifony Therapeutics
- Bicycle Therapeutics
- Caraway Therapeutics
- Cumulus Neuroscience
- Evelo Biosciences
- LoQus23 Therapeutics
- Nitrome Biosciences
- Therini Bio
- Tiaki Therapeutics
- Transine Therapeutics
Source: Dementia Discovery Fund
DDF's portfolio has grown since the fund's inception in 2015. Money has been invested to now create a portfolio of 18 companies — many of which have been built from the ground up by DDF, like Therini Bio — that are working on 40 different treatment approaches for Alzheimer's disease, frontotemporal dementia, Parkinson's disease and other forms of dementia.
"I think we need to remember that dementia is not just one disease, but a term that describes a myriad of diseases with cognitive impairment,” says Laurence Barker, a partner with DDF. And treating these diseases “is going to require approaches that target multiple different areas of biology,” he adds.
For example, companies under the DDF umbrella are working on new therapeutics that aim to clear toxic components in the brain that lead to neurodegeneration, or target enzymes involved in the progression of dementia. One is hoping to change the course of diseases by manipulating RNA (ribonucleic acid), a molecule involved in protein production. Any or all could hold the answers for ending Alzheimer's and other dementias.
"In the Alzheimer's space, it's not a single disease process; it's a series of different diseases, much like cancers. And so there's unlikely to be a single agent that's going to solve Alzheimer's, right? It's going to be individualized therapies, or at least a series of therapies for different segments of the population,” Therini Bio's Burgess says.
Progress invigorates dementia researchers
There's been an uptick in interest in dementia research lately. Positive, albeit preliminary, results coming out of clinical trials have added to the energy, as has the Food and Drug Administration's recent approval of an anti-amyloid drug. Amyloid is a hallmark of Alzheimer's; some experts predict that clearing the sticky plaques it forms could be one way to keep cognition intact.
And Barker has seen this enthusiasm, firsthand: Several pharmaceutical companies, including industry giant AbbVie, have made moves this past year to collaborate with the smaller biotech firms in DDF's portfolio.
"I think it's a recognition that the science across this part of neurodegeneration is maturing, and there may be some better validated approaches here that could show benefit” in clinical trials and beyond, says Barker, who like so many on DDF's investment team has a background in medical sciences.
Burgess anticipates Therini Bio's antibody will be in clinical trials by the end of 2022. If it proves effective in curbing the brain damage brought on by dementia, it could become one more tool in the toolbox of promising treatments.
"I think it's an exciting time to be working in this space, and it's been great to see the increased interest and enthusiasm around neuroinflammation,” Burgess says. “And we think this is a novel way of approaching neuroinflammation that could be both really important on its own right and very complementary to other approaches, given the unique nature of the mechanism.”
Rachel Nania writes about health care and health policy for AARP. Previously she was a reporter and editor for WTOP Radio in Washington, D.C. A recipient of a Gracie Award and a regional Edward R. Murrow Award, she also participated in a dementia fellowship with the National Press Foundation.