First Steps to Treating Dementia May Lie in Related Diseases

FTD — characterized by behavioral and emotional symptoms as well as movement and language problems — is one of the four main types of dementia along with Alzheimer’s disease, Lewy body dementia and vascular dementia. It impacts 50,000 to 60,000 U.S. adults and has been in headlines with the news of actor Bruce Willis’ diagnosis.

Like ALS, there is no cure for FTD. And so far, there’s no effective treatment that can stop or slow its progression.

Investing in innovative approaches

QurAlis is one of 18 active companies within the portfolio of the Dementia Discovery Fund (DDF), a venture capital fund that invests in and creates early-stage biotech companies exploring breakthrough therapies for age-related dementias. In 2018, AARP invested $60 million in DDF to support its mission in helping the more than 55 million adults worldwide affected by dementia.

“The number of Americans living with dementia continues to climb, and with it, the urgency to find effective treatments to bring relief to individuals living with dementia and their loved ones,” says Scott Frisch, AARP’s executive vice president and chief operating officer. “AARP’s investment is a reflection of our commitment to accomplishing this goal.”

Like QurAlis, other companies under the DDF umbrella are discovering dementia-causing clues and designing potential treatments. San Francisco-based Therini Bio, for example, is studying the role of fibrin in the development of dementia. Fibrin is a protein in the blood involved in forming clots, but if it leaks into the brain, it can trigger inflammation, which has been linked to cognitive decline.

Therini Bio developed an antibody that may be able to stop the inflammation without compromising fibrin’s role in clot formation. Clinical trials testing the therapeutic candidate have just begun. Alzheimer’s disease is expected to be a focus, but the drug could have applications in related diseases.

“These early investments are now starting to hit the key milestones,” says Jonathan Behr, a partner at DDF. Soon, he says, we’ll have answers as to whether these experimental therapies will turn into medicines that can help patients. “And that's really exciting,” Behr says.

Keeping the dementia drug pipeline diverse

There’s no denying that progress has been made in the past few years when it comes to dementia research, especially related to Alzheimer’s, the most common type.

Two drugs designed to slow the progression of Alzheimer’s disease, which affects more than 6 million Americans, cleared the Food and Drug Administration’s accelerated approval process, though their use in patients is restricted until additional studies confirm their effectiveness.

Both drugs, aducanumab (Aduhelm) and lecanemab (Leqembi), go after the same target in the brain — amyloid plaques, which are sticky clumps of protein that disrupt cell function. But other changes in the brain have also been linked to the onset of Alzheimer’s, including chronic inflammation and blood vessel problems. Researchers say developing therapies that target not just one but several drivers of the complex disease is key to treating all who are affected by Alzheimer’s and other forms of dementia.

“With any chronic human disease where we’ve been successful, it’s required a combination of drugs,” Behr says. Take, for example, heart disease. We have high blood pressure medications, cholesterol-lowering medications and blood-thinning medications, among others. “Each of these has a meaningful clinical benefit, but you really need to add them all together for certain patients to make a transformational difference or to halt the progression of disease,” Behr says.

The treatment landscape for ALS has advanced along with that of Alzheimer’s disease. In 2022, the FDA approved a drug that was shown in a clinical trial to help slow the progression of the disease, though larger studies are underway to better understand its effectiveness. And on April 25, regulators approved another ALS medication, this time for a small share of the patient population with a specific and rare gene mutation.

It will be a few years before researchers know if QurAlis’ precision medicines are effective in people with ALS and FTD. Behr says the hope is that if all goes well, within the next five years, the company’s treatments — and others from companies in the DDF portfolio — are in the hands of patients. Among those companies, Alector, Cerevance and Transposon Therapeutics have programs in clinical studies.

“I am very optimistic about where we are at this moment in the field,” Roet says. “I think we are understanding enough now that we think we can really make an impact.”