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First Steps to Treating Dementia May Lie in Related Diseases

AARP-backed research into ALS, Alzheimer’s could lead to dementia drugs

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Eugene Mymrin / Getty Images

If there’s one thing neuroscientist Kasper Roet is feeling these days, it’s optimism.

QurAlis, the Cambridge, Massachusetts-based biotechnology company he cofounded in 2016, recently ushered two drug candidates for the treatment of amyotrophic lateral sclerosis (ALS) into early-stage clinical trials.

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Though they work in different ways — one increases levels of an important protein, the other activates a potassium channel — both therapies have the same goal: to protect against the deterioration and death of motor nerve cells in the brain and spinal cord. This hallmark of ALS leads to many of its symptoms, including muscle twitches, muscle weakness and difficulty chewing, swallowing and eventually breathing.

If all goes according to plan, the two experimental drugs could help to grow a short list of treatments available for the rare but devastating disease that affects roughly 5,000 Americans each year. There is no cure for ALS, also known as Lou Gehrig’s disease, and most people with it live only three to five years after symptoms appear, according to the National Institute of Neurological Disorders and Stroke.

Researchers hope that will soon change.

“I think we were in a different situation than we’ve been in the past,” says Roet, CEO of QurAlis, which he launched alongside two Harvard stem cell researchers and professors. “We actually understand the disease much better now.”

One thing that’s led to better understanding is the ability to study the disease in a lab dish using adult stem cell models from patients with ALS. This allowed the founders and researchers at QurAlis to pinpoint different drivers of the disease, which in most people occurs at random, and design precision therapies that target the faulty mechanisms and “bring diseased cells to a healthy state,” Roet explains. “This is really what is core for QurAlis,” he says about the company’s approach.

The potential benefits of QurAlis’ medicines could extend beyond the motor symptoms of ALS. About half the genetic mutations that can cause ALS can also cause frontotemporal dementia (FTD) and their biology is linked, Roet says. ALS and FTD are considered a spectrum disorder, and some people on that spectrum can have ALS combined with FTD to varying degrees, according to the ALS Association.

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.


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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.

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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.”

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