Innovation Journeys: Stories of Invention & Discovery at UW

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AltPep

Diagnosing and Treating Amyloid Diseases

The issue

The cells in our body contain millions of large, complex protein molecules that play an important role in the structure, function, and regulation of our body’s tissues and organs. Each of these protein molecules is composed of amino acids that are connected into long chains called polypeptides. These proteins fold into unique three-dimensional structures that are determined by the sequence of amino acids found within the chain and their environment. Sometimes, these proteins unfold or misfold. This can result in the accumulation of harmful deposits that can lead to neurodegenerative and systemic disorders called amyloid diseases.

There are over 50 known amyloid diseases affecting over a billion people worldwide. Perhaps you know someone afflicted with Alzheimer’s disease (AD) or dementia. As lifespans increase, these amyloid diseases, along with many others, are reaching epidemic levels. In the U.S., a new case of AD is diagnosed every six minutes, and globally, dementia is diagnosed every three seconds.

Addressing amyloid diseases is challenging. Existing diagnostics are costly, inaccurate, and often occur decades too late. Additionally, there are few effective therapeutics; these are expensive and only offer symptomatic relief, rather than a therapeutic cure. Furthermore, amyloid diseases are often associated with multidrug-resistant bacterial infections, which can be fatal.

The spark

AltPep’s core technology is based on decades of research and discoveries from the Daggett Research Group in the Bioengineering Department at the University of Washington. Using computer modeling techniques, Valerie Daggett, Ph.D. and her team discovered that a number of amyloid proteins, all with different shapes, structures, and sequences, funneled through a non-standard, new protein structure. They hypothesized that this structure, where the amyloid proteins converged, was toxic. The structure became known as alpha-sheet.

“I fell in love with the idea of understanding how proteins move and how they exert their function. When you look at it experimentally, you kind of get one side or the other. You see it before it starts, and you see it after a process finishes. I wanted to know what was going on in between. This may sound disconnected, but it’s absolutely the thread that’s been running through my work for 30 years, and it’s what led to AltPep.”

- Valerie Daggett, PhD

Valerie Dagget Portrait

The answer

Armed with this discovery, Valerie and her team began designing and synthesizing complementary “Alternating Peptides” to neutralize the structure’s harmful toxic effects. This led to the creation of AltPep. In January 2021, AltPep raised $23.15 million in a Series A financing round to take their breakthrough amyloid targeting platform to development.

AP407 Alpha Sheet Structure
Alpha-sheet, the toxic structure discovered by Valerie and her team, where amyloid proteins converge.

How it works

AltPep has a novel approach for targeting one of the earliest players in the molecular pathology of amyloid diseases: the a-sheet-containing toxic soluble oligomers. The de novo synthetic a-sheet peptides that Valerie and her team designed provide a platform technology for selective and tailorable binding of these toxic oligomers. The technology provides pathways for imaging, screening, diagnosis, and treatment, as the peptides can be modified and refined for different disease indications and specific purposes.

The learnings

Viewing the problem through a different lens and combining multiple approaches led to Valerie’s discovery. Although AltPep is currently focused on Central Nervous System (CNS) disorders, such as Alzheimer’s disease (AD), because Valerie and her team chose to protect the intellectual property (IP) for the structure rather than composition, AltPep will be able to use the technology to address other amyloid diseases in the future.

The UW & CoMotion Boost

In this video, Valerie speaks with CoMotion Director and UW Vice Provost for Innovation, François Baneyx, about the commercialization journey she and her team have been on – the pivots, the strategies, the challenges, and successes.

CoMotion resources supporting AltPep

“CoMotion has supported us in many ways, by financially supporting individuals, getting us through that valley of death, but also early on with connecting with people in the UW Foster School of Business and the Buerk Center for Entrepreneurship.”

- Valerie Daggett, PhD

Valerie Dagget

The impact

With this technology, there is tremendous potential both to detect amyloid diseases decades earlier and to develop disease-modifying therapeutics to hinder disease development. The AltPep platform now consists of a growing library of synthetic peptides and two main company programs at this time targeting Alzheimer’s Disease:

SOBA™

To detect and track amyloid diseases

In the U.S., a new case of dementia is diagnosed every six minutes, and these diseases are not unique to the U.S. Dementia is diagnosed every three seconds worldwide and its annual global cost is estimated to exceed $1 trillion. There is an urgent need for early and accurate diagnosis of AD, which can develop undetected for 10 – 20 years. AltPep aims to change that with its plasma SOBA assay.

SOBIN™

For the early treatment of amyloid diseases

Treatment options for Alzheimer’s disease only offer symptomatic relief. AltPep’s goal is to employ its SOBA assay for early detection and its SOBIN compounds for early neutralization of the toxic oligomers to prevent irreparable damage as well as other downstream events associated with the toxic oligomers.