Amorfix Life Sciences

Ironing out misfolded proteins

Understanding just what Amorfix Life Sciences really does might require a trip back to high school biology class, but it’s worth the refresher course.

Let’s begin with the basics

Proteins are organic compounds made of amino acid strands. In order for a protein to carry out its function, the linear strand of amino acids is carefully folded into a complex three-dimensional structure as it is made in the cell. This folding process is fundamental to virtually all of biology, even though it remains a huge mystery to scientists. When proteins do not fold correctly, or “misfold”, there can be serious consequences.

“Misfolded proteins can aggregate together and form big clumps in the body,” says Dr. George Adams, CEO and Director of Amorfix. “They are toxic to the cells where they form, causing many diseases such as Alzheimer’s, Parkinson’s, multiple sclerosis (MS), diabetes, ALS, schizophrenia and many others. The challenge is distinguishing the misfolded proteins from the normal, properlyfolded proteins, and neutralizing the bad ones. That’s what Amorfix Life Sciences was created to do.”

The company is focused on tackling the serious consequences of misfolded proteins. In technical terms, Amorfix is a theranostics company dedicated to the diagnosis and treatment of Aggregated Misfolded Protein (AMP) diseases. “We identify these misfolded proteins and develop diagnostic tests,” Adams explains. “Then, we create therapies with antibodies that recognize them, grab them and neutralize them. So you end up with treatments and hopefully cures.”

Great beginnings

The company started in 2004, after a discovery was made by Dr. Neil Cashman, Amorfix co-founder and Chief Scientific Officer. He was working on a CIHR-funded Proof of Principle project when Cashman found he could detect misfolded proteins, using a special chemical. “The chemical modifies all the normal proteins in the blood so they are invisible to antibodies,” says Adams, “which makes the aggregates visible on a pitch black background. Before, it was like trying to see a star on a sunny day. This is a significant finding and was the discovery that allowed Amorfix to be formed.”

Five years later, the company has gone forward to use this technology to look for irregularities in the blood, such as the aggregated misfolded prion proteins that cause BSE and vCJD—otherwise known as Mad Cow disease (in animals and humans, respectively). “We have used the test to screen 30,000 blood donations in France and are in the final stages of validation with the UK government,” Adams beams. “Amorfix just signed a four year contract with the UK National Health Service to supply the blood screening test for transfusion purposes.”

Blood screening for misfolded proteins is also helpful in distinguishing proper treatment for patients who have AMP diseases. For example, it’s difficult to sort between people who have memory problems due to events like multiple strokes versus people who developed Alzheimer’s from protein aggregates that have accumulated in the part of the brain associated with memory.

“It can be hard to run a clinical study trial when 20 to 25 per cent of the people in a clinical trial don’t actually have a disease,” says Adams.

“One of the first advantages in finding a test for a misfolded protein is the ability to sort these patients and get a better treatment for those who do have a disease.”

Right now, Amorfix is working on three diagnostic tests (for vCJD, liver cancer and Alzheimer’s), as well as three therapeutic treatments (for ALS, Alzheimer’s and cancer). The ultimate goal is to build diagnostic tests and treatments for all AMP diseases.

“We do not see this work as a one-shot-on-goal approach,” says Adams. “Right now in the biotech industry, most people are scaling back and focusing on one thing. But we have found there is a lot of serendipity in the pharmaceutical and biotech industries. If you bet on one thing, it’s very risky. We have six projects in our pipeline. This enhances our work as one project informs the others and creates a richness of knowledge and innovative thinking in our lab. So we have a much better chance of one or more of these six will turn out to have of a lot of value.”

Plans for the future

Amorfix continues to pursue early diagnosis. “We have turned what we know about misfolded proteins into a computer program that can model and predict exactly how all 57,000 proteins misfold,” Adams reasons. “In knowing how a normal protein looks, we can now predict how likely it is to be misfolded. We identified four proteins that are known to be on the surface of cells and are likely to be misfolded. By the end of the year, we will have created antibodies to the misfolded regions our program identified and they should be both diagnostic and therapeutic.”

Adams says the market for pathogen tests for blood transfusions is a lucrative and addressable business, especially with the spread of infected cases of vCJD to hemophiliacs and MV genotype patients. Naturally, blood product suppliers and manufacturers, such as Canadian Blood Services, aim to minimize and eliminate the prion contaminants from the blood supply. The revenue earned from these contracts will be used to develop more products.

In the meantime, the company will also be working on getting its message out there. “What kills you in conventional diagnostics is all the money and time spent getting the 50,000 hospitals and private laboratories in the world to adopt your test.” In contrast, there is only one blood transfusion service per country so it is easy to get around to each of them”.

What message is it that Adams wants to convey? “We’re innovative and we now really understand protein misfolding,” he says. “On top of that, Amorfix has a great business model for generating early revenues and then using them to find cures to AMP diseases. That’s the story.”