In a compelling conversation with BioPharma APAC, Dr. David Bunka, the Chief Scientific Officer (CSO) of Aptamer Group, unveils an ambitious endeavor poised to redefine the diagnostics landscape for Alzheimer's disease. This exclusive interview offers a deep dive into the collaborative initiative between Aptamer Group and Neuro-Bio, focusing on their innovative work with Optimer binders. These advanced technologies aim to tackle the significant challenges and limitations faced by current diagnostic methods for Alzheimer's, emphasizing early detection and the accuracy of diagnostics. Dr. Bunka shares insights on the potential of Optimer binders to usher in a new era of Alzheimer's diagnosis, promising a future where precise and early detection is within reach for everyone. Join us as we explore the details of this pioneering project, the science of Optimer binders, and the collective vision of Aptamer Group and Neuro-Bio in addressing one of today's most critical health challenges.

What specific challenges and limitations in current Alzheimer's diagnostics are Aptamer and Neuro-Bio aiming to overcome with the development of Optimer binders?

Currently, there are no simple, reliable diagnostic tests available for Alzheimer's disease. Physicians use a patient's medical history combined with other information, including neurological exams, cognitive and functional assessments, brain imaging (MRI, CT, PET), and cerebrospinal fluid or blood tests to make an accurate diagnosis. However, a study by the Alzheimer's Society has shown that some patients wait up to two years from referral to assessment. At this point, patients are already demonstrating the harrowing symptoms of memory loss, agitation, and mood changes. 

Neuro-Bio's approach to Alzheimer's is centred around a new disease biomarker, a peptide 'T14', that can be identified as early as 10-20 years before symptoms emerge. The Optimer binders that we develop to this new biomarker will be used in a lateral flow test, similar to the common COVID test that could act as a preliminary screen to determine whether or not you should seek further evaluation from your GP. Empowering patients with rapid early screen for Alzheimer's disease is critical to allow interventions that could prevent the onset of devastating memory loss and confusion. 

How do the properties of Optimer binders contribute to the goal of early and accurate diagnosis of Alzheimer's disease?

Optimer binders are oligonucleotide-based antibody alternatives that are developed in vitro. Aptamer Group's discovery platform allows the tuning of each binder for its specific use. This includes screening for Optimer binders to the required target and removing binders that are cross-reactive to similar proteins to ensure the specificity and accuracy of the final test. We also include the sample matrix (e.g. serum proteins, saliva proteins, etc.) in the discovery process to ensure that any identified Optimers bind to the target and not any other proteins present in the sample. This is required to improve accuracy and reduce false positive results, improving performance in the final lateral flow product. 

Lateral flow tests use pairs of binders to increase assay sensitivity. This involves two binders recognising different regions on the same protein target. Epitope dominance is one of the major problems in finding antibody pairs and happens when all the available antibodies bind to the same region of the target protein. The Optimer platform offers increased success in the generation of pairs compared to antibodies. The in vitro discovery approach of Optimer allows us to remove epitope-dominance for pair generation by using the first binder bound to the target protein as a complete target for further discovery efforts. In this way, the initial binding site is blocked by the Optimer and ensures the second Optimer binds to a site distant enough from the first to deliver a working pair.

Tuning the discovery process in this way ensures that the final Optimer binders are selective for T14 and will function in the nasal mucous assay matrix, delivering a highly accurate diagnostic assay.

Can you discuss the scalability and production advantages of Optimer binders compared to traditional methods and how this impacts the availability and cost-effectiveness of the test?

Optimer binders are highly stable, even at high temperatures, and are readily dried and rehydrated. While protein-based affinity reagents, like antibodies, are shipped on ice, we routinely ship our Optimer binders at room temperature. Also, in tests such as lateral flow tests, the reagents are commonly dried, to give a longer shelf life. This can be a problem for some antibodies that misfold and loose function when dried and rehydrated. Optimer binders don't have this problem.Not only does this cut costs and offer more environmentally friendly practices, but it also reduces waste where products have degraded through improper storage. Stability is critical to allow convenient logistics for diagnostics shipped across the globe. 

Optimer binders are synthetic molecules manufactured using readily scalable, chemical processes, without relying on biological systems like cells or animals. Consequently, the manufacturing processes are highly reproducible with minimal batch variation. Many companies around the globe can synthesise Optimer binders at various large scales through well-established, scalable processes, making these reagents easy to manufacture locally. Again, this overcomes supply chain and shipping challenges.  

What are the anticipated benefits of using a lateral flow test format for Alzheimer's diagnosis, and how does it compare to current diagnostic standards?

As mentioned the Optimer binders developed in partnership with Neuro-Bio will be used in a lateral flow test, similar to the common COVID test. This test format has been selected to enable rapid, low-cost, and convenient testing at the point of need. Patient samples can be comfortably collected and results delivered quickly, whether at the GP surgery or at home. Having such a simple, point-of-care test in place would reduce the burden on an already overloaded health system, reducing waiting times for diagnosis and the burden on patients and their families in traversing complex test procedures. 

A key benefit of Neuro-Bio's novel biomarker is that it will allow early diagnosis of Alzheimer's disease, as much as 10-20 years prior to symptoms emerging. The team at Neuro-Bio is working in parallel to develop a complementary therapy that could stabilise disease progression in diagnosed patients, ideally at the presymptomatic stage, so that patients never need develop the symptoms.

How does the collaboration between Aptamer Group and Neuro-Bio integrate their respective expertise in binder technology and neurodegenerative disease research?

We were thrilled that Baroness Greenfield immediately recognised the benefit of Optimer binders over traditional antibodies and was interested in integrating this technology into the Alzheimer's test. Neuro-Bio and Aptamer Group teams have worked closely since the project's inception to translate relevant knowledge between the companies. It's important at Aptamer Group that we understand how Neuro-Bio intends to deliver the Alzheimer's disease diagnostic test and some of the biology behind this to allow us to design the best Optimer discovery methods to provide functional binders for their lateral flow tests. 

Looking beyond Alzheimer's, do Aptamer Group and Neuro-Bio have plans to extend their collaboration to address other neurodegenerative diseases?

We love working with the team at Neuro-Bio. They are ambitious, innovative scientists with a real passion to deliver a better future for patients of Alzheimer's disease and their families. The T14 biomarker that we have developed Optimer binders to has been implicated in other biological systems and disease, such as the aging of skin, and cancer, and we would be delighted to support their work across these diverse fields with the use of Optimer binders.