Outside the Box Thinking Brings Hope and Novel Biologics for Treating Neuro Diseases
Alzheimer's research is on a roll, with three new monoclonal antibody (mAb) drugs receiving FDA approval between 2021 and 2024. These drugs are different—unlike most treatments that manage symptoms, these next-generation drugs target the underlying disease process.
This article is posted on our Science Snippets Blog.
The Death of Neurons
Even as far back as high school biology, neurons have captivated us as some of the coolest cells. Their unique structure and function continue to fascinate and challenge scientists, especially as they work on new treatments for neurodegenerative diseases.
According to the World Health Organization (WHO), about 8.9 million people worldwide were living with Parkinson’s Disease in 2019. The numbers for Alzheimer’s are even more staggering. Of the estimated 55 million people living with dementia worldwide, 60-70% have Alzheimer’s.
These diseases happen because neurons break down over time due to toxic protein buildup. In Alzheimer’s, sticky beta-amyloid plaques and tau tangles disrupt normal brain function. In Parkinson’s, misfolded alpha-synuclein proteins disrupt communication and gradually destroy dopamine-producing neurons, which play a key role in control of movements.
This slow damage to the nervous system leads to serious issues, from memory loss to uncontrolled tremors. Science is stepping up with treatments that not only tackle symptoms but also aim to address the disease itself.
Biologics Making Waves
Antibodies that zero in on specific proteins linked to neurological conditions are key players in developing treatments for diseases like Alzheimer's and Parkinson's.
By binding to and neutralizing pathological proteins like amyloid-beta in Alzheimer's or alpha-synuclein in Parkinson's, these antibodies could potentially halt or slow down these tough neurological disorders.
To get these antibodies where they need to go, they're often paired with delivery systems like antibody-drug conjugates (ADCs) and nanoparticles to cross the blood-brain barrier.
Targeting the Disease
Popular Alzheimer's drugs mainly focus on managing symptoms and work best if you start them early. For example, cholinesterase inhibitors help with cognitive symptoms by stopping the breakdown of acetylcholine, which is key for memory and learning.
But these are just temporary fixes. The real breakthroughs happen when we can stop or even reverse the disease. That's where the newly approved biologics come in, targeting the root of the problem: amyloid beta plaques.
In 2024, the FDA gave the green light to donanemab, a monoclonal antibody that clears plaques from the brain and showed reduced cognitive decline in trials compared to a placebo. Similarly, lecanemab, approved in 2023, cut down amyloid plaques by 27% and slowed dementia.
Sometimes, new opportunities come from drugs approved for other uses. A key 2024 study published in Nature Communications revealed how two proteins, Aplp1 and Lag3, interact to let alpha-synuclein clumps into the brain. Interestingly, a melanoma drug with the anti-Lag3 antibody was found to block this interaction, stopping the spread of these Parkinson’s-causing clumps in mice.
Calling on the Immune System
Recent research in neuroimmunology is paving the way for new treatments that tap into the brain's immune system to fight Alzheimer's. These treatments aim to adjust the activity of immune cells, like microglia and T cells, which get thrown off by the disease and can't clear amyloid plaques.
The PD-1 / PD-L1 pathway is already known for helping cancer cells dodge the immune system. Immune checkpoint inhibitors targeting this interaction have significantly improved outcomes for some cancer patients by boosting T-cell function.
ImmunoBrain Checkpoint, a biopharma company, is testing a new anti-PD-L1 monoclonal antibody, IBC-Ab002, in a Phase 1b trial for early Alzheimer's. IBC-Ab002 temporarily activates the peripheral immune system to cut down on neuroinflammation and toxic protein buildup in the brain, potentially slowing cognitive decline.
Wanted: Deep Insights
The new wave of drugs targeting the brain's immune response is changing how we treat neurodegenerative diseases. Understanding these mechanisms could lead to new immunotherapies that delay symptoms and greatly improve patients' quality of life.
Developing these biologics involves high-throughput techniques to analyze disease cell biology and efficiently triage antibody candidates based on binding and mechanism of action. It's also essential to understand pharmacodynamics to ensure maximum effectiveness.
Sartorius is a leader in this field, offering cutting-edge tools that speed up biologics development and cut costs in large screenings. Check out the resources below to learn about these solutions for antibody therapeutics, including next-gen antibodies, nanobodies, and bi-specific antibodies.
