AI-Driven Biotech Revolution

In recent times, there have been remarkable advancements in the treatment of Alzheimer's disease.

Alzheimer's disease is a neurodegenerative condition that's associated with a gradual decline in cognitive function, memory, and ability to carry out daily activities. It's one of the most common forms of dementia. Alzheimer's is characterized by the accumulation of certain proteins in the brain that interfere with its normal function.

One of the hallmarks of Alzheimer's disease is the presence of plaques in the brain. These plaques are composed of a protein called amyloid beta (Aβ). Amyloid beta is a small piece of a larger protein called the amyloid precursor protein (APP). The APP is normally found throughout the body, but in Alzheimer's disease, it's processed in a way that forms Aβ.

The process of generating Aβ involves the activity of certain enzymes known as secretaries. These enzymes"cleave" or cut the APP into smaller pieces, one of which is Aβ.

Once formed, Aβ can exist in several different forms, such as monomers (individual molecules), oligomers (small clusters of molecules), or insoluble fibrils (long, thread-like structures). Some forms of Aβ are more prone to aggregation and plaque formation than others, meaning they're more likely to clip together and form the plaques that are characterized by Alzheimer's disease.

One such form is Aβ with a pyroglutamate modification at the N-terminus, also known as Aβp3. The N-terminus refers to one end of the protein molecule. Pyroglutamate is a modification that can occur to proteins and affect their properties, including their propensity to form aggregates or clumps.

Donanemab

In early 2024, Eli Lilly will submit "donanemab" for approval by the US Food and Drug Administration.

Donanemab is a monoclonal antibody that binds to Aβp3 and clears it from the brain. To be more detailed, Donanemab is a monoclonal antibody therapy developed by the pharmaceutical company Eli Lilly, and Co. Monoclonal antibodies are lab-created molecules that can mimic the immune system's ability to fight off harmful pathogens such as viruses.

Donanemab is designed to bind to a specific form of Aβ. Aβp3 is more prone to forming plaques. By binding to Aβp3, donanemab is thought to help clear it from the brain by reducing plaque formation and thus slowing the progression of Alzheimer's disease.

Donanemab has shown promising results in clinical trials. For instance, in the TRAILBLAZER-ALZ 2 trial, donanemab showed a 35% reduction in clinical decline, as measured by the integrated Alzheimer's Disease Rating Scale (iADRS), and a 40% improvement in the ability to perform daily activities, as measured by the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL).

Lecanemab

Lecanemab, another antibody developed by Biogen and Eisai, was granted accelerated approval by the FDA in January. Like donanemab, lecanemab is designed to bind to the Aβ and reduce its levels in the brain.

The FDA granted it accelerated approval based on its ability to lower Aβ plaques, but its clinical benefit is currently being verified in a confirmatory trial called EMBARK.

The future of drug development for neurology and cognitive disorders is looking bright.

Even more promising, Alzheimer's is the largest area being targeted by drug developers, and concerns are growing about developing disease-modifying drugs for those with dementia, neurocognitive disorders, and other related conditions.

Donanemab and lecanemab are among the first of these potential therapeutic drugs in clinical development, and with promising results, the medical community and patient populations are hopeful for the future of these treatments.

Disclaimer/warning

Some mega firms/funds (cough BlackRock) claim that after almost 2 decades, we have two drugs in the pipeline for Alzheimer's. I believe that's a misleading statement, and I think they have the financial incentive to make such a misleading claim on purpose. Donanemab phase I trial began in 2013. Giving all the credit to Artificial intelligence would be a bit of a stretch.

So, these new Alzheimer's drugs, donanemab and lecanemab, they're not exactly a walk in the park. They can have side effects that need to be watched closely. The most common one is something called ARIA, which stands for "amyloid-related imaging abnormalities." This is a fancy way of saying that there are changes in the brain that can be seen on an MRI scan.

ARIA can show up as a swelling or tiny brain bleeding spots, which can cause some real headaches (literally), confusion, or even seizures. This side effect happens more often in people with a specific genetic variant called APOE4. This particular variant is known to increase the risk of Alzheimer's and the buildup of that sticky amyloid protein we talked about earlier.

The good news is that ARIA usually sorts itself out independently or with some drug dosage adjustments. But, in some rare cases, it can be serious or even deadly.

While the development of donanemab and lecanemab is a big leap forward in Alzheimer's treatments, firms like Blackrock don't mention to back their thesis is that we can't pop the champagne just yet. These drugs are the first that may attack the root cause of the disease, not just its symptoms. But they only target one part of a very complex problem.

Other factors like tau protein tangles (another kind of sticky brain protein), inflammation, oxidative stress (damage caused by harmful molecules called free radicals), problems with the powerhouses of our cells (mitochondria), and issues with blood vessels in the brain also play a role in damaging brain cells and causing the memory loss and cognitive problems in Alzheimer's.

So, the future of Alzheimer's research needs to look at these other factors as potential targets for new treatments.

But, one of the most important things we need to remember is that early diagnosis and intervention are key. These new therapies are likely to work best if we can start them before too much damage to the brain cells has happened. So, the sooner we catch Alzheimer's, the better chance we have of slowing it down.

What's not mentioned by Blackrock is the cost and effectiveness: https://pubmed.ncbi.nlm.nih.gov/35344024/

Lecanemab is expensive, at $26,500 per year in the US. Eli Lilly has said it expects a similar price for Donanemab.

This article https://www.science.org/content/blog-post/faked-beta-amyloid-data-what-does-it-mean discusses the recent controversy surrounding doctored images in influential papers on amyloid and Alzheimer's disease.

The author provides background on the amyloid hypothesis and the history of research on Alzheimer's disease, including the failures of clinical trials attempting to turn the amyloid hypothesis into a treatment. The article also discusses the possibility of hard-to-track-down forms of amyloid as the real causative agent of Alzheimer's and the contested 2006 paper that highlighted work on a form of amyloid called AB*56.

As a neuroscience student in my Discord mentioned

"I still don't think amyloid beta is a good target.
Pharma companies have been barking up that 3 for years with almost no success. It's like putting a bandage on a leaky dam.

My guess is these Alzheimer's drugs will be another flash-in-the-pan hype drug that ends up getting shelved due to poor safety data and lacking clinical outcomes.

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Neuroscience and AI

The field of neuroscience delves into the workings of the nervous system, exploring its various functions, such as cognition, emotion, and behavior.

Neuroscience companies are businesses that apply neuroscience research to develop products and services for various domains, such as health care, education, etc.

AI is a branch of computer science that aims to create machines and systems that can perform tasks that normally require human intelligence, such as learning, reasoning, and decision-making.

AI can help neuroscience companies in many ways, such as:

• Drug R&D: AI can help discover new drugs, optimize existing ones, and reduce the cost and time of clinical trials. For example, BenevolentAI is a UK-based company that uses machine learning and natural language processing to analyze biomedical data and generate novel hypotheses for drug discovery. The company has partnered with several pharmaceutical companies to develop treatments for diseases such as Parkinson's, Alzheimer's, and cancer.
• Diagnostics: AI can help diagnose neurological disorders, predict disease progression, and monitor treatment outcomes. For example, Avalon AI is a UK-based company that uses machine learning to stratify dementia patients based on brain scans. The company claims that its technology can improve the accuracy of diagnosis by 30% and reduce the cost of clinical trials by 50%.
• Brain understanding: AI can help understand how the brain works, processes information, and interacts with the environment. For example, Neuralink is a US-based company founded by Elon Musk that aims to create brain-computer interfaces that can connect humans and machines. The company hopes to use its technology to treat neurological diseases, enhance cognitive abilities, and enable new forms of communication.

AI is transforming neuroscience and creating new opportunities for innovation and impact. However, challenges and risks are also involved, such as ethical issues, data privacy, social implications, and technical limitations. Therefore, neuroscience companies need to collaborate with researchers, regulators, customers, and stakeholders to ensure AI's responsible and beneficial use.

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Opportunity

Healthcare stocks are shares of companies that provide products and services that improve human health and well-being. They can be divided into four main categories:

• pharmaceuticals
• Medical devices
• Health insurance
• Health care facilities

Investors often view healthcare stocks as a defensive investment due to their ability to perform well despite the prevailing economic conditions.

Long-term trends, such as aging populations, increasing healthcare spending, and growing demand for innovative treatments and technologies, are also advantageous to them.

One of the most attractive segments of the healthcare sector is biotechnology, which involves the use of biological processes to develop drugs, vaccines, diagnostics, and therapies for various diseases and conditions.

Biotechnology stocks have been outperforming the broader market in recent years, thanks to the rapid pace of scientific discovery and the emergence of new areas such as gene editing, immunotherapy, and neuroscience. Biotechnology stocks also offer exposure to artificial intelligence (AI), which is transforming the way drugs are discovered, developed, and delivered.

BlackRock Health Sciences Trust (BME) invests in a diversified portfolio of healthcare stocks across different regions, sectors, and market capitalizations. The fund focuses on companies that have strong growth potential, attractive valuations, and competitive advantages in their respective fields.

Some of the fund's top holdings include Novo Nordisk (NVO), a Danish company that specializes in diabetes care; Thermo Fisher Scientific (TMO), a U.S. company that provides instruments, equipment, and services for scientific research and analysis; and Roche Holding (RHHBY), a Swiss company that is a global leader in oncology, immunology, and diagnostics.

Healthcare stocks may offer attractive opportunities for long-term investors who are looking for growth, income, and diversification. Healthcare stocks might be more resilient to macroeconomic shocks and geopolitical uncertainties as they are driven by secular trends that are independent of the business cycle.

Sources: https://www.iqvia.com/insights/the-iqvia-institute/reports/global-trends-in-r-and-d-2022

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