New Alzheimer's drug candidate reduces toxic protein and improves memory in mice models

Data-driven models, such as Quantitative Structure Activity Relationships (QSAR), are incredibly attractive because they offer rapid methods for predicting molecular properties, including those that are difficult to access through fundamental chemical and physical theory. For new molecules, in related regions of chemical space to the training data, they can often be very accurate. The challenge is that they typically do not generalize across large diverse chemical and biological spaces. Therefore real care is needed when applying them to novel chemistry or biology. Some attempts to build more widely applicable QSAR models have been made in recent years, but most models in use today are still built for specific chemistries and properties owing to the scale and complexity of chemical space. When I started this work, especially for solubility predictions, the datasets were modest by today’s standards, often hundreds to a few thousand molecules. One of the first things that teaches you is to explore the data carefully, assess its quality and quantity, and only then move forward with modeling. The aim is to capture genuine relationships between numerical molecular descriptions and important target endpoints, but those relationships may be only locally generalizable. I also think the phrase “simple descriptors” is interesting. Some are simple, such as atom counts or bond counts, but others rely on detailed parameterization, group contributions, and graph-theoretical techniques. We still see these descriptors used today, sometimes alongside embeddings from graph neural networks or language models. The main lesson for me is that there is no single workflow. Each dataset, model, and end-use case needs careful thought.

What we're trying to do here at Benevolent is develop systems and processes that allow us to tap into the huge amount of public information and some propriety databases that we have paid to access and through that, generate hypotheses which our scientists can then triage. We've got over ten times the amount of information in our database at present (and it’s growing) than we believe that companies such as Watson have. Bringing that and filtering the signals from the ‘noise’ to our experienced drug discovery chemists and biologists, means, firstly, we can reduce the amount of time we take to triage new hypotheses, and secondly, we can develop more predictive chemical tools to allow us to make better molecules and also to reposition existing molecules for new indication.

RAS mutations are one of the most common cancer-causing genetic mutations, and the drug is now being studied in several cancer types. I think it's going to work especially well in tumors that are primarily RAS driven, including colon cancer and lung cancer. It might also work in other cancer types in combination with drugs targeting other genetic mutations, but further research is needed.

Your weight loss plan should keep you healthy and strong as you lose the extra weight. Many plans include a diet low in carbohydrates. Carb cycling is a method of optimizing your carbohydrate intake to meet your needs while dieting, fasting, and working out. When you're carb cycling, you consume carbs to meet your needs on some days and avoid them on other days. The aim of carb cycling is to consume carbohydrates when your body needs them and exclude them at other times. Such strategies in your diet plan can help your weight loss efforts. Carbohydrates, or carbs, are a significant part of the average human diet. Along with proteins and fats, they make up the bulk of your daily meals. Most carbohydrates are broken down by your body into glucose to provide energy for your cells and tissues. Carbohydrates in your diet are of three types — sugars, starches, and fiber. Sugars are simple carbs. Glucose, sugar (sucrose), lactose found in milk, and fructose found in fruits, are naturally occurring sugars. Your body metabolizes these molecules rapidly to yield energy. Starches are complex carbs. They're large molecules that consist of hundreds of molecules of simple sugars joined together. Your body needs to break them down to release energy. Starches are found in bread, potatoes, peas, corn, cereals, and pasta. Fiber is also a complex carbohydrate. Human bodies can't break down these large molecules, so they provide no energy. They're usually excreted as they are in the feces. They add bulk to your meal, so you feel full. Fiber in the diet helps avoid constipation and lowers blood sugar and cholesterol levels. Carbohydrates are an essential part of your diet. A typical diet provides 45% to 65% of its calories from carbohydrates. If you have 2,000 calories a day, you should have about 275 grams of carbohydrates. Always try to choose healthy foods for your carb intake:

More specifically, the study showed that the female patient produced very few cathelicidins, which is a natural toxin found in the immune cells of the lungs needed to fight tuberculosis. In most people infected by tuberculosis, tuberculosis bacteria attack the immune cells of the lungs. The immune cells fight the bacteria by eating them. But the tuberculosis bacterium has developed various evasive mechanisms that reduce the immune cells’ ability to digest and thus to kill the Mtb. “You could say that the tuberculosis bacterium has developed a way to lull the immune cells to sleep. This enables the disease the hide inside the immune cells, making it invisible to other parts of the immune system,” Martin Kongsbak-Wismann explains. This is where vitamin D enters the picture. Because vitamin D is able to counteract the soporific effect of the tuberculosis bacteria by making the immune cells produce more of the cathelicidin toxin. “Cathelicidin is like a microscopic needle that is able to pierce the tuberculosis bacteria. And when it does, it weakens the bacteria’s soporific effect on the immune cells. This restores the immune cells’ ability to kill tuberculosis bacteria,” says Martin Kongsbak-Wismann and adds: “We were amazed by the effect of vitamin D. In immune cells from healthy control subjects, vitamin D improved the cells’ ability to fight Mtb, whereas in the female patient’s immune cells we saw no response to vitamin D. This shows that vitamin D is key to the immune system’s ability to fight Mtb and prevent tuberculosis.” Al-Jaberi, F.A.H., et al. (2022) Reduced vitamin D-induced cathelicidin production and killing of Mycobacterium tuberculosis in macrophages from a patient with a non-functional vitamin D receptor: A case report. Frontiers in Immunology. doi.org/10.3389/fimmu.2022.1038960.