Overview of the Isoelectric Point (pI)

These peptides, like the parent compound AC253, acted as antagonists at the AMY receptor. They were also resistant to protein breakdown, and crossed the blood-brain barrier easily when injected into the abdominal cavity, to localize in the hippocampus, which is crucial in memory. These peptides protected the brain against beta-amyloid injury, and normalized the AD-associated impairment of the memory-associated long-term potentiation of nerve impulses in the hippocampus. They improved memory testing results, and reduced the level of inflammation in the brain. These effects appear to be mediated via the blockade of AMY receptors. For instance, inhibition of microglial AMY receptors reduce the activation of the inflammasome NLRP3. This reduces the secretion of inflammatory chemicals in the surrounding brain tissue, which offers another mechanism for lower amyloid production. In addition, these peptides increase the rate of outflow of amyloid beta from the brain, which also contributes to a lower level of amyloid after treatment. These marked changes all occurred within a relatively short span of treatment. A very important additional finding was that treatment with these peptides brought about improvement in mice which were showing signs of well-established AD in the brain as well as in their behavior. This is unique in that most therapies fail to affect the progress of AD once it has begun to manifest clinically. Peptides also have fewer off-target effects. Small molecules are easy to administer, inexpensive to make and cross the blood-brain barrier more rapidly. For this reason, the team resorted to computational tools and artificial intelligence to come up with a new small molecular drug based on these peptides. This can be taken orally, and is similar in size and structure to the medications used for medical conditions like high blood pressure. An optimized version is being developed to enable human trials to be conducted. The work so far has taken about two decades, building step upon painstaking step to come up with the right solution. However, says Jhamandas, “Occasionally you come across a discovery that has the potential to change the game in a very fundamental way, like hitting a home run, and I'm very excited that we are really on to something here.” Short amylin receptor antagonist peptides improve memory deficits in Alzheimer’s disease mouse model. Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang & Jack Jhamandas. Scientific Reports, volume 9, Article number: 10942 (2019). https://doi.org/10.1038/s41598-019-47255-9. https://www.nature.com/articles/s41598-019-47255-9

We found that certain amino acids are elevated in cancer cells, relative to non-tumorigenic cells. This raises the question of why? This also means that they can be used as oncometabolites, which is simply something that is elevated in a cancer cell or a cancer patient, relative to what it is in a healthy person. As a diagnostic test, you can go in and if you find this oncometabolite, it is an indication that there is a cancer that needs to be examined or looked for a little more closely. So, it can be used as an early warning system, which is important.

This is a win for the field. Until now, we have been focused on immune therapies that might make tumors more vulnerable to the body's immune system, and on finding new chemotherapy combinations that kill cancer cells. This new treatment has given us a new focus, and I think it will spur a lot of scientific discovery over the next few years. There have only been a handful of KRAS researchers and their relevance to therapy was always questioned. That is about to change. The most important next step for the field is to better understand the biology of cancer. We know that many pancreatic tumors will eventually become resistant to daraxonrasib, and we need to understand how this happens. We also need to identify additional genetic pathways and treatments that can target them. That's how we will turn pancreas cancer from a deadly, deadly cancer into something we can manage-and one day, even cure.

Biologically, vitamins are absorbed within hours and have instant metabolic effects, such as antioxidants that protect cells or compounds that are building blocks for making hormones. But, many factors impact their efficiency and could keep your body from fully absorbing them. Absorption and effects depend on each individual and what combination of vitamins they take. Gender, age, digestive health, medical conditions, and diet all play a role. One helpful practice to detect deficiencies is to look for the symptoms deficiencies create. Then, look for improvement in your symptoms with supplement intake. You are unlikely to see or feel changes if you do not lack nutrients. If you are chronically tired or see signs of unhealthy nails, hair, or skin, supplements may help as these are indicators that you are lacking nutrients in your diet. If you are unsure, your doctor can order tests to check for deficiencies in your blood.

Events like ELRIG 2023 are incredibly insightful. Although I'm aware of the academia-industry interface through collaborations, for instance with Eli Lilly, attending such events on a larger scale opens up a new perspective. The goal is to bridge the gap between fundamental science academics and the broader investment realm without losing focus on the core mechanisms. By attending, I hope to identify more opportunities for collaboration and application.