Study offers a promising new approach to stabilizing biomolecules

As an analogy, when the axon is scaled up to be the arm in a human body, you can think of the axon length in relation to the neuron's cell body as the equivalent distance from Nottingham to Paris. This significant length poses a logistical challenge for the neuron. For proteins to be expressed at the axon terminal, which is distant from the cell body, there's a requirement for translation regulation. In other words, there is a need for descentralized gene expression. Here, small non-coding RNAs play a pivotal role. Our work on microRNAs has shown their importance in spatial-temporal control of gene expression. This research aligns with the current interest in RNA biology and offers potential avenues for drug discovery, especially given the advances in RNA technologies post-covid.

Traditional cancer treatments have been largely unfocused in that they indiscriminately kill dividing cells, cancer or otherwise, which often leads to significant toxic side effects in patients. Targeted therapies on the other hand, try to inhibit one or more abnormal proteins that are found in proliferating cancer cells resulting in programmed cell death. One or more mutations in the p53 gene are found in at least 50% of all human cancers. These mutations begin a sequence of events that leads to loss of control of cell growth and proliferation. Due to its central importance in many human cancers, drugs that restore function to mutated p53 proteins have been described as one of the three holy grails of cancer research. Targeting specific abnormal proteins found only in cancer cells could be expected to be associated with less toxicity in normal healthy cells.

It has been noted in around 20 percent of the world population suffers from some form of pain or the other. In many individuals, pain may be relieved initially with pain medications, but soon tolerance develops, and there is a decrease in the efficacy of pain relievers. One of the main symptoms of IBS seen commonly in many sufferers is chronic abdominal pain. Professor Lewis said, "All pains are complex, but gut pain is particularly challenging to treat and affects around 20 percent of the world's population. Current drugs are failing to produce effective pain relief in many patients before side effects limit the dose that can be administered." Professor Brierley echoed this statement saying, "Internal organs have a complex network of sensory nerves that have a wide array of voltage-gated ion channels and receptors to detect stimuli... The hypersensitivity of these nerves in disease often contributes to the development of pain."

There are no targeted treatments approved for pancreas cancer, and we haven't had any significant progress for a long time. We've only come up with different chemotherapy combinations, and those are only moderately effective. This new treatment is staggeringly better than chemotherapy. Usually, when we think of an improvement in pancreatic cancer survival, we think of 25% improvement. This medication actually doubled survival in patients with advanced disease. We have patients who participated in the trial who are still alive, which is unheard of because the five-year survival rate for pancreatic cancer patients is only 13%-14%. If the drug is approved by the FDA, it will most likely become the new standard of care for advanced pancreatic cancer and could replace chemotherapy as a first-line treatment.

This work is going to expand greatly. We are just at the very beginning and are still trying to convince people that it is important and something that should be studied. I think that battle is over, and now the great onslaught of research is about to begin. The roles of D-amino acids, whether they are free D-amino acids or in peptides and proteins, more and more are going to be discovered. This research is going to expand greatly. I think you will find a field, D-amino acid proteomics, which we are proposing, is going to grow tremendously.