Study offers potential targets for treating people with Ehlers-Danlos syndrome

The CAR positive rate is a critical metric for evaluating CAR-T product potency, directly influencing target recognition and cytotoxic efficacy. Monitoring CAR expression in peripheral blood or tissues post-infusion provides insights into in vivo expansion and persistence, informing treatment response, durability, and potential relapse risk. Dynamic CAR expression monitoring also helps assess immunogenicity and safety. Thus, a sensitive, reliable, and universal CAR detection system is vital for developing and evaluating CAR-T cell therapies. Currently, approved CAR-T products target CD19 or BCMA, making flow cytometry with recombinant BCMA or CD19 protein the standard detection method. Although highly specific, this approach is limited to single targets and is unsuitable for CAR-T screening and preclinical development. Several CAR detection methods have been developed, including Protein L (which binds immunoglobulins) or Fc-binding polyclonal antibodies. Protein L binds only to kappa light chains and fails to detect CARs containing lambda chains. Polyclonal antibodies may cross-react with patient IgG, causing false positives. Anti-idiotype antibodies offer high specificity and sensitivity by targeting unique idiotopes in the CAR's antigen-binding region, but they are challenging to develop and produce.

The bulk of vitamins and supplements containing fish oil, biotin, and vitamins A, C, and E can potentially promote nail and hair growth. You can find dietary supplements with higher concentrations of vitamins and minerals that aid skin, hair, and nail health. Fish oil supplements make nails and hair shiny. Fish oil also serves as an agent that can decrease signs of aging. If sun exposure damages the skin, the omega-3 fatty acids in fish oil can help. Biotin, also known as B7, increases hair density and strengthens it. It is found naturally in bananas, eggs, and milk. Vitamins are vital for skin health as well. Vitamin A reduces acne flairs and helps with changes due to aging like wrinkling. A vitamin A deficiency may increase the risk of acne because it becomes difficult for dead skin to slough off hair follicles, blocking pores. Vitamin B lowers the risk of precancerous growths and nonmelanoma skin cancer. Vitamin C is an antioxidant. It leads the fight against free radicals to help stimulate collagen and brighten skin. It also helps to prevent the formation of unneeded melanin that causes uneven skin pigmentation.

Leucine and isoleucine are transported into organs (including the brain) by the use of L1-neutral amino acid transporter, or LAT1. As other amino acids are also transported by LAT1, leucine and isoleucine must compete for a binding site. Amino acids imported into the brain can be used to synthesize neurotransmitters, therefore changes in amino acid concentrations may have an effect on the neurotransmitters that are made. Leucine has additional roles; it may inhibit breakdown of muscle, causes the secretion of insulin from pancreatic β-cells, as well as modulate food intake regulation through its action on the central nervous system.

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

A significant collaboration is with the Versus Arthritis Pain Center in Nottingham, in particular with Vicky Chapman and Gareth Hathway. Initially, my work wasn't focused on pain research, but joining forces with experts from this center led half of my lab's work to be directed towards pain-related projects. Another meaningful collaboration involves studying motor neuron diseases alongside Prof. Rob Layfield and Dr. Dan Scott. This collaboration allows us to leverage our expertise in RNA and neuron development and apply it to conditions like motor neuron disease.