There is no still no scientific consensus on the causal mechanism of Alzheimer’s disease, or at least on the correct target for medicinal intervention – the four main contenders are:
(a) build-up of amyloid-beta fibrils
(b) build-up of tau protein tangles
(c) inflammation in the brain
(d) reaction to a virus infection
The Bad News: Last week the antibody drug “aducanumab” was withdrawn from clinical trials because of poor results – this was an anti-amyloid-beta drug. This follows other disappointing drugs aimed at amyloid-beta.
The Good News: However today there has been more positive news – a drug which has already been approved for clinical use against Hepatitis-D, called Lonafarnib, has been found to dramatically ameliorate the progress of dementia in a mouse model of the disease. The drug seems to block an enzyme (called farnesyltransferase) that facilitates the activity of the protein Rhes ultimately enhancing lysosome activity. Lysosomes are cellular waste-clearance systems that break down the toxic proteins, including tau. Research into this pathway and mechanism may open the door on further possible drugs.
Update 29th May 2019: Research published today seems to have established the mechanism by which the Herpes virus can facilitate Alzheimers. Essentially proteins from fluids within the body tend to stick to the virus surface, comprising what is termed a protein corona. It seems that there is enzymatic activity within that corona that facilitates the aggregation of amyloid plaques. It is suggested that this may not be the only causal factor leading to Alzheimers but certainly is capable of speeding up the disease process.
Update 16th Jan 2020: Research published today has shed some light on the possible mechanism leading to Alzheimers. It seems that even a little beta-amyloid will bind receptors fpr norepinephrine, a neuro-transmitter. This triggers the GSK3-beta enzyme which causes the tau tangles to become toxic, killing brain cells. This explains why the drug trials that aim to clear beta-amyloid have failed – there will always be a little left which is sufficient to trigger the critical link – GSK3-beta. The epinephrine receptor can be blocked by drugs such as idazoxan (which is already approved, but failed its clinical trials for depression treatment). Tests in mice have shown that tau build-up is indeed blocked by that drug. Independent work on blocking kinases has also implicated GSK3-beta. This holds great promise for a treatment at long last.
A new publication in Physics suggests that there may be a fifth force of nature – joining gravity, electromagnetic and strong and weak nuclear forces.
The possibility first emerged when observations of the decay of an isotope of Beryllium showed an unexplained excess of electron/positron pairs diverging from each other at a preferred angle (instead of the angle varying with the energy of the excitation of the Beryllium nucleus). The results suggested a new particle, a force-carrying boson, with a distinctive mass of 17 MeV, albeit with a tiny lifespan.
Now, experiments with excited Helium nuclei have yielded the same result.
The particle is provisionally named X17.
The new particle interacts with neutrons, which has physicists excited that the particle may be linked with the gravitational interactions of dark matter.
Two new studies have clarified that an infection with the measles virus tends toward depleting the body of B-cells – those are the cells that produce antibodies against infections that the body has previously encountered. As a result, around half of the “immune memory” is eliminated, so that, after measles, the body is again vulnerable to infection by many of the pathogens that it had previously built resistance against.
The measles vaccine does not, of course, have that effect.
It was though that Mars had no significant global magnetic field, but NASA’s InSight Mars Lander has measured the crustal field to be 20x stronger than expected from orbital measurements. Moreover, the magnetic field seems to fluctuate in direction or strength at exactly midnight (that is Mars Lander’s midnight on Mars, not ours).
The Lander has also detected an unexpected electrically conductive layer about 2.5 miles thick, way below the surface (possibly an aquifer?). All this since its landing in November 2018.
Microbiologists have reported that they have found a protein (SETD3) in humans that is essential to enable a wide range of viruses to replicate. That range includes the common cold, polio, cocksackie and viruses that cause paralysis and brain inflammation – these are all in the genus enteroviruses.
Currently we can try to counter these viruses with vaccines – very difficult when there are over a hundred different strains of common cold virus and the virus is continually evolving new strains. Or we may treat serious viral infections with anti-viral medications – but these are often expensive and the virus is free to evolve resistance to them. Thus this new discovery opens the possibility of taking a single medication that disables the human protein and stopping a large group of viruses in their tracks – they cannot evolve resistance because the medication is addressing the human protein, not one of their own. So the potential is very exciting.
However, the big question is whether disabling that human protein (albeit temporarily) would have deleterious effects on the human themself. A study in mice showed no ill-effects except that the mice had trouble giving birth because of interference with smooth muscle contraction. It is still possible the protein has other unidentified functions, and the exact method in which the virus uses the protein is still not clear, so there is much research still to be done.
A recent paper in the publication PNAS shows that the particular 20 amino-acids that are involved in life processes have a natural tendency to react together to produce peptide-bonded chains i.e. proteins. This compares with the hundreds of other possible amino-acids that do not display this natural tendency. The implication of course is that the origins of life naturally flow from chemistry rather than requiring serendipitous and rare or unusual events.
One qualification to this proposition is that the experiments only involved a subset of the bio amino-acids and more work needs to be done to demonstrate that this is a general principle for all 20 bio amino-acids. However this makes a lot of sense and it will be interesting to see if a similar principle is evident for nucleic acids.
It is possible for planets to get gravitationally ejected from a developing solar system and thenceforth wander alone through the galaxy. Current estimates are that there are a lot of these. Of course we normally think that a planet would need the energy from a sun, a star, to power any possibility of life. But a new study has raised the intriguing possibility that a supermassive black hole or Active Galactic Nuclei (AGN) gives off sufficient ultra-violet light to produce a Goldilocks zone from maybe 100 to 140 light-years from a Sag A* size AGN in where the radiation is not so severe that it would strip any atmosphere from the planet but sufficient UV would be available to power photosynthetic life. Moreover copious UV could break apart molecules to make the building blocks of life more available. The paper estimates that there could be a billion free-floating planets in the Goldilocks zone of our own galaxy.