[removed]

The article I read recently explained that the NHS had agreed a different (undisclosed) amount of money for the treatment, and also explained that they balanced the cost of the drug against the cost of treating a person who then would develop the disease, and, of course, the emotional impact of a child's death. I suspect that care costs must be particularly high for this kind of treatment to be funded. Obviously I'm speaking as someone from the UK, where we don't just allow people to die if they don't have enough money to afford care. How the USA will approach this will be interesting.

[removed]

[removed]

The gene edit is not passed on to the neurons. After a bone marrow transplant, the hematopoietic stem cells can develop in different type of blood cells. Some of these can migrate into the brain, where they can either provide the missing enzyme to the neural cells, or clean up a build up of toxic compounds in the environment of the cells. In the case of MLD, it is probably this removal of toxic compounds that is beneficial.

The bone marrow transplant part is not what is new about this approval. Bone marrow transplants have been used for brain disease like MLD for a while, however a bone marrow transplant from a donor comes with a significant risk of serious complications due to rejection of the tissue. The hope is that gene editing of a patients own bone marrow cells will be much safer. In addition they can sometimes make sure that the edited gene has a higher expression, which may boost the efficacy of the transplantation.

[removed]

Oh yes thanks! I seem to have missed the bit about leukocytes being affected.

It is quite interesting that although the brain is an immune privileged site, that any resident immune cells must come from the bone marrow lymphoid lineage and presumably it is those which are tasked with clearing up the sulfatides. The black box has been resolved :)

>so a long haired orange cat would suck at blending into a jungle, get eaten or starve to death.

Tigers would beg to differ.

Many prey animals don't see orange/red as anything different that green. Green is a hard pigment for mammals to produce, but red isn't. Foxes are red, tigers are orange, and neither seem to suck at blending in vs their selected prey.

Inspired by your answer, I imagine we might also consider the fact that m1 and m2 are not perfect rigid point masses. Each is a spring-connected set of points of mass - molecules and atoms with intermolecular forces - spread in a volume. The individual points of mass will exert different gravitation forces on each other and have time-delayed spring forces transmitted through the network of points. I guess we can ignore the speed of gravity when doing a rough approximation.

[removed]

I work adjacent to this field (gene therapy), so while I do not have direct experience with MLD (the disease) nor the development of Libmeldy (the drug), I am able to peruse the data pretty well.

First, it seems clear that the cause is MLD is well-known: the deficiency of the enzyme arylsulfatase A (ARSA), which results in activity in leukocytes less than 10% of normal function. With this level of function, sulfatides build up in various tissues, eventually resulting in the destruction of the myelin sheath that is essential for nerve function. MLD is autosomal recessive, with ARSA located on chromosome 22.

So, a direct answer to your question is that since leukocytes are the cell types where the deficiency of this enzyme results in the disease state, the gene therapy which results in a new, functional version of ARSA in the stem cells which will differentiate into said leukocytes will restore efficiency of this enzyme to levels that alleviate the disease state. It would appear that restoring functionality in this specific cell type (CD34+ stem cells) is sufficient.

Some interesting notes:

The girl treated was very young, which seems to be crucial in rescuing function. Her older sister also has MLD, but her disease had progressed too far to be a candidate for the drug. Super sad and super unlucky: the parents had only a 1-in-16 chance that both of their children would have the disorder, as the parents were both carriers.

Obviously, long-term effects of this treatment are not known, as it has only recently been approved. But, researchers expect that the treatment should be lifelong because the lentivirus vector integrates into the CD34+ cells and should persist as long as that population of cells remains in the bone marrow.

The price for this drug (and other life-long gene therapy treatments) is incredibly high (in this case, I've seen 2.8 million pounds sterling quoted). This poses a number of challenges from a reimbursement standpoint, and frankly the field does not know what the best way forward is going to be. The interaction between companies, regulators, insurance, patients, etc. are all quite nuanced and the specifics differ between each of these therapies. Putting aside any ethical considerations for drugs priced this high, the actual financial logistics will always be an issue.

Hope that helped. Cheers!

[removed]

Cocaine probably, I don’t know about cathinones, but dopamine release agents do the opposite because they displace dopamine from synaptic vesicles into the cytoplasm, which is why too much meth actually kills dopamine neurons. A DRI like cocaine or methylphenidate have been shown to prevent this kind of neurotoxicity.

[removed]

[removed]

That definitely helps me grasp the idea that really we're trying to apply the closest concepts that we have, but that they're sort of just touchstones to use as you work to understand the full picture. ...Of course on some level that's true of how we understand most things in science, you work with what's good enough until it isn't any more.

[removed]

The ancestor of domestic cats is the [African wildcat] (https://en.m.wikipedia.org/wiki/African_wildcat), which still exists in the wild in Africa. There's a closely related subspecies, the Asiatic wildcat, that lives in Asia.

There are other small wild cat species, including the very similar European wildcat and the smaller sand cat.

You don't see them much because they are mostly active at night and spend a lot of their time hiding from their prey and from predators. And they're not exotic enough to make documentaries about.

In domestic cats, the tabby coloring is the most similar to their wild relatives. Other color patterns are variations that wouldn't provide adequate camouflage in the wild.

[removed]

There are wild cats that resemble house cats. Check out the "black-footed cat", one of the most effective (and adorable) predators known:

https://www.google.com/search?q=black-footed+cat&client=firefox-b-1-d&sxsrf=AJOqlzUqnL0xhxkCeBGqWWG2x-7JaseIxA:1676470670990&source=lnms&tbm=isch&sa=X&ved=2ahUKEwi03sf225f9AhUKCTQIHQQOCnQQ_AUoAXoECAEQAw&biw=1664&bih=776&dpr=1.15

The new gene (I don't think they are editing a gene, just inserting one) expresses the enzyme in the cells that were edited. These cells can lower the serum levels of sulphatides thereby reducing the levels else where in the body reducing the damage done by them and hopefully effectively curing the disease. It remains to be seen if it prevents lifelong impact from MLD.

I've always disliked the term "wave-particle duality" and I think Feynman nailed it when he said that quantum objects are neither.

>“Quantum mechanics” is the description of the behavior of matter and light in all its details and, in particular, of the happenings on an atomic scale. Things on a very small scale behave like nothing that you have any direct experience about. They do not behave like waves, they do not behave like particles, they do not behave like clouds, or billiard balls, or weights on springs, or like anything that you have ever seen. Newton thought that light was made up of particles, but then it was discovered that it behaves like a wave. Later, however (in the beginning of the twentieth century), it was found that light did indeed sometimes behave like a particle. Historically, the electron, for example, was thought to behave like a particle, and then it was found that in many respects it behaved like a wave. So it really behaves like neither. Now we have given up. We say: “It is like neither.” There is one lucky break, however—electrons behave just like light. The quantum behavior of atomic objects (electrons, protons, neutrons, photons, and so on) is the same for all, they are all “particle waves,” or whatever you want to call them. So what we learn about the properties of electrons (which we shall use for our examples) will apply also to all “particles,” including photons of light.

I would recommend the Feynman lectures for further reading.

How else would radiation raise the temperature of objects? Unless I’m fundamentally misunderstanding something, that’s energy transmission.

[removed]

Only if the accelerating twin passes through regions of lower space-time curvature (lower gravitational field).

And unless he gets in a region of negative curvature (doesn't exist in our universe as far as we know) his speed must not be too fast.