Fight Aging!

Autoimmune conditions such as multiple sclerosis can be cured by clearing the entire adult immune system and letting it reestablish itself. The misconfigurations of autoimmunity are carried by some immune cells, and removing all of them happens to be the easiest way to proceed in the absence of knowing exactly where the problem lies. This is currently a fairly risky and unpleasant procedure, akin to chemotherapy. Future improvement might involve less toxic means of removing immune cells, or a more targeted approach enabled by a greater understanding of exactly which immune cells cause autoimmunity. Given a good enough understanding of the mechanisms involved, it should be possible to solve the problem by changing cell state and behavior rather than destroying cells. The latter approach is in evidence here, in which researchers demonstrate reversal of autoimmunity in a mouse model of multiple sclerosis - though there remains a way to go in order to explain exactly what is going on under the hood.

While autoimmune diseases are largely not age-related, there is certainly a great deal of dysfunction in the aging immune system that might be eliminated by destroying all immune cells, or only some of the errant immune cells that cause such issues, or by altering their state and behavior. That list runs in order of difficulty: destroying all cells is a lot easier than the other options, especially given the gaps in knowledge that still exist when it comes to the immune system and aging. It nonetheless seems likely that the treatment of autoimmune conditions is where new technologies will emerge that can form the basis for therapies capable of turning back some of the aspects of age-related immune system failure. It is worth keeping an eye on this part of the field.

Multiple sclerosis can be inhibited or reversed using a novel gene therapy technique that stops the disease's immune response in mouse models. By combining a brain-protein gene and an existing medication, the researchers were able to prevent the mouse version of multiple sclerosis. Likewise, the treatments produced near-complete remission in the animal models. Multiple sclerosis starts when the immune system attacks the myelin sheath surrounding nerve fibers, making them misfire and leading to problems with muscle weakness, vision, speech and muscle coordination.

The researchers used a harmless virus, known as an adeno-associated virus, to deliver a gene responsible for a brain protein into the livers of the mouse models. The virus sparked production of so-called regulatory T cells, which suppress the immune system attack that defines multiple sclerosis. The gene was targeted to the liver because it has the ability to induce immune tolerance. "Using a clinically tested gene therapy platform, we are able to induce very specific regulatory cells that target the self-reactive cells that are responsible for causing multiple sclerosis."

The protein, myelin oligodendrocyte glycoprotein, was found to be effective in preventing and reversing muscular dystrophy on its own. A group of five mouse models that received the gene therapy did not develop experimental autoimmune encephalomyelitis, which is the mouse equivalent of multiple sclerosis in humans. In another experiment, all but one mouse model showed a significant reversal of the disease eight days after a single gene therapy treatment. After seven months, the mouse models that were treated with gene therapy showed no signs of disease, compared with a group of untreated mouse models that had neurological problems after 14 days.

When the protein was combined with rapamycin - a drug used to coat heart stents and prevent organ transplant rejection - its effectiveness was further improved, the researchers found. The drug was chosen because it allows helpful regulatory T-cells to proliferate while blocking undesirable effector T-cells. Among the mouse models that were given rapamycin and the gene therapy, 71 percent and 80 percent went into near-complete remission after having hind-limb paralysis. That shows the combination can be especially effective at stopping rapidly progressing paralysis. While researchers have established how gene therapy stimulates regulatory T cells in the liver, little else is known about the detailed mechanics of how that process works. Before the therapy can be tested in humans during a clinical trial, further research involving other preclinical models will be needed. Researchers also need to target the full suite of proteins that are implicated in multiple sclerosis.

Link: http://news.ufl.edu/articles/2017/09/unique-gene-therapy-prevents-reverses-multiple-sclerosis-in-animal-model.php