Fight Aging!

For more than twenty years now, Richard Burt's research teams have been working on the treatment of autoimmunity through the destruction and recreation of the immune system. Autoimmunity is a malfunction in the self-tolerance of immune cells, leading them to attack patient tissues. The malfunction is entirely contained in the immune system, so if the immune system is destroyed and replaced, the autoimmunity stops. If the genesis of autoimmunity is happenstance, an unfortunate one-time accident, then this is a cure. But if autoimmunity has a trigger outside the immune system in a given patient, it will return after some period of time.

The major autoimmune conditions are not well enough understood to be able to confidently point at specific causes. Some are clearly still umbrella categories, descriptions of symptoms and end states waiting to be split apart into a better taxonomy of disease based on underlying causes. It is not possible to make sensible statements as to the degree to which any given condition falls into one or other of the categories above, a one-time accident versus a continued triggering cause. We can only make educated guesses. In the ten years since Burt's group carried out a trial of immune destruction and recreation in type 1 diabetes patients, the data has shown that remission from the condition lasted a median 3.5 years. Thus type 1 diabetes appears largely a condition that has a lasting trigger. Or, we could argue that the approach used at the time failed to kill enough immune cells; some survived to spread their malfunction once more.

Another interesting question is whether the malfunction occurs in the periphery, among mature immune cells, or in the hematopoietic stem cells that generate all immune cells. In either case different strategies might result. The present incarnation of Burt's approach involves hematopoietic stem cell transplant (HSCT) coupled with chemotherapeutic ablation of existing peripheral immune cells, so it covers all of the bases. It is a harsh therapy for patients, with a meaningful risk of death - it only makes sense for the worst cases, those facing death and grave disability without intervention. Given more selective, more gentle cell killing technologies, such as Oisin Biotechnologies' programmable suicide gene therapy, much better treatments might be built, and all autoimmunity controlled.

This is an important line of research and development, as a clean recreation of the immune system would also solve a great deal of the decline and dysfunction that arises with aging, clearing out misconfigured and damaged cells of many different varieties. It would solve all of the problems that the research community does not currently understand, as well as those identified and catalogued. Burt's work should be considered prologue to a future of immune recreation carried out using much more advanced technologies. It points the way.

For some multiple sclerosis patients, knocking out the immune system might work better than drugs

In multiple sclerosis (MS), a disease that strips away the sheaths that insulate nerve cells, the body's immune cells come to see the nervous system as an enemy. Some drugs try to slow the disease by keeping immune cells in check, or by keeping them away from the brain. But for decades, some researchers have been exploring an alternative: wiping out those immune cells and starting over. The approach, called hematopoietic stem cell transplantation (HSCT), has long been part of certain cancer treatments. A round of chemotherapy knocks out the immune system and an infusion of stem cells - either from a patient's own blood or, in some cases, that of a donor - rebuilds it. The procedure is already in use for MS and other autoimmune diseases at several clinical centers around the world, but it has serious risks and is far from routine. Now, new results from a randomized clinical trial suggest it can be more effective than some currently approved MS drugs.

Nearly 30 years ago, when hematologist Richard Burt saw how HSCT worked in patients with leukemia and lymphoma, he was struck by a curious effect: After those patients rebuilt their immune systems, their childhood vaccines no longer protected them. Without a new vaccination, the new immune cells wouldn't recognize viruses such as measles and mumps and launch a prompt counterattack. That suggested that in the case of an autoimmune disease, reseeding the immune system might help the body "forget" that its own cells were the enemy.

Burt and others have since used HSCT for a variety of autoimmune diseases, including rheumatoid arthritis and lupus. In the past few years, several teams have reported encouraging results in MS. But only one study - which evaluated just 17 patients - directly compared HSCT to other available drug treatments. In the new trial, Burt and his colleagues recruited 110 people with the most common form of MS, known as relapsing-remitting. In that form of the disease, patients can go long periods without symptoms - which include muscle weakness and vision problems - before inflammation flares up. Trial participants had at least two such relapses in the previous year, despite being on one of several approved MS drugs.

Half the participants continued with drug treatment but switched from a drug that wasn't working for them to a drug of a different class. The other half underwent HSCT. First, the researchers collected their blood to reinfuse later. Then, they gave patients a combination of drugs to kill most of their immune cells. In this trial, the patients would have regenerated their own immune systems with stem cells in bone marrow that were spared annihilation. But they received the reinfusion of their own stem cell-rich blood to help speed recovery by several days. A year later, the researchers evaluated how far the disease had progressed in each of the patients. According to a zero-to-10 scale of disability that includes measures of strength, coordination, and speech, roughly 25% of those in the drug treatment group showed at least a one-point worsening in their score, compared with just 2% of those in the transplant group. MRI scans also revealed less extensive brain lesions in the transplant group and improvements in a patient survey about quality of life. Five years after treatment, about 15% of people in the transplant group had had a relapse, versus about 85% of the control group.