Créditos de imagem: wikicommons.

The relationship between stem cells and amyotrophic lateral sclerosis is relatively complex, but an old one. It has been 13 years now since, in July 2005, we started giving cyclophosphamide in high doses and observed that it had a mild effect on the progression of amyotrophic lateral sclerosis, as others had noted before us. More than 50 patients later, we have almost stopped providing this treatment because of low demand, although it is still available. In the mean time a great amount of neurological literature accumulated supporting this approach, rather than that obsessively supported by classical neurology, that ALS is a degenerative rather than an inflammatory disorder. A number of papers have explored various details of the immunology of ALS, such as

Sheehan et al JAMA Neurology 2018:epub 2018 March 5

Gustafson et al PLoS One 2017:12(7)

Beers et al Proc Nat Acad Sci USA 2008, 105(40): 15558-15563

which all deal with regulatory T-cells and slowly conclude that the inflammation in ALS may be related to an excess of these T-cells, or their disregulation. T-regs, as they are known, are well known to be related to cyclophosphamide, it is even in wikipedia. But the controversial nature of the treatment we have supported for so long is due to a deeply held paradigm that must have originated in neurosurgeons. It is the same they used for multiple sclerosis. It has become obvious that this “degenerative” jargon is purely bias, prejudice, stigma. It is a definition that needs to be taken out of the operational medical dictionary.

Cell death cannot be accomodated in the label “degenerative”. It is either apoptotic or inflammatory. In the case of ALS, cell death is not related to apoptosis. So it can only be inflammatory. And the high doses of cyclophosphamide we have used do have an effect, which is temporary, last for many months, and is more impressive in younger people with disease of more recent onset. Which has become clear internationally, that stem cells and amyotrophic lateral sclerosis, as well as other diseases, are much more amenable to treatment in younger people with a young disease. All stem cell treatments have this nature.

Patients never recover neurological function, they only stop to evolve for a while. That meay be the reason why lesser numbers of people come to have the treatment these days. Although we always informed people of the exact nature of the treatment, they kept their own fantasy that a “stem cell” treatment could lead to a “cure”. When it became obviously clear that this is not the case, they went back to a line of thought with the same  construct in their mind as the neurosurgeons, in which a degenerative disease could only be helped by a miraculous embryonic, fetal, neurological cell treatment.

The hematopoietic stem cells you get in the blood after high doses of cyclophosphamide are blood cells, not neural and not embryonic. They are not pluripotent, they have an imune effect, which, so many years later, is well known. Thus, the coupling of stem cells and amyotrophic lateral sclerosis needs to reemerge, but on a diferente paradigma.

Dr Paulo Bittencourt

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