A new therapy in MS is apt to be met by enthusiasm by the patients and extreme caution by their physicians (with the exception of a few enthusiasts). It is the purpose of these my reviews to express enough enthusiasm to seek new or forgotten ways og therapy and simultaneously to remain at a certain distance of claimed successes.
Embryogenic stem cells
Big enthusiasm with embryogenic stem cell therapy was expressed by Ukrainian physicians at Kiew [1]. However, reports of „100% effectiveness“ and „only positive effects“ call for suspicion beyond the curiosity it obviously produces. In the webpage of these physicians, it is mentioned that some 80 patients a year since 1993 visit the clinic, half of them from abroad, where they receive injection of a preparation for numerous indications, among them MS. This preparation consists of frozen embryonic tissues, gained in connection with deliberate abortions (already awakening one of the ethical aspects of embryogenic stemm cells, another is related to cloning of human stem cells but that is not carried out in Kiew). No sort of antigenic testing seems carried out or is judged necessary in advance to the injection which is carried out every 4-6 months the first year and about every 1st or 2nd year thereafter.
It is recommended to question these results. It may well be that one future treatment follows this way, but some rate of failure and some adverse effects (e.g. formation of cancer) must be expected. An absence of adverse effects in preliminary reports is not confirmative and usually expresses unfamiliarity with the therapy. It is really the question if any effective therapy exists which is not associated with some adverse effects. For ethical reasons, a therapy with (possibly cloned) embryogenic cells cannot be expected in Western Europe and North America for several years.
Neural cells
It should be no secret that a better
discrimination of
the progenitor cells than is expressed in this review, is
preferrable.
Any suggestions in this direction are wellcomed.
Glial cell
transplantation
In an animal experiment, Learish et al.
[8] found
that myelin repair might be achieved by intraventricular
delivery of myelin-producing
cells. Similarly, Blakemore et al. [9] could demonstrate
that transplanted
glial cells have a far greater ability to colonise areas of
demyelination
than endogenous cells. Nevertheless, using glial cells
experimentally,
Franklin and Blakemore [10] showed that long distance migration
of remyelinating
cells is not a feature of remyelination.
Neural stem cells
Neural stem cells, as primitive cells that are the
"parent"
cells of all the cells in the CNS were discovered only in 1992.
Kallos
et
al. [11] showed it possible to cultivate them in-vitro but
I am not
aware of any publicaions of their use.
Oligocyte precursor
cells
Oligocytes are cells responsible for the myelin
production
and precursor cells exists [12,13], even in the area of injury
where they
should have been (more) active. Using remyelinating
oligodendrocytes (immature,
cycling cells endogenous to adult white matter), Gensert and
Goldman [14]
demonstrated that this population responds to demyelination by
differentiating
into myelinating oligodendrocytes. However, Jefferson
et al. [15]
found that oligodendrocytes induce collapse and loss of motility
in oligodendrocyte
precursor cells, with this effect being lost as oligodendrocytes
undergo
programmed cell death. Simultaneously, others have found that
oligocytes
still present in a region of demyelinization are much less
active than
„fresh“ oligocytes.
Autologous haemopoietic stem cells
It has long been observed that patients with the combination of an autoimmune disease and a severe blood disease (leukemia, aplasia) were cured of both diseases following allogeneic blood marrow transplantation, used against the latter diseased for decades. There is also an overwhelming experimental study material in favour of this therapy for a number of autoimmune diseases, but the number of patients served by this principle is rather limited. Do not forget that this method is much more aggressive than the other techniques in the depletion of all white blood cells, including the lymphocites, before the virtual transplantation, and this fact ecplains the considerable mortality from the method. Using autologous haemopoietic stem cell transplantation for autoimmune diseases in 390 cases [2], 127 of which were dealing with MS, the treatment was associated with an instantaneous mortality of 1.5% and a one year mortality of 9% which were the ‚costs‘ for success in 2/3 of the cases. In consequence of the workshop referred, prospective randomised phase III trials were now considered appropriate.
In five MS-patients of EDDS 6.5 or more, Saiz et al. [3] found dramatic improvements in four and a less spectacular but still positive effect in one patient following autologous hematopoietic stem cell transplantation. The clinical stabilization was associated with a reduction in the T2 lesion load while the T1 brain lesions at least did not deterorate. Openshaw et al. [4] also used this therapy in 5 MS patients but found severe infectious complications in 3, resulting in the death of one patient 22 days and another 19 months later, at the benefit of stability in the disease in the four instant survivors. In a study of the same therapy on 19 patients with severe autoimmune diseases (3 of them with MS) [5], success was reported in 90% (17 patients?) and no mortality registered. In a much larger report of more than 250 children (mostly not MS), Wulffraat et al. [6] concluded that induces a very significant and drug-free remission of the disease,but carries a significantly risk of developing fatal complications. An animal experiment [7] demonstrated a high mortality from this therapy.
In summary, these studies confirms the high-risk nature of haemopoietic stem cell transplantation, calling for an almost vital threat to consider it at all.
In July 2011, it was reported [16]: "A major clinical trial will investigate whether stem cells can be safely used to treat multiple sclerosis … start later this year … very strong pre-clinical evidence … stem cells from the bone marrow of patients"
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