Encouraging Results with Stem Cell Treatment of MS

This needs to be replicated before any conclusions can be drawn, but it
is encouraging.  21 patients with relapsing-remitting href="http://health.nytimes.com/health/guides/disease/multiple-sclerosis/overview.html?scp=1-spot&sq=multiple%20sclerosis&st=cse">multiple
sclerosis, in whom conventional treatment failed, were given a stem
cell treatment.  17 patients improved; 16 had no relapse at all;
none got worse.  They were studied over a period of two to four
years.  The study was published in The Lancet Neurology, (
Early Online Publication, 30 January 2009) $ for full access:

href="http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2809%2970017-1/fulltext">

href="http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2809%2970017-1/fulltext">Autologous
non-myeloablative haemopoietic stem cell transplantation in
relapsing-remitting multiple sclerosis: a phase I/II study

doi:10.1016/S1474-4422(09)70017-1

Background

Autologous non-myeloablative haemopoietic stem cell transplantation is
a method to deliver intense immune suppression. We evaluated the safety
and clinical outcome of autologous non-myeloablative haemopoietic stem
cell transplantation in patients with relapsing-remitting multiple
sclerosis (MS) who had not responded to treatment with interferon beta.

Methods

Eligible patients had relapsing-remitting MS, attended Northwestern
Memorial Hospital, and despite treatment with interferon beta had had
two corticosteroid-treated relapses within the previous 12 months, or
one relapse and gadolinium-enhancing lesions seen on MRI and separate
from the relapse. Peripheral blood haemopoietic stem cells were
mobilised with 2 g per m2 cyclophosphamide and 10 μg per kg per day
filgrastim. The conditioning regimen for the haemopoietic stem cells
was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg
per kg rabbit antithymocyte globulin. Primary outcomes were
progression-free survival and reversal of neurological disability at 3
years post-transplantation. We also sought to investigate the safety
and tolerability of autologous non-myeloablative haemopoietic stem cell
transplantation.

Findings

Between January, 2003, and February, 2005, 21 patients were treated.
Engraftment of white blood cells and platelets was on median day 9
(range day 8--11) and patients were discharged from hospital on mean day
11 (range day 8--13). One patient had diarrhoea due to Clostridium
difficile and two patients had dermatomal zoster. Two of the 17
patients receiving alemtuzumab developed late immune thrombocytopenic
purpura that remitted with standard therapy. 17 of 21 patients (81%)
improved by at least 1 point on the Kurtzke expanded disability status
scale (EDSS), and five patients (24%) relapsed but achieved remission
after further immunosuppression. After a mean of 37 months (range 24--48
months), all patients were free from progression (no deterioration in
EDSS score), and 16 were free of relapses. Significant improvements
were noted in neurological disability, as determined by EDSS score
(p<0·0001), neurological rating scale score
(p=0·0001), paced auditory serial addition test
(p=0·014), 25-foot walk (p<0·0001), and quality of
life, as measured with the short form-36 (SF-36) questionnaire
(p<0·0001).

Interpretation

Non-myeloablative autologous haemopoietic stem cell transplantation in
patients with relapsing-remitting MS reverses neurological deficits,
but these results need to be confirmed in a randomised trial.

Funding

Division of Immunotherapy, Northwestern University.

There are two articles already in the popular press: one in href="http://www.bloomberg.com/apps/news?pid=20601124&sid=akHXxf3bS3TY&refer=home">Bloomberg,
of all places, and one in href="http://www.newscientist.com/article/dn16509-multiple-sclerosis-reversed-with-stem-cell-therapy.html">New
Scientist. 



Note that the patients were treated with their own (adult) stem cells,
so this is not directly pertinent to the href="http://scienceblogs.com/insolence/2008/10/stem_cell_controversy_in_michigan.php">controversy
over embryonic stem cells.  It is indirectly pertinent,
however, in a way.  One argument against the use of embryonic stem
cells is that it is not permissible to use embryonic cells, when adult
cells could be used instead.  This is a bogus argument, but we can
expect that it will be aired again.



Now, as for the study itself: is was not randomized, it was not a
double (or even single) blind study, and it was small.  But the
results are impressive, especially since the patients were all people
who had not responded to treatment with steroids and/or interferon.



Note, however, that the treatment is hardly benign.  After the
cells are harvested from the patients, the patients undergo
obliteration of their immune systems.  From the New Scientist
article:

They removed stem cells from the patients' bone marrow, and
then used chemicals to destroy all existing immune cells in the body,
before re-injecting the stem cells. These then developed into
naïve immune cells that do not see myelin as alien, and hence do
not attack it.

Presumably, this is why some of the patients had complications: two
developed herpes zoster; one developed Clostridium difficile
colitis.  In addition, two patients developed href="http://en.wikipedia.org/wiki/Immune_thrombocytopenic_purpura">ITP. 




The Bloomberg article mentions that a second study is
underway.  This one will include 55 patients.  Presumably, it
will be many years before treatment based upon this concept will be
available to the general public.