The thought is it takes not only growth factors and neurotrophins, but ALSO an elevation in cAMP at the same time in order for CNS regeneration to result.
I propose to go one step farther (based on prior research of mine). If you can also block PKC activity, inhibit Nogo-A/NgR (which is a protein that has been found to impair regeneration in the CNS after injury), and also enhance GAP-43 at the same time as increasing neurotrophins and elevating cAMP, what have you got then? The possibility or even probability of activating axonal regeneration in the adult CNS in vivo?? I'd say YES!
Just as a side note, desipramine does all of the above.
Today I find another reference regarding axonal regeneration which also brings my and Wesley's theories together. How uncanny! Here is a publication regarding axonal regeneration and polyamines. Which again, desipramine is the drug of choice that does this, also.
All I can say right now is that there are (finally) some people in MS research studying what I have found in connection to desipramine. Keep your fingers crossed.
Implications for regeneration
The recent explosion in our understanding of the nature
of the myelin-associated inhibitors and how they interact
with neurons has vastly increased the number of potential
therapeutic targets. The finding that a single neuronal
receptor binds with comparable affinities and mediates
the effects of all three of the major myelin-associated
inhibitors was not only a surprise but also suggested
redundancy of activity amongst these inhibitors. In other
words, the effects of these myelin-associated inhibitors
are not cumulative but are independent of one another,
and the relative contribution of each to the block of axonal
extension will depend on their relative level of expression
at the periaxonal surface. This suggests that it may be
possible to block a single target and thereby abrogate the
inhibition of axonal regrowth by myelin and hence,
induce regeneration after injury. However, if an agent
to block the binding of inhibitors to the NgR is to be designed,
extensive knowledge of the relevant binding site(s) must be gained.
The redundancy of all three inhibitors is consistent with
findings that the effects of all myelin-associated inhibitors
can be overcome simultaneously by altering certain inte-
gral, intracellular signaling molecules. One such molecule
is the small GTPase, Rho. Blocking Rho signaling can
promote axonal regeneration both in the presence of
MAG and myelin in vitro and following CNS injury
in vivo . It has been suggested that it is the interaction
of the inhibitory signaling complex with p75NTRthat
modulates Rho’s activity [29,30]. Hence, therapeutic
approaches that target the Rho signaling pathway may be
one method by which a simultaneous block of all the
major myelin-associated inhibitors could be achieved.
Two recent studies by McKerracher’s group [32,33]
indicate that this may indeed be the case. Inactivation
of Rho or its downstream effector Rho-associated kinase
(ROK) can induce improved axonal growth of primary
neurons on inhibitory substrates in vitro [32,33], and
following CNS injury, can permit increased regeneration
and functional recovery in vivo .
Another potential target for improving axonal regenera-
tion is the intracellular second messenger, cAMP. It has
previously been shown that increasing the levels of cAMP
can mediate a reversal of the effects of MAG on both
axonal extension  and growth cone turning 
in vitro. In addition, it has long been recognized that
inflicting a pre-conditioning peripheral lesion on DRG
neurons results in the regeneration of the CNS branch of
the same neuron when it is subsequently lesioned [36–38].
Recently, it has been suggested that CNS regeneration as
a consequence of peripheral lesioning is also mediated by
an increase in intracellular cAMP levels [39,40]. In
support of this hypothesis, studies show that microinjec-
tion of a cAMP analogue in the absence of a conditioning
lesion can mimic the regenerative effects of such a lesion.
Elevation of cAMP in vivo can also improve subsequent
axonal growth of neurons when they are cultured on
inhibitory substrates in vitro. Furthermore, we have
shown that one of the downstream components of this
signaling pathway is a synthesis of polyamines that results
from an upregulation of Arginase I, which is a key enzyme
in their synthesis . Overexpression of Arginase I or
exogenous application of polyamines can mediate im-
proved axonal regeneration on myelin substrates, suggest-
ing a mechanism by which myelin-associated inhibitors
can be overcome. These findings can be explained by a
model in which the binding of a single receptor by
multiple ligands (i.e. the myelin inhibitors) initiates the
activity of the same intracellular signaling pathway(s);
thus, mechanisms that overcome the action of one inhi-
bitor may be able to overcome the inhibitory actions of all
three of the major myelin associated inhibitors. These
experiments reaffirm the idea that actions mediated by
NgR are the major inhibitory components of myelin-
There has been a recent explosion in the identification of
specific myelin-associated inhibitors, and the receptor
that mediates their actions has also been unveiled. This
represents a major leap forward in our understanding of
the contribution of the damaged myelin sheath to the
block of axonal regeneration, which occurs following
injury to the adult CNS. In addition, these findings
provide a starting point for new avenues of research,
which will result in the elucidation of the downstream
signaling components of this inhibitory complex.
Furthermore, recent evidence suggests that blockage of
the inhibitory signaling can be achieved via an elevation of
the intracellular second messenger, cAMP. This elevation
of cAMP has been shown to induce transcriptional activa-
tion and a subsequent increase in the synthesis of poly-
amines, which may play a role in this block of inhibition.
Taken together, the body of work presented in the past
year reveals a single theme: blocking a common receptor
prevents a common signaling pathway (Figure 2). This in
turn, allows for the abrogation of the effects of all of the
myelin-associated inhibitors. If applied before formation of
the glial scar, blocking th ereceptor could result in improved
regeneration and functional recovery after CNS injury.
Schematic representation of the major myelin-associated inhibitors and the proposed receptor complex that mediates their signaling. All three inhibitory molecules (Nogo-66, MAG and OMgp) bind to NgR. This in turn associates with p75NTR to transduce a signal that results in the activation of the small GTPase Rho as well as other, as yet unidentified, signaling cascades leading to the inhibition of axonal growth following injury. The intracellular upregulation of the small second messenger molecule cAMP leads to the activation of protein kinase A. This signaling cascade initiates the induction of gene transcription, including the synthesis of Arginase I, the rate limiting enzyme in the polyamine synthesis pathway. Upregulation of polyamines in turn initiates a block of the growth inhibition induced by the myelin-associated inhibitors. The small peptide NEP1-40 can bind to NgR and inhibit binding of the myelin inhibitor Nogo-66 but not of MAG.
Current Opinion in Neurobiology 2003, 13:133–139 ....