TGF-β in Marfan syndrome
The ARB Losartan Therapy:
http://www.ncbi.nlm.nih.gov/sites/entre ... m=19635970
Abstract
BACKGROUND: Marfan syndrome (MFS) is caused by mutations in the fibrillin-1 gene and dysregulation of transforming growth factor-beta (TGF-beta). Recent evidence suggests that losartan, an angiotensin II type 1 blocker that blunts TGF-beta activation, may be an effective treatment for MFS. We hypothesized that dysregulation of TGF-beta might be mirrored in circulating TGF-beta concentrations.
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Exogenous IGFs:
TGF-β Inhibits Muscle Differentiation by Blocking Autocrine Signaling Pathways
Initiated by IGF-II
Samantha Gardner, Damir Alzhanov, Paul Knollman, David Kuninger and Peter Rotwein
http://mend.endojournals.org/content/25/1/128.abstract
http://mend.endojournals.org/content/25/1/128.full
TGF-β disrupts an IGF-II-stimulated autocrine amplification cascade
that is necessary for muscle differentiation in vitro.
Because this inhibitory pathway can be overcome by exogenous IGFs,
our observations point toward potential strategies to counteract
disorders that reduce muscle mass and strength.
My interpretation:
Dr. Peter Rotwein took muscle cells, put them in a Marfans-Like environment
(Excess TGF-β), Observed the effects of Marfans (even though he didn�t call it that),
and then overcame the Marfans* (Excess TGF-β) with exogenous IGFs.
*My words and my interpretation on Dr. Peter Rotwein�s in vitro work with TGF-β and overcoming it with exogenous IGFs.
Exogenous IGFs Therapy? My Study:
How did I deliver exogenous IGFs? One (1) mg Somatotropin (rHGH) SQ BD.
I have been unable to find any reported usage of Somatotropin (rHGH) in an MFS patient for either overcoming the TGF-β problem or because of an actual HGH deficiency.
About me:
1982: Age 24, Composite Aortic-Valve/Graft; yes it will be 30, this month.
1989: Aortic Dissection, Proximal Descending-Aorta to the Bifurcation repaired with a short graft of the Proximal Descending-Aorta.
1994: Aortic Graft from the 89-Graft to the Bifurcation.
Returned to work full-time as a Land Surveyor/Civil Engineer.
2008: Hit by a car that ran a red-light, 10-days latter rear ended, when I stopped for a pedestrian at a crosswalk. Diagnosed with a Traumatic Brain Injury, Cranial Nerve Palsy, Diplopia, Strabismus Surgery . . .
Spent 3-years Totally Sedentary.
October 2011: Started Somatotropin (rHGH), 4-months later ran into the 60th percentile on a Stress Echocardiogram.
Early 2012: I stopped the rHGH, for testing; to see if I could have the rHGH covered by Insurance, back on the couch (sedentary) for 6-months.
September 2012: Restarted rHGH; decided I had more money than time.
Today: Feeling and Functioning better than I have in 4-years.
Now, I am still plenty tore-up from the auto accidents, multiple surgeries and underling Marfans. I am still going for vision therapy once a week to work on some residual Diplopia and to PT . . . however; I have made a lot of progress and give a great deal of credit (as do several of my doctors) to the rHGH.
By going public I hope to generate some interest in Dr. Peter Rotwein�s work and maybe that of others, if it exists. I have found no reports of anyone even thinking of using rHGH to treat Marfans in the US. I am spending $80 per day for this one medication; I obviously think it is worth the money.
I was wondering if anyone in this forum has any thoughts on my �study,� or a contact with someone in the scientific community who might have an interest.