onapristone/progesterone

[Guest guest]

I was struck by a few key issues in these experiments with

Onapristone//Progesterone:

1. Female CMT rats, although clinically indistinguishable from male CMT

rats, were

excluded to avoid any interference with changing endogenous progesterone

levels.

2. Onapristone, a selective progesterone receptor antagonist was

originally developed to treat primary breast cancer.

3. Although treated at a young age, we observed no obvious developmental

abnormalities in CMT rats and wild-type controls as a result of

progesterone or onapristone treatment.

4. CMT rats treated with onapristone maintained a significantly larger

number of axons.

5. Although onapristone did not 'rescue' the disease, it improved motor

performance.

6. Progesterone enhanced disease progression.

7. Data shows that onapristone improves the CMT phenotype in

Pmp22-transgenic rats by slowing disease progression.

8. There are no obvious clinical differences between male and female

human CMT-1A patients, but case reports document a connection between

pregnancy (with up to tenfold increase in progesterone plasma level) and

the worsening of clinical symptoms of CMT-1A.

9. Future studies with onapristone and more recently developed

antiprogestins (lacking the side effects reported for onapristone in

humans will include female CMT rats as a separate treatment arm, and

will extend into long-term observations (greater than 1 year).