Effect of Pioglitazone Administered to Patients With Adrenomyeloneuropathy
Status:
Completed
Trial end date:
2019-07-01
Target enrollment:
Participant gender:
Summary
X-linked adrenoleukodystrophy is a rare, demyelinating and neurodegenerative disorder, due to
loss of function of a fatty acid transporter, the peroxisomal ABCD1 protein. Its more
frequent phenotype, the adrenomyeloneuropathy in adults, is characterized by axonal
degeneration in spinal cord, spastic paraparesis and a disabling peripheral neuropathy.
Actually, there is no efficient treatment for the disease. The work of the researchers in the
last twelve years dissecting the physiopathological basis of the disorder has uncovered an
involvement of the early oxidative stress in the neurodegenerative cascade and mitocondrial
depletion. In a preclinical trial they have observed that pioglitazone, a PPARγ/PGC-1α axis
metabolic activator with immunomodulatory, anti-inflammatory and antioxidant response
regulator properties, efficiently reverse the clinical symptoms and the axonal degeneration
in the mouse model for the disease and normalize stress and mitochondrial depletion
biomarkers.
The researchers will test the effectiveness of the drug in terms of motor function and
correction of oxidative damage markers in proteins and DNA and inflammation markers in an
open trial. Fifteen-twenty patients will be included and clinically explored and assessed in
the HU of Bellvitge and the HU of Donostia using clinical scales for spasticity, evoked
potentials, electroneurinograms and cranial RMN. The information will be collected in a data
base that will be of great value to improve the present attention and the future follow-up of
the patients and to facilitate their inclusion in therapeutic randomized, double blind,
against placebo, multicentric and international clinical trials.
Phase:
Phase 2
Details
Lead Sponsor:
Onofre, Aurora Pujol, M.D.
Collaborators:
ELA España Association Fundacion Hesperia Instituto de Salud Carlos III