What you see is what you get,
not what you see is what he took.
Today’s post is another very short one.
You may have
seen that Maria Sharapova, the tennis player has
got into trouble for taking a Latvian drug called Meldonium/Mildronate for the
last decade.
Like many people, I did a quick check on this drug to see what it does and if you could innocently not know that it is performance enhancing. Well it does lots of performance enhancing things like increasing blood flow and increasing your capacity to exercise.
What drew my attention was its effect on mitochondria,
cognition and even as a potential Alzheimer’s Therapy.
I should point out that Bumetanide, the most
effective Autism therapy my son uses, is also a banned substance under the
World Doping Agency rules. Bumetanide
and other diuretics are used as masking agents by athletes taking performance enhancing
drugs.
Mildronate
Mildronate
is a Latvian drug, widely prescribed across the former Soviet Union.
For people with autism who respond to carnitine therapy,
or with a diagnosed mitochondrial disorder it looks very interesting. There really are no approved treatments that
reverse such disorders, just to stop them getting worse.
Mildronate also shows some promise for both Parkinson’s
and Alzheimer’s disease in animal models.
Mildronate improves cognition and reduces amyloid-β pathology in transgenic Alzheimer's disease mice
Mildronate, a
carnitine congener drug,
previously has been shown to provide neuroprotection in an
azidothymidine-induced mouse model of neurotoxicity and in a Parkinson's
disease rat model. The aim of this study was to investigate the effects of
mildronate treatment on cognition and pathology in Alzheimer's disease (AD)
model mice (APP(SweDI)). Mildronate was administered i.p. daily at 50 or 100
mg/kg for 28 days. At the end of treatment, the animals were behaviorally and
cognitively tested, and brains were assessed for AD-related pathology,
inflammation, synaptic markers, and acetylcholinesterase (AChE). The data show
that mildronate treatment significantly improved animal performance in water
maze and social recognition tests, lowered amyloid-β deposition in the
hippocampus, increased expression of the microglia marker Iba-1, and decreased
AChE staining, although it did not alter expression of proteins involved in
synaptic plasticity (GAP-43, synaptophysin, and GAD67). Taken together, these findings indicate
mildronate's ability to improve cognition and reduce amyloid-β pathology in a
mouse model of AD and its possible therapeutic utility as a disease-modifying
drug in AD patients.
This review for the first
time summarizes the data obtained in the neuropharmacological studies of
mildronate, a drug previously known as a cardioprotective agent. In different
animal models of neurotoxicity and neurodegenerative diseases, we demonstrated
its neuroprotecting activity. By the use of immunohistochemical methods and
Western blot analysis, as well as some selected behavioral tests, the new
mechanisms of mildronate have been demonstrated: a regulatory effect on mitochondrial processes and on
the expression of nerve cell proteins, which are involved in cell survival,
functioning, and inflammation processes. Particular attention is paid to
the capability of
mildronate to stimulate learning and memory and to the expression of neuronal
proteins involved in synaptic plasticity and adult neurogenesis. These
properties can be useful in neurological practice to protect and treat
neurological disorders, particularly those associated with neurodegeneration
and a decline in cognitive functions.
The obtained data give a new insight into the influence of mildronate on the central nervous system. This drug shows beneficial effects in the regulation of cell processes necessary for cell integrity and survival, particularly by targeting mitochondria and by stabilizing the expression of proteins involved in neuroinflammation and neuroregeneration. These properties can be useful in neurological practice to protect and treat neurological disorders, such as Parkinson’s disease, diabetic neuropathies, and ischemic stroke. Moreover, because mildronate improves learning and memory, one may suggest mildronate as a multitargeted neuroprotective/ neurorestorative drug with its therapeutic utility as a memory enhancer in cognitive impairment conditions, such as neurodegenerative diseases, schizophrenia, and other pathologies associated with a decline in awareness.
The obtained data give a new insight into the influence of mildronate on the central nervous system. This drug shows beneficial effects in the regulation of cell processes necessary for cell integrity and survival, particularly by targeting mitochondria and by stabilizing the expression of proteins involved in neuroinflammation and neuroregeneration. These properties can be useful in neurological practice to protect and treat neurological disorders, such as Parkinson’s disease, diabetic neuropathies, and ischemic stroke. Moreover, because mildronate improves learning and memory, one may suggest mildronate as a multitargeted neuroprotective/ neurorestorative drug with its therapeutic utility as a memory enhancer in cognitive impairment conditions, such as neurodegenerative diseases, schizophrenia, and other pathologies associated with a decline in awareness.
Mildronate, a representative of the aza-butyrobetaine class
of drugs with proven cardioprotective efficacy, was recently found to prevent dysfunction of complex I
in rat liver mitochondria. The present study demonstrates that
mildronate also acts as a neuroprotective agent. In a mouse model of
azidothymidine (anti-HIV drug) neurotoxicity, mildronate reduced the azidothymidine-induced
alterations in mouse brain tissue: it normalized the increase in caspase-3,
cellular apoptosis susceptibility protein (CAS) and iNOS expression assessed by
quantitative and semi-quantitative analysis. Mildronate also normalized the
changes in cytochrome c oxidase (COX) expression, reduced the expression of
glial fibrillary acidic protein (GFAP) and cellular infiltration. The present
results show that the neuroprotective action of mildronate results at least
partially from anti-neurodegenerative (anti-apoptotic) and anti-inflammatory
mechanisms. It might be suggested that the molecular conformation of mildronate
can facilitate its easy binding to mitochondria, and regulate the expression of
different signal molecules, hence maintaining cellular signaling and survival.
Conclusion
If any of the Russian
readers of this blog have trialed Mildronate in their child with autism secondary
to mitochondrial disease (AMD), please let us know the result.
Perhaps Dr Kelley should
try mildronate, it clearly falls into his area of interest.