A Case Study Treating Adult Hypoxia with Clemastine - a potential treatment to promote myelin recovery in premature infants
The researchers go on to suggest Clemastine treatment to promote myelin recovery in premature infants. In this case the graphics in the paper relate to mice, not humans, but are really impressive.
This means that what is called Ataxic Cerebral Palsy, which is caused by a lack of oxygen during birth might now have a treatment.
Some children with autism, including some discussed in the comments in this blog, appear to have suffered hypoxia during birth. This caused damage which resulted in symptoms of autism. You would expect that damage to show up on the “right sort of MRI” in the same way as the adult male, below. Some of these children are reported by parents to respond to hyperbaric oxygen, even though it is carried out years after the hypoxia.
Findings in human DPHL case treated with clemastine. Axial FLAIR (fluid attenuated inversion recovery) at 1 (A), 2 (B), 6 (C), and 12 (D) months after injury in a human case of DPHL, showing MRI white matter abnormalities on FLAIR and diffusion weighted images, subtle at 1 month and striking at 2 months, parallel to patient’s worsening clinical course; white matter signal changes showed a periventricular/ deep white matter distribution with involvement of the corpus callosum (particularly splenium), with sparing of U-fibres. The patient was started on clemastine treatment at 2 months. At 6 months, MRI abnormalities in the white matter were partially normalized, showing fuzzy signal changes, unchanged at 12 months follow-up.
What I found interesting was the time delay, it was two months after the hypoxia that the man’s symptoms became really severe, but rather than being game over, the white patches in the month 2 MRI gradually fade away, after clemastine treatment started.
In my posts on autism and myelin, I pointed out that the problem appears to be re-myelination, which is the repair and maintenance of existing myelin. In autism you could consider it as “Friday afternoon myelination”, when the oligodendrocytes are thinking more about the weekend than your axons. In the man in the case study he already had plenty of myelin prior to his hypoxia, but the hypoxia affected his capacity to re-myelinate his axons.
The progressive cognitive decline with profound short-term memory loss, impaired executive function, and paucity of speech, psychomotor retardation, urinary incontinence and gait impairment was reversed. The patient was seen in follow-up 5 months after his hypoxic event. His cognitive function had markedly improved and he was able to return to work. All thanks to OTC clemastine and I think he should thank someone for reading the Multiple Sclerosis research on clemastine.
The researchers then looked in detail at a mouse model of hypoxia and among other things, Myelin Basic Protein (MBP).
suggesting a rescue of MBP expression defects by clemastine during chronic hypoxia
Daily treatment with oral clemastine during hypoxia leads to significant (3-fold) increases in MBP in the cerebellar foliae compared to untreated hypoxic littermates
We found that oral administration of clemastine in murine neonatal hypoxia leads to significant increases in the numbers of differentiating OPCs expressing the markers proteolipid protein (Plp) and myelin associated glycoprotein (Mag) mRNA in corpus callosum and striatum compared to untreated hypoxic littermates
Clemastine promotes myelin protein expression in neonatal hypoxia.(A) MBP protein expression in the (A) forebrain, (C) striatum white matter of postnatal Day 10 (P10) normoxic mice (‘Normoxia’), versus those exposed to neonatal hypoxia (‘Hypoxia’), versus hypoxic littermates treated with clemastine (‘Hypoxia + Clemastine’)
Hypoxia can injure brain white matter tracts, comprised of axons and myelinating oligodendrocytes, leading to cerebral palsy in neonates and delayed post-hypoxic leukoencephalopathy (DPHL) in adults. In these conditions, white matter injury can be followed by myelin regeneration, but myelination often fails and is a significant contributor to fixed demyelinated lesions, with ensuing permanent neurological injury. Non-myelinating oligodendrocyte precursor cells are often found in lesions in plentiful numbers, but fail to mature, suggesting oligodendrocyte precursor cell differentiation arrest as a critical contributor to failed myelination in hypoxia. We report a case of an adult patient who developed the rare condition DPHL and made a nearly complete recovery in the setting of treatment with clemastine, a widely available antihistamine that in preclinical models promotes oligodendrocyte precursor cell differentiation. This suggested possible therapeutic benefit in the more clinically prevalent hypoxic injury of newborns, and we demonstrate in murine neonatal hypoxic injury that clemastine dramatically promotes oligodendrocyte precursor cell differentiation, myelination, and improves functional recovery. We show that its effect in hypoxia is oligodendroglial specific via an effect on the M1 muscarinic receptor on oligodendrocyte precursor cells. We propose clemastine as a potential therapy for hypoxic brain injuries associated with white matter injury and oligodendrocyte precursor cell maturation arrest.
Conclusion
The days of cheap clemastine in North America are probably numbered.
Conclusion
The days of cheap clemastine in North America are probably numbered.
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