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Showing posts from May, 2017

Modulating Neuronal Chloride via WNK

Today�s post is a little complicated, but should be relevant to parents already using bumetanide to reduce the severity of autism.

Tuning neurons via Cl-sensitive WNK
The science behind today�s post only started to evolve twenty years ago when it became understood how chloride enters and exits the neurons in your brain. Nonetheless there is now a vast amount of research and there are parts that have not yet been covered in this blog.

A moving target The first thing to realize is that trying to reduce the elevated level of chloride found in much autism is very much an ongoing battle. Chloride is flowing in too fast via NKCC1 and exiting too slowing via KCC2. If you want to reduce the entry via NKCC1, or increase the exit via KCC2, either of these two strategies should lower the equilibrium level of chloride.Most strategies in this blog target NKCC1, but in another disease (neuropathic pain) the target has been KCC2. Whichever you target, the risk is that the body�s feedback loops come into …

Suramin, the Purinome and Autism

Purinergic signaling is one way cells communicate with each other. It is still an emerging area of science and medicine.

The home of Cell Danger Response and Anti-Purinergic Therapy

Purinergic signaling is an important regulatory mechanism in a wide range of inflammatory diseases. Shifting the balance between purinergic P1 and P2 signaling is an emerging therapeutic concept that aims to dampen inflammation and promote healing. This has some similarity with shifting the balance between th1, th2 and th17 in the immune response. Purinergic signaling plays a role in the nervous system, the immune system and the endocrine system, all implicated in autism. It is one way that microglia in the brain can be activated, which is a common feature of autism.
Robert Naviaux

Robert Naviaux, an autism researcher, believes that
the purinergic signaling complex of a cell, sometimes known as the purinome, lies behind some types of autism. He is researching the use of an old anti-parasite drug called Suramin t…

Boosting Bumetanide with an OAT3 Inhibitor?

Today�s post was prompted by our reader Ling, who highlighted research suggesting another way to improve the potency of bumetanide, a drug many readers have found reduces the severity of autism.

Sometime a little extra boost is necessary

There is an ongoing debate in the literature about how poorly bumetanide crosses into the brain and whether the theoretical chloride-lowering benefit can actually take place in humans.Well for many readers of this blog, we know the answer.

Nonetheless there are efforts underway to improve the potency of bumetanide in neurological disorders. There is a prodrug called BUM5 which has been shown to reverse types of seizure that bumetanide could not, due to much greater potency in the brain. The French bumetanide researchers are themselves looking to develop a more potent drug. Ling highlighted a recent paper that suggested using an old drug called Probenecid to increase the concentration of bumetanide in the brain (and plasma) threefold. This is not a new idea,…