Older people have a lot of metabolic waste in their cerebrospinal fluid, of which the amyloid-β associated with Alzheimer's disease is probably of greatest interest at the present time. It is an interesting question as to why this increase over time occurs, particularly considering the point that the presence of amyloid-β and other molecules is dynamic, a constant process of creation and destruction. A number of groups, such as Leucadia Therapeutics, make the case for failure of mechanical systems of drainage by which cerebrospinal fluid leaves the brain. Without that drainage to act as a sink for metabolic waste, the waste accumulates.

EnClear Therapies is a company pursuing a path analogous to that of Leucadia Therapeutics, but instead of restoring drainage they seek to filter cerebrospinal fluid. Increasingly sophisticated filtration of blood for various purposes is fairly common, albeit expensive. The challenge with cerebrospinal fluid is that it is locked away inside the spine and skull. If a suitable mechanical approach could be assembled to safely and reliably access and filter cerebrospinal fluid on a regular basis, which sounds like a tough job, then there are all sorts of things that might be built upon that foundation.

While the company is not initially focused on removal of amyloid-β, that is a possibility for the future, given success. Overall, I'd say that this is a most interesting approach: a worse strategy than restoration of drainage in the sense that each new target requires a development program to build a suitable filter to fit into the machinery, but on the other hand a better strategy for some conditions as it might be possible to clear more of a given target molecule.

EnClear Therapies was conceived with the purpose of developing novel device-based therapies to treat patients with neurodegenerative disease. Toxic proteins are generated in ALS and FTD patients with C9orf72 mutations. These proteins travel through the brain and spinal fluids and are taken up by neurons of the motor system that are very sensitive to their toxicity which leads to degeneration of these neurons leading to paralysis. EnClear has developed a technology which clears these toxic proteins from the brain and spinal fluids of C9orf72 ALS and FTD patients. We are now developing this technology into a device that will recirculate the brain and spinal fluids while the toxic proteins are rendered harmless. With this technology Enclear aims to stop or significantly slow down the neuronal degeneration in ALS and FTD patients with C9orf72 mutations. This technology can potentially be used for other forms of ALS and FTD in which toxic prion like proteins propagate through the brain and spinal fluids. Similar to ALS, Progressive Supranuclear Palsy (PSP) is hallmarked by the buildup of toxic proteins (in this case tau) in the brain. As with ALS, the toxic proteins travel through the brain and spinal fluids and are taken up by neurons that are very sensitive to their toxicity which leads to degeneration of these neurons leading to paralysis. EnClear Therapies aims to halt the progression of PSP by rendering the tau harmless through the same mechanism used for ALS.

Link: https://www.encleartherapies.com