Designing a combination therapy for acute ischaemia

If one were to design a combination therapy for neuroprotection and neurosupport following a major ischemic stroke, they might decide to do something like this in continuous IV delivery form:

To limit reperfusion injury, and limit apoptosis cascades, and provide immediate support

L-Glutathione, Vitamin C, N-Acetyl Cysteine, and Sodium Butyrate to help limit reperfusion injury, and limit the infarction injury areas to only the immediately affected neurovascular system, including reducing glutamate-related toxicity.

Many of these substances have more than one purpose in this mix. The L-Glutathione and N-Acetyl Cysteine operate as ROS-antioxidants and prevent other forms of cellular damage. The Vitamin C takes some of the load off the vitamin C scavenger pathways which exhaust L-Glutathione stocks to recycle Vitamin C after use, ensuring that L-Glutathione can focus on its other role.

A DHA/triglyceride emulsion should be included in this mix delivered for the first few hours, then later should be replaced by DHA/EPA (see below).

Neurosupport, neurogenesis, repair and remodelling

To the above neurovascular protectants, we add: L-Serine, phosphatidylserine, and citicoline to provide the necessary building blocks for neurogenesis, repair and remodeling.

(Phosphatidylserine might be left out of this mix - testing is required to determine if it’s more helpful than L-Serine alone, or if it interferes with healing. If in doubt stick to just L-Serine. Depending on the kind of injury, phosphatidylserine might help more in some cases than others, as it’s expressed at the damaged ends of nerves to target them for repair).

Thromboyltic agents (anti-clotting agents)

rPTA therapy is currently the gold standard for breaking down clots, and should probably be administered once the above listed substances are in the blood stream in sufficient concentration (or co-administered). rPTA can tail off without stopping delivery of the other listed substances.

Matrix metalloprotease inhibitors (e.g. doxycycline, tetracycline, minocycline)

These should be used to prevent large scale remodeling of the area during repair (and potentially also protect the area from certain classes of bacteria - and possibly also further clots/bleeds by inhibiting porphyrin/gingipain-producing bacteria).

Capillary/Endothelial relaxation

Nicotinic acid (vitamin B3) to trigger flushing reaction and relax the endothelium, particularly in small capillaries.

Nutritional support

DHA/EPA as raw building blocks (in addition to normal TPN nutrition for proteins). This is after the first day or so of DHA + triglycerides.

B-vitamins, and other protein sources are pretty obvious. But omega 3’s are essential for some of the necessary repair work. They should be fresh, and have been kept chilled to avoid rancidity, ideally only being warmed to body temperature during infusion, and possibly kept in an anoxic environment, with a short wavelength-light blocking bag.

Delivery phases

• This would be delivered in phases - first the anti-ROS group, neurogenesis group. MMPI antibiotics + rPTA after a few minutes (rPTA therapy ramping off over time according to the existing protocols for use). DHA/trigly. replaced with DHA/EPA after about a day or two. Not sure when to start introducing the B-vitamins, particularly B3.

Contraindications

Extreme care would be needed before attempting this on a patient with an intracranial haemmorhage or bleed, rather than a clot. For patients already on blood thinners who have a seemingly paradoxical clot, consider increasing the dose of matrix-metalloprotein inhibitor antibiotics and reducing the blood thinners dosage gently as DHA/EPA, NAC and other treatments in this list all have a blood-thinning/anti-clotting effect.

Notes

The difficulty with such a therapy is not only getting anyone outside of researchers in Barcelona to try this, but the fact that it works best within the first three hours. I expect something like the above mix to become standard medical practice in about 30 years, assuming we don’t come up with better mechanisms involving nanotech or RNA therapy.