Targeting CB1 Receptors With Antibodies

A recent press release from the pharmaceutical company Integral Molecular, written by Kate Kadash-Edmondson, has demonstrated the safety of a new therapeutic target for the endocannabinoid system (ECS): monoclonal antibodies for the ECS receptor CB1. Previous attempts at targeting this receptor have been tried before for various other ailments, such as obesity, as reviewed in earlier editions of this newsletter, only to have their products fail due to unforeseen adverse psychiatric side effects. In the case, a typical molecular compound (i.e. old fashion pill) was used to target CB1. Integral Molecular is going about it a new way, via the use of monoclonal antibodies (mAb). See video below for a crash course on mAb therapy.

Photo Source: UnSplash.com

A brief summary of the ECS. The ECS is made up of neurotransmitters ([NTs] anandamide, 2-AG, and various other compounds), receptors (most famous are the CB1 and CB2 receptors) and the various enzymes that are used to produce and degrade ECS NTs. The ECS runs all throughout our body and is responsible for several regulating mechanisms, including homeostasis, pain modulation, appetite, memory, and perception. Targeting the receptors in the ECS can have both effects in the periphery (e.g. modulating pain) and the central nervous system (CNS) (e.g. euphoria). The trick in using the ECS to treat a physical disease in the peripheral nervous system (PNS) is keeping it from crossing the blood-brain barrier, a challenge many therapies face.

Integral Molecular is trying a new approach, one made famous by the push in immuno-oncology therapies. Because it is a mAb, it is too large to cross the blood brain barrier. So it sticks around in the PNS, which makes it a great alternative if you are concerned about neurological or psychiatric side effects. Integral Molecular is targetting the CB1 receptor in the PNS to treat the liver disease nonalcoholic steatohepatitis (NASH) and metabolic disorders. It turns out that the CB1 receptor may be involved in inflammation and ultimately liver injury. With the mAb approach, scientists can antagonize (i.e. block) the CB1 receptors in the liver to prevent further damage.

Photo Source: pixabay.com

Integral Molecular has just received a grant to study their drug in preclinical models. We are not sure what the future holds for this treatment, but hopefully, with its ability to stay within the PNS, its specificity that comes with mAbs, and the sound scientific reasoning to indicate that CB1s do contribute to liver problems, this sort of treatment can be used for many more ECS-related diseases. The video below is a quick guide on the therapeutic applications of mAbs in treating all sorts of diseases. This type of immunotherapy may one day replace the pharmacological model of treatment, leading to fewer side effects and more efficacy.

Video Source: YouTube.com

Sources: IntegralMolecular.com, LinkedIn.com, Labroots.com, Wikipedia.com - Monoclonal Antibodies, Cold Spring Harbor Perspectives in Biology, Journal of Hepatology

Correction: In an earlier publication of this article it was stated that Integral Molecular were in Phase II clinical trials. They are not, instead they are still in the preclinical phase.