Monday 15 March 2021

CRISPR a ray of hope to cure Pain forever…

 



Pain is the most unpleasant type of sensory response received by human brain and is often more or less associated with an under lying condition which tends to inflict some sort of physical damage to body tissues, the very sensation pushes human conscience to develop strategy to protect its damage body parts for enabling proper healing and recovering full working capacity of damaged tissues. But this very sensation has a darker aspect, in certain diseases pain to be endured is too much for any human being and this often leads to decision relating to ending one’s life. Another key issue exists in form of chronic pain where a person consistently feels pain for months or even years despite of recovering from original cause in form of an injury or a disease, according to an estimate ranging from 19-50% of global population experiences chronic pain for a greater part of their life and in response recommended opioids often produce numerous side effects which leads to development of some diseases or may cause conditions of substance abuse. Now this overall situation demands a solution one that can suppress or cure pain in certain medical cases and prolongs life span with a possibility of some cure in near future. In this regard the CRISPR based genome editing is now proving to be a ray of hope at the very end of a dark tunnel.

The pain tunnel

Now the brain experiences sensation of pain upon receiving some sort of stimulus like touching a hot pan, getting some sort of cut and so on, this triggers a series of electrical signal inside human nervous system which convey signals of pain. Inside body the nervous system is made up of a neurons and each neuron has small pore like openings present on its surface called the ion channels. These channels consistently open and close to allow neuro-chemical communication in nervous system and among these channels is the sodium Na v1.7 channel which allows pain signalling with influx of sodium ions inside neurons. Although there are many studies which have suggested that a sodium channel called Na v1.7 could play a central part in chronic pain, but in various cases when people have mutations in the gene coding for this channel, they either experience extreme, constant pain, or can’t feel any pain at all. Scientist have been trying to block these Na v1.7 channels by using certain small-molecule drugs and antibodies, but they often struggled because these therapies also interact with structurally similar sodium channels in the body leading to severe complications, in order to deal with this issue and find a cure for this pain by manipulating ion channels researcher from University of California, San Diego lead by PhD candidate Ana Moreno decided to harness power of modified version of CRISPR/CAS9  molecule which tends to locate gene with precision and modify its function without any off target effects.

Pain signals are transmitted to the brain through neurons similar to these in the spinal cord


CRISPR Ray of Hope:

the team utilized a variant of CAS9 called the dcas9 (de natured CAS9)  in which the molecule perform all standard functions from gene targeting to binding but only the cleavage function is absent, the molecule is then attached with a repressor molecule which prevent expression of that gene, the team encoded this dCAS9 for Na v1.7 gene in order to suppress its expression and reduce pain sensation. Molecule was then injected in to a mice followed by chronic pain stimulus with chemotherapy and results show high tolerance of pain in mice for up to 44 weeks, similar level of tolerance was also observed in mice that previously had issues involving chronic pain. The dCAS9 molecule only binds with certain gene and prevent its expression for a certain time this also prevents permanent changes in DNA and revives the ability to feel pain once the baseline cause of chronic pain has been resolved bringing back life to normal.

Senior neuro-scientist Sulayman Dib-Hajj, at Yale University describe that although this is still far from human trials but it is a great  and highly successful start with nearly 44 week relief this can revolutionize the entire treatment procedures for various painful diseases.

Conclusion:

Cure of pain for a certain time frame can provide various patients a temporary necessary relief from serious pain experienced during treatment procedure like for cancer treatments and so on. Also it can provide number of options for athletes to soldiers as for how they really want to deal with their injury and what level of compromise they would be ready to make with their profession for healing a certain injury. This research also provide a possible hope for also recreating pain sensation by certain degree of reengineering in case of certain disease related to pain insensitivity which often lead to serious life threatening injury and loss of organs in patients having such conditions.

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