Monday , January 18 2021

When you have no time for pain

In July, Lipsitz started a monthly injection of erenumab-aooe (Aimovig), one of the three new drugs targeted to the pain transmission signal, a calcitonin gene-linked peptide (CGRP) or its receptor. Monoclonal antibodies, such as the drug, act to block CGRP, the chemical involved in migraine.

"I see him as my lifeguard, I hope," she said. She has had more days in the last three weeks than she had done in the past three years.

The treatment did not eliminate all the pain. Lipsit has failed to remove other drugs. But the new therapy has recovered much of what migraines have taken, especially the time with her husband.

Preventing migraine with CGRP antibodies detects a new world, Broner said. "For the first time, we have a drug developed specifically for the mechanism of migraine, which means that we are really targeting the disease itself."

For decades, doctors treated migraine with therapies developed for other illnesses, using blood pressure drugs, antiseptic drugs, antidepressants, and even Onabotulinum toxin (Botox). Lipsitz is all of these, finding some relief, but also reduces effectiveness over time, or side effects and fatigue. The non-steroidal anti-inflammatory drugs she took for breakthrough pain gave her bloody ulceration and kidney damage.

New drugs are unique because they not only prevent migraine, they are also well tolerated.

"This is the key," says David Dodik, a specialist in neurology and headache at the Mayo Clinic in Arizona. "If I give you something to take and it is effective, but you can not tolerate the side effects, you will stop it."

The recent change in the treatment of migraine comes from a change in understanding the causes of migraine, he said. Migraine has previously been considered a blood vessel problem. It was "a really nervous problem," he said.

The credit for understanding the role that CGRP plays in the brain is largely due to Swedish researcher Lars Ewinson, who began his work 30 years ago. Then he could not buy the peptide, so he built it, linking 37 pieces of "lego" like amino acids, he said.

In 1990, Edwinsson and colleague Peter Godsby sought CGRP in migraine patients by taking blood samples from the jugular vein near the release point in the brain rather than in the arm where the levels were diluted. They showed that CGRP is the only neuropeptide released during the headache.

Some of the new antibody drugs – galanthusumab (Emgality), fremanezumab (Ajovy) and epinsezumab, are already in Phase 3 clinical trials and administered as a three-month infusion – targeted CGRP directly while erenumab (Aimovig) with which the protein transmits pain. Blocking the receptor is like putting chewing gum into the lock, Dodik said.

"You can not get the key anymore, you can not open the door," he said.

Since these antibody drugs are proteins, they do not interact with other medicines in the liver or keep the blood vessels, considerations for patients taking other medicines, and one of the limited aspects of tryptans, the class of medicine used to stop migraine is considers the enormous progress they have made since the 1990s.

However, not all people will respond to CGRP-related therapies. And while clinical trials show few side effects, large patient populations have not yet been followed in long distance studies. CGRP is involved in other functions including the heart and skin, and there are reasons to be cautious, said Broner.

"I do not run and prescribe it to everyone," she said. New drugs are also expensive, costing about $ 7,000 a year, and not always covered by insurance. Tina Ansari, who has reduced the frequency of her chronic migraines to 12 months with injections of Botox, added Aimovig to her regime with a program designed to give patients up to 12 doses free of charge while they are pursuing approval for coverage.

"I'm not an experimental person," said Ansari. "But at this point in my life I have been suffering for so long."

After two months of Aimovig, she had a migraine and her daily headaches were less painful, down from "7 to 4."

"I can drive my kids, I live my life, it's a change player," she said.

Her three boys, ages 10, 12 and 14, have just started working together. She hopes to be able to join them someday.

"If I could get to the point where I could run again, that would be amazing," she said.

Neurostimulation that uses electrical stimulation to treat pain also gives patients more opportunities, especially when developing non-invasive devices or less invasive procedures.

The techniques used to carry the "end of the road," said Goadzby, a professor of neurology at King's College London and the University of California at San Francisco. But the unpulmonary transcutaneous stimulation that can prevent and cure attack is a handheld device that patients use at home. Goadsby said that options that do not have "luggage down" are a valuable consideration for those most affected by migraine: women in reproductive years who have additional drug considerations when they are pregnant or breastfeeding.

These devices are also becoming more affordable for initial costs, said Peter Staats, founder of the Department of Hospital Medicine at the Johns Hopkins Anaesthesiology Department, who developed a manual non-invasive nerve stimulator, gammaCore, approved in January for migraine treatment.

"We think it's a digital drug," he said. Doctors write a prescription, and if they are insured, the patient pays the kopeck. They receive a RFID card similar to the cards used to open the hotel doors that activate their device. Patients recharge the card as needed, just like completing the recipe.

"If it does not work, they have not bought anything that will be expensive and will sit on the shelf," he said.

Robert Levy, president of the International Society of Neuroimaging and Neurosurgeon and Researcher, said non-invasive therapies did not work for all patients. He studies a model of minimal invasive nerve stimulation, individualized to where patients experience pain described as "stimulating where the model hurts." Small wires are implanted under the skin of the scalp and connected to a battery similar to a pacemaker. The degree of success for patients has been significantly improved over the stimulation that is directed only at the back of the head, he said.

"It is extremely important to be able to offer patients care and hope," he said.

The complexity of migraine – driven by a combination of genes interacting with the environment – means that no treatment will work for everyone. More drugs are in the pipeline. What is important today is that migraine has a specific treatment that is no longer undergoing a "soft illness," said Gadzby.

Recently, he wrote his first drug recipe for CGRP.

"It is strange to think about something for three decades, then take the pen and carefully print it out," he said. – It's surreal.

If his colleague Edwinsson was not rejected by a professor of neuronatomy as a 20-year-old student, their collaboration with the CGRP could not have happened.

"Well, it's already been discovered," Edwin's professor told him when he wanted to help with the research.

During the next semester, Edwinsson tried the histochemistry section.

With migraine, there was and still has a lot to learn.

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