Israeli researchers develop medication to treat statin myopathy - study

Statin myopathy is a disease that develops as a side effect of statins which causes paralysis and eventually leads to death.

By JUDY SIEGEL-ITZKOVICH, Jerusalem Post, MARCH 22, 2023

https://www.jpost.com/health-and-wellness/article-735058

Illustrative image of statins. (photo credit: Euractiv)

Researchers at the Ben-Gurion University of the Negev (BGU) and Soroka Medical Center in Beersheba have developed a medication for statin myopathy which causes paralysis and leads to death.

Statins are the most commonly used medication in lowering blood cholesterol and are taken by tens of millions of people in the Western world. They act through inhibition of the enzyme HMG CoA reductase. Almost a fifth of them develop muscle symptoms (“statin myopathy”) including weakness and pain. In about one percent, this myopathy is severe and does not subside months after cessation of statin treatment.

The research team showed that the disease is caused by a mutation in the gene encoding HMG CoA reductase, inhibiting the enzyme’s activity. Trying to cure this severe hereditary disease, they synthesized and purified Methylmevalonolactone – the normal product of HMG CoA reductase that is missing in those patients. Following testing for safety in mice, the team got an exceptional “compassionate use” permit to give the novel medication – never given to humans before – to the most severely affected patient, who was near death - completely immobile and fully dependent on artificial ventilation.

The medication significantly treats a patient

The patient has now been treated with the medication three times a week for more than a year with no side effects. Not only did she stop deteriorating but she has improved dramatically. She can breathe without support for hours at a time, move her arms and legs extensively and even feed her grandchild. Other patients, some of whom are already in the late stages of the disease, are awaiting treatment.

The study, just published in the Proceedings of the [US] National Academy of Sciences (PNAS) under the title "Limb girdle muscular disease caused by HMGCR mutation and statin myopathy treatable with mevalonolactone,” was supported by the Israel Science Foundation.

Soroka Medical Center in Beersheba (credit: DR. AVISHAI TEICHER/WIKIMEDIA COMMONS)

The researchers estimated that there are dozens to hundreds of Israelis affected by this hereditary disease who could benefit from this effective lifesaving treatment. Based on the successful treatment of the hereditary disease, the research team went on to test whether the medication can be effective in the treatment of the non-remitting muscle problems occurring in about one percent of statin users. Indeed, they showed that the medication was extremely effective in a mouse model system mimicking human statin myopathy.

This is the first study to link muscle pain and weakness to statin use. The whole study, from the human genetics and biochemistry studies to the generation and purification of the medication, to the human and mouse trials – was done as part of the doctoral thesis of Dr. Yuval Yogev, guided by Prof. Ohad Birk, head of BGU’s Kahn Laboratory of Human Genetics, director of the clinical genetics institute at Soroka University Medical Center and a member of the National Institute for Biotechnology.

Based on the findings, the research team is now seeking financial support and/or collaboration with the pharmaceutical industry to push forward standardized production and licensing of the medication to save the lives of many individuals worldwide suffering from this hereditary disorder, as well as enable treatment of tens of thousands of statin-myopathy patients. It should be noted that the procedures of the US Food and Drug Administration (FDA) are more lenient in licensing medications for rare diseases, so rapid progress in the procedure is expected.