Indazole chloride: A Chemical with Potential to Cure Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory disease in which myelin sheath, the insulating cover of nerve cells of central nervous system are damaged. It is an autoimmune disease affecting about 2.3 million people globally. Generally more women than men are affected.

MS is an unpredictable disease, disrupting the ability of parts of the nervous system to communicate, resulting in a wide range of signs and symptoms. It is triggered by the attack of myelin sheath by the immune system, causing the disruption of nerve impulses. Thus patient’s vision, sensation and mobility gets impaired. Permanent paralysis may also result in extreme conditions.

However the available therapies, which prevent the onset of this permanent disability, are only partially effective.

Recently a biomedical research team, from the University of California, Riverside, reports the identification of a chemical: indazole chloride (Ind-Cl), which stops the symptoms and reverses ongoing motor deficit due to MS in transgenic mice. This specific drug can re-myelinate damaged axons not only in MS patients but also in traumatic brain and spinal cord injury.

Ind-Cl stimulates ERβ, an oestrogen receptor. It is well known that high oestrogen levels have neuro-protective benefits, which improve MS symptoms. Thus pregnant women get almost complete relief from MS symptoms in their third trimesters, but following the child birth, MS symptoms return as the oestrogen levels plummet. Therefore oestrogen could be the key therapeutic molecule for MS, though high levels of oestrogen are linked to breast and uterine cancers and feminizing effects in men. But this unique ligand turns on ERβ without showing any negative effects of excessive oestrogen. It also inhibits selective inflammation of the central nervous system permanently. The researchers conducted electrophysiology tests to ensure the transmission of impulses by the re-myelinated axons.

To establish that remyelination, was due to the drug rather than immune response the researchers administered Ind-Cl in mice whose oligo-dendrocytes (cells responsible for remyelinating axons and myelin) were selectively low. They observed more efficient remyelination in such cases, thereby demonstrating that Ind-Cl works in two ways: indirectly through immune system by reducing brain and spinal cord inflammation, and directly by remyelinating axons. This makes Ind-Cl an extremely promising drug.

Moreover this compound can also work after the disease onset. An MS patient typically first visits the doctor when the axons have been severely affected and he or she has noticed some motor deficits, like loss of balance, inability to pick up an object, vision impairment. Ind-Cl can be administered at this point because it would not only prevent further damage but also help to reverse the symptoms. The researchers think that Ind-Cl can be developed for oral administration also, which is definitely an added advantage.

Several other Ind-Cl analogues could work even better at alleviating MS symptoms. The group has already identified four other analogues that would soon be tested on MS mice. They expect to select some of them for clinical trial also in near future.

Multiple sclerosis (MS) is an inflammatory disease in which myelin sheath, the insulating cover of nerve cells of central nervous system are damaged. It is an autoimmune disease affecting about 2.3 million people globally. Generally more women than men are affected.

MS is an unpredictable disease, disrupting the ability of parts of the nervous system to communicate, resulting in a wide range of signs and symptoms. It is triggered by the attack of myelin sheath by the immune system, causing the disruption of nerve impulses. Thus patient’s vision, sensation and mobility gets impaired. Permanent paralysis may also result in extreme conditions.

However the available therapies, which prevent the onset of this permanent disability, are only partially effective.

Recently a biomedical research team, from the University of California, Riverside, reports the identification of a chemical: indazole chloride (Ind-Cl), which stops the symptoms and reverses ongoing motor deficit due to MS in transgenic mice. This specific drug can re-myelinate damaged axons not only in MS patients but also in traumatic brain and spinal cord injury.

Ind-Cl stimulates ERβ, an oestrogen receptor. It is well known that high oestrogen levels have neuro-protective benefits, which improve MS symptoms. Thus pregnant women get almost complete relief from MS symptoms in their third trimesters, but following the child birth, MS symptoms return as the oestrogen levels plummet. Therefore oestrogen could be the key therapeutic molecule for MS, though high levels of oestrogen are linked to breast and uterine cancers and feminizing effects in men. But this unique ligand turns on ERβ without showing any negative effects of excessive oestrogen. It also inhibits selective inflammation of the central nervous system permanently. The researchers conducted electrophysiology tests to ensure the transmission of impulses by the re-myelinated axons.

To establish that remyelination, was due to the drug rather than immune response the researchers administered Ind-Cl in mice whose oligo-dendrocytes (cells responsible for remyelinating axons and myelin) were selectively low. They observed more efficient remyelination in such cases, thereby demonstrating that Ind-Cl works in two ways: indirectly through immune system by reducing brain and spinal cord inflammation, and directly by remyelinating axons. This makes Ind-Cl an extremely promising drug.

Moreover this compound can also work after the disease onset. An MS patient typically first visits the doctor when the axons have been severely affected and he or she has noticed some motor deficits, like loss of balance, inability to pick up an object, vision impairment. Ind-Cl can be administered at this point because it would not only prevent further damage but also help to reverse the symptoms. The researchers think that Ind-Cl can be developed for oral administration also, which is definitely an added advantage.

Several other Ind-Cl analogues could work even better at alleviating MS symptoms. The group has already identified four other analogues that would soon be tested on MS mice. They expect to select some of them for clinical trial also in near future.

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Arunima Maiti

Arunima Maiti

Biomedical scientist with special interest in reproductive biology.

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1 Response

  1. Avatar Lynne Heal says:

    If a cure was ever found many would have no jobs .We for years have needed a cure and this should of been found decades ago with billions donated ect

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