Animals got it wrong again or is a fluke?

A

Imatinib is a small molecule kinase inhibitor used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec (USA) or Glivec (Europe/Australia) as its mesylate salt, imatinib mesilate (INN). It is occasionally referred to as CGP57148B or STI571 (especially in older

Tyrphostin AG490, a tyrosine kinase inhibitor, blocks actively induced experimental autoimmune encephalomyelitis.Constantin G, Brocke S, Izikson A, Laudanna C, Butcher EC. Eur J Immunol. 1998 Nov;28(11):3523-9

The selective M-CSF receptor tyrosine kinase inhibitor Ki20227 suppresses experimental autoimmune encephalomyelitis. Uemura Y, Ohno H, Ohzeki Y, Takanashi H, Murooka H, Kubo K, Serizawa I. J Neuroimmunol. 2008 Mar;195(1-2):73-80.

Effects of imatinib mesylate in mouse models of multiple sclerosis and in vitro determinants. Azizi G, Haidari MR, Khorramizadeh M, Naddafi F,Sadria R, Javanbakht MH, Sedaghat R, Tofighi Zavareh F, Mirshafiey A. Iran J Allergy Asthma Immunol. 2014 Jun;13(3):198-206.

CNS demyelination after initiating the tyrosine kinase inhibitor imatinib: A report of two cases. Rotstein DL, Sawicka K, Bharatha A, Montalban X, Lipton JH. Mult Scler. 2019 Dec 17:1352458519892914.

The tyrosine kinase inhibitor, imatinib, used to treat certain malignancies, is in clinical trials as a potential treatment for multiple sclerosis and acute stroke. This is the first report of cases of multifocal central nervous system (CNS) demyelination following exposure to imatinib. One case was severe with bilateral optic neuritis and transverse myelitis that was AQP4 IgG and myelin oligodendrocyte glycoprotein (MOG) IgG negative and improved after plasma exchange and withdrawal of imatinib. The second case involved a unilateral optic neuritis with magnetic resonance imaging (MRI) brain confirming other demyelinating lesions. Although the mechanism is unknown, demyelination on imatinib could be related to activation of previously normal T-cells.

There is an ongoing trial of 200 pwMS (NCT03674099)

Have animals got it wrong ….again

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