Tropical Myeloneuropathies Medication

Updated: Apr 13, 2021
  • Author: Emad R Noor, MBChB; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
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Medication

Medication Summary

HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP)

A multicenter, randomized, double-blind study in 48 patients indicated that treatment with subcutaneous interferon alfa (Roferon) 3 million U (MU) twice a week was effective in more than 66.7%. [18] In another study, 32 patients were treated with interferon alfa; 20 patients showed a fair-to-excellent response in motor function. The effect was sustained, however, for only 1-3 months after the last injection. [16]

An open-label study showed that pentoxifylline 300 mg PO once a day induced clinical improvement in 14 of 15 patients. The authors postulated that the effect probably was due to TNF-alpha suppression. [19] In one open-label trial, 12 patients with HAM/TSP were treated with doses of interferon beta-1a of up to 60 µg twice weekly. During the trial, the therapy reduced the HTLV-1 tax messenger RNA load, but the HTLV-1 proviral DNA load remained unchanged. Some measures of motor function were improved, and no significant clinical progression occurred during therapy. [20]

A cross-sectional study of 13 patients treated with triple therapy of peg interferon (INF) as an immunomodulator, sodium valproate as a deacetylase inhibitor, and methylprednisolone as an anti-inflammatory agent showed marked improvement in spasticity and disability after 6 months of treatment. [21]

Mogamulizumab is a humanized anti-CCR4 monoclonal antibody that targets infected cells in patients with HAM/TSP. It was evaluated in an uncontrolled phase 1 and phase 2a trial in Japan, results of which showed a decrease in the number of HTLV-1-infected cells and inflammatory markers. Studies are still needed to demonstrate clinical efficacy of this medication. [22]

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Interferons

Class Summary

These agents are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions.

Interferon beta-1a (Avonex, Rebif)

For treatment of relapsing remitting MS. Avonex has also gained approval for treating patients with a first MS attack if brain MRI shows abnormalities characteristic of MS. Believed to act via ability to counteract cell surface expression of proinflammatory or pro-adhesion molecules on immune cells, among other effects. More studies needed to fully understand mechanisms of action. Only differs from interferon beta-1b in that it has amino acid sequence identical to that of natural compound and is glycosylated. Presence of glycosylation may lead to structural stability and presumably to higher biological potency.

Interferons act through common receptor that activates Jak/Stat pathway of signal transduction molecules, which, in turn, lead to activation of interferon-responsive genes. Interferon beta may decrease expression of B7-1 (a proinflammatory molecule) on surface of immune cells and increase levels of TGF-beta (anti-inflammatory) in circulation of MS patients. Interferon beta-1a is most convenient ABC drug to administer due to weekly schedule.

Peginterferon alfa 2a (Pegasys)

PEG-IFN alfa-2a consists of IFN alfa-2a attached to a 40-kd branched PEG molecule. Clinical and immunological improvements reported with use. It is predominantly metabolized by the liver. Used in combination with sodium valproate and prednisolone. 

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Blood viscosity reducer agents

Class Summary

These agents decrease the viscosity of blood.

Pentoxifylline (Trental)

May alter rheology of red blood cells, which, in turn, reduces blood viscosity

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Corticosteroids

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body’s immune response to diverse stimuli.

Prednisolone (Orapred, Millipred)

Prednisolone inhibits inflammatory reactions associated with the disease by suppressing key components of the immune system. Administered in combination with valproate sodium and peginterferon alfa 2a. 

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Histone diacetylase inhibitors

Class Summary

Agents that are histone deacetylase inhibitors may improve clinical aspects of the disease. 

Valproic acid (Depakote, Depakote ER, Depakote Sprinkles

Sodium valproate, as a histone deacetylase inhibitor, has positive effects on the reduction of proviral load (PVL) and improves recognition of infected cells by the immune system. Administered in combination with peginterferon alfa 2a and prednisolone. 

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CCR4 Inhibitors

Class Summary

Monoclonal antibodies in this class may cause target cell depletion by binding to CCR4 target cells. 

Mogamulizumab (Mogamulizumab-kpkc, Poteligeo)

This anti-CCR4 antibody selectively targets and therefore reduces the number of HTLV1 infected cells. It also decreases the inflammatory markers in CSF, which may be associated with the efficacy of this drug. Side effects include rash, leukopenia, and lymphopenia. This was a phase 1-2a trial. A longer-term safety trial is being performed to obtain additional data on the safety of the medication. Further trials will be needed to assess the clinical efficacy of the drug

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