Excerpt from patent application:
Inventors: Øystein Fluge & Olav Mella
Date of publication 26 11 2014
Nitric oxide donor for the treatment of chronic fatigue syndrome.
Description
[0001] The present invention relates in a first aspect to a nitric oxide donor for use in the treatment of chronic fatigue syndrome also known as myalgic encyphalomyelitis.
In particular, the present invention relates to the use of a pharmaceutical composition containing a nitric oxide donor for the treatment of chronic fatigue syndrome/myalgic encyphalomyelitis in a subject afflicted with said disease.
In a further aspect, the present invention relates to a combination of a nitric oxide donor with a B-cell depleting agent for use in the treatment of chronic fatigue syndrome.
Said combination may be provided in form of a kit comprising pharmaceutically effective dosages of said compounds. Further, the present invention relates to a method for treating chronic fatigue syndrome comprising the step of administering a nitric oxide donor to a subject afflicted therewith.
Brief description of the present invention
[0018] In a first aspect, the present invention relates to the use of a nitric oxide donor (NO donor) for use in the treatment of chronic fatigue syndrome (CFS).
[0019] That is, the present inventors recognized that administration of a NO donor relieve the symptoms of CFS and, thus, may be useful in the treatment of chronic fatigue syndrome.
[0020] In particular, the present inventors recognized that an immediate relief after administration of an NO donor can be observed. In contrast to medication administered so far for treatment of CFS, which are characterized by a remarkable lag time of treatment success, as described for example for the treatment with Rituximab or Methotrexate, see e.g. WO 2009/083602. Thus, the administration of a NO donor surprisingly allow a treatment of CFS patients for immediate relief of symptoms without any delay as described for e.g. a B-cell depleting agent, like Rituximab, before.
An alternative strategy was applied, using supplement with relatively high doses of L-Arginine 5 g twice daily combined with L-Citrulline 200 mg twice daily. L-Arginine is the sole substrate of Nitric Oxide Synthases (NOS), thus this approach aims to overcome the dysregulated nitric oxide system in CFS/ME patients by providing relatively high doses of the substrate.
[0021] Further, the skilled person is well aware of other compounds suitable to influence the NO level, e.g. by influencing the amount or level of available substrate for NO production. Examples thereof include compounds inhibiting arginase, e.g. arginase II, a competitor of the NO synthase (NOS). Other examples comprise compounds stimulating the activity of NO synthase, in particular, of the eNOS, either by increasing the amount or level of NOS or the turn over rate of the enzyme. These compounds may act directly or indirectly through affecting the level of natural eNOS stimulators, like
sphinogine 1-phospate.
[0022] Hence, in another aspect, the present invention relates to a pharmaceutical composition comprising a NO donor optionally in combination with a pharmaceutically acceptable diluents, excipient or carrier for use in the treatment a chronic fatigue syndrome.
[0023] Moreover a composition is provided containing a combination of a nitric oxide donor and a B-cell depleting agent. Said composition is particular useful in form of a pharmaceutical composition for use in the treatment of chronic
fatigue syndrome. That is, while an immediate relief is obtained with the first component, the NO donor, a delayed response is obtained by the treatment with the B-cell depleting agent, as described in the art. Hence, it is desired to
administer the pharmaceutical composition containing the combination of NO donor and B-cell depleting agent in a combination, either simultaneously, separately, or sequentially.
[0024] Furthermore, the present invention provides a kit comprising as a first component a NO donor and as a second component a B-cell depleting agent. Said kit is useful in the treatment of chronic fatigue syndrome.
[0025] Finally, the present invention provides methods for treating chronic fatigue syndrome comprising the step of administering daily a nitric oxide donor. Preferably, said method of treatment includes the combinatorial treatment with
a B-cell depleting agent.
