Treatment of diseases related to hyperactivity of the complement system
Raising the level of Factor I above physiological levels can be used to treat diseases in which the underlying pathology is linked to overactivity of the C3b-feedback cycle and the generation and pro-inflammatory effects of iC3b. Methods, agents, and compositions for treatment of such diseases are described.
1. A method for treating Age-related Macular Degeneration (AMD) or atypical Hemolytic Uremic Syndrome (aHUS) in a human subject which comprises lowering the amount of C3b activity in a subject, the method comprising:
administering a pharmaceutical composition comprising a therapeutically effective amount of an agent selected from native Factor I and a polypeptide that has at least 90% amino acid identity with native Factor I and that retains C3b-inactivating activity and iC3b degrading activity, and does not comprise Factor H, to the human subject;
wherein administration of the pharmaceutical composition increases the level of C3b-inactivating activity and iC3b degrading activity in the human subject to a level that exceeds a normal level of C3b-inactivating activity and iC3b degrading activity in the human subject;
thereby treating AMD or aHUS in the human subject.
2. The method according to claim 1 , wherein the level of C3b-inactivating activity and iC3b degrading activity is increased by at least 10% above the normal level.
3. The method according to claim 1 , wherein the level of C3b-inactivating activity and iC3b degrading activity is increased by no more than 50% above the normal level.
4. The method according to claim 1 , wherein the subject has a normal level of C3b-inactivating activity and iC3b degrading activity prior to increasing the level of C3b-inactivating activity and iC3b degrading activity in the subject.
5. The method according to claim 1 , wherein the level of C3b-inactivating activity and iC3b degrading activity in an eye of the subject is increased to a level that exceeds a normal level of C3b-inactivating activity and iC3b degrading activity in an eye of the subject.