ANAVEX2-73 for the treatment of genetic neurodevelopmental disorders
The present invention provides methods for treating a genetic neurodevelopmental disorder, such as Rett syndrome or Fragile X-syndrome, comprising evaluating a subject for his/her occurrence and/or severity of symptoms and/or specific biomarker levels before administering a dosage formulation of ANAVEX2-73 to the subject, administering the dosage formulation of ANAVEX2-73 to the subject for a period of time, re-evaluating the occurrence and/or severity of symptoms and/or specific biomarker levels, and optionally modifying the dosage of ANAVEX2-73 administered to the subject based on the re-evaluation results.
1 . A method for treating Fragile X Syndrome in a subject in need thereof, the method comprising:
(a) evaluating the subject for the occurrence and/or severity of one or more Fragile X Syndrome symptoms selected from the group consisting of: cognitive impairment, motor learning impairment, balance impairment, muscular strength impairment, seizures, sleep dysfunction, breathing impairment, and anxiety;
(b) measuring a baseline level of at least one biomarker in the subject to determine a baseline biomarker level, wherein the biomarker is selected from plasma glutamate, PI3K, pAkt, mTOR, pMAPK, pERK, and any combination thereof;
(c) daily administering to the subject a dosage formulation comprising a therapeutically effective amount of tetrahydro-N, N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73) for a period of at least about 1 week, wherein the dosage formulation is selected from a liquid oral dosage formulation, a topical formulation, a transmucosal formulation, a transdermal formulation, a buccal formulation, a sublingual formulation, and a parental formulation;
(d) re-evaluating the subject for the occurrence and/or severity of the symptoms evaluated in (a), evaluating the subject for the occurrence of adverse events; and measuring the biomarker level in the subject to determine a second biomarker level and comparing the second biomarker level to the baseline biomarker level; and
(e) optionally modifying the dosage of ANAVEX2-73 administered to the subject based on the re-evaluations in (d) and the second biomarker level in (d), wherein absence of improvement in at least one symptom indicates optionally increasing the dosage of ANAVEX2-73, occurrence of an adverse event indicates decreasing the dosage of ANAVEX2-73, and the second biomarker level about the same or higher than the baseline biomarker level indicates optionally increasing the dosage of ANAVEX2-73.
2 . The method of claim 1 , wherein the amount of ANAVEX2-73 is from about 0.2 mg to about 40 mg.
3 . The method of claim 1 , wherein the dosage formulation comprises ANAVEX2-73 at a concentration of about 0.2 mg/ml to about 8 mg/ml.
4 . The method of claim 1 , wherein the dosage formulation is a liquid oral dosage formulation comprising about 0.2 mg to about 40 mg of ANAVEX2-73, and at least one of a preservative and a flavoring agent.
5 . The method of claim 1 , wherein the therapeutically effective amount of ANAVEX2-73 is administered in at least one dose of the liquid dosage formulation, at least once daily.
6 . The method of claim 1 , wherein the at least one biomarker is selected from pAKt and pERK.
7 . The method of claim 6 , wherein at least two biomarkers are selected, and the at least two biomarkers are pAKt and pERK.