Treatment of dementia
The invention describes improved treatments for Frontotemporal dementia based on the use of a methylthioninium compound in combination with a compound which directly modifies synaptic neurotransmission in the brain, such as a symptomatic Alzheimer's disease treatment (e.g. acetylcholinesterase and/or memantine).
1. A method of treatment of an FTLD syndrome in a human subject, which method comprises administering to said subject:
a first compound which is a methylthioninium (MT) compound in combination with
a second compound, which second compound directly modifies synaptic neurotransmission in the brain,
wherein the FTLD syndrome is selected from behavioral-variant frontotemporal dementia, primary progressive aphasia, and semantic dementia; and wherein the MT compound is a salt of:
or a hydrate or solvate thereof, and
wherein the second compound is either an acetylcholinesterase inhibitor or an NMDA receptor antagonist.
2. A method claim 1 , wherein either:
(a) the MT compound and the neurotransmission modifying compound are administered sequentially within 12 hours of each other;
(b) the subject is pre-treated with the neurotransmission modifying compound prior to commencement of the treatment with the MT compound; or
(c) the MT compound and the neurotransmission modifying compound are administered simultaneously, optionally within a single dosage unit.
3. A method as claimed in claim 1 , wherein the MT compound is an LMTX compound of the following formula:
wherein each of H n A and H n B (where present) are protic acids which may be the same or different,
and wherein p=1 or 2; q=0 or 1; n=1 or 2; (p+q)×n=2.
4. A method as claimed in claim 3 , wherein the MT compound has the following formula:
wherein each of H n X is a protic acid.
5. A method as claimed in claim 3 , wherein the MT compound has the following formula and H 2 A is a di-protic acid:
6. A method as claimed in claim 4 , wherein the MT compound has the following formula and is a bis-monoprotic acid:
7. A method as claimed in claim 3 , wherein the or each protic acid is an inorganic acid.
8. A method as claimed in claim 3 , wherein the or each protic acid is an organic acid.
9. A method as claimed in claim 8 , wherein the MT compound is LMTM:
10. A method as claimed in claim 1 , wherein the FTLD syndrome is FTLD with tau pathology or FTLD with TAR DNA-binding protein 43 pathology.
11. A method as claimed in claim 1 , wherein the total daily dose of MT provided by the MT compound is from around any of 1 to 350 mg; 2 to 300 mg; 4 to 250 mg; 6 to 240 mg; 7 to 220 mg, or 3 to 70 mg.
12. A method as claimed in claim 1 , wherein the total daily dose of MT provided by the MT compound is from around any of 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4 mg to around any of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 mg.