This Is MS Multiple Sclerosis Community: Knowledge & Support

I include this preclinical abstract because the substance being tested is a voltage-gated potassium channel modulator. I think this strategy could be promising to provide neuroprotection, and this is the first oral drug I've seen in the preclinical stage that goes after Kv1.3 (1.3 is the channel of interest for MS).



BNC-245 – a novel compound for multiple sclerosis treatment

E. Andriambeloson, S. Wagner, L. Gorj, J. Bindler, J. Mould, B. Flynn (Illkirch, F; Adelaide, AUS)

The Kv1.3 ion channel modulates the function of autoreactive effector memory T-cells (TEM) which have been implicated in the pathogenesis of autoimmune diseases such multiple sclerosis (MS) and rheumatoid arthritis.

Under whole cell patch clamp conditions, BNC-245 exhibits 5 fold selectivity for Kv1.3 over Kv1.1 or Kv1.5 channels with an IC50 of 75 nM. Consistent with the role of Kv1.3 in T cell activation, BNC-245 reduces the proliferation of MBP- activated memory T cells in a dose dependent manner. Pharmacokinetic studies indicate that BNC-245 has good drug like properties with an oral bioavailability of 90% and a half life of 5 hr.
In the present study, we demonstrate in-vivo efficacy of BNC-245, a novel Kv1.3 channel blocker, in ovalbumin -induced delayed type hypersensitivity (DTH) and myelin basic protein (MBP) –induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats.
BNC-245 administered PO as a single dose on the day of albumin challenge, significantly reduced the DTH response in rats in a dose-dependent manner with a minimum effective dose <= 0.1 mg/kg. In EAE-rats, BNC-245 (30 mg/kg/d) administered from days 8 to 12 post-MBP significantly reduced the severity of the disease (area under curve reduced to 56% of control).

Together, these results indicate that BNC-245 modulates TEM function and attenuates neurological deficits in a rat model of MS, most probably via inhibition of Kv1.3 K+ channels. BNC-245 could therefore provide a novel for treatment for MS and other autoimmune diseases.

ECTRIMS link

Dignan


I agree with you about the potential for neuroprotection and since I'm on a progesterone roll let's not forget that it also impacts the Kv1.3 potassium channel.

A nongenomic mechanism for progesterone-mediated immunosuppression: inhibition of K+ channels, Ca2+ signaling, and gene expression in T lymphocytes

It's available orally (compounded) and in a cream too.

Thanks for posting the abstract and info. It's nice to know they're pursuing the potassium channel angle. In the interim, I'm sticking with progesterone.

Sharon

_________________
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,