University of Eastern Finland identifies vitamin transporter protein for brain drug delivery

Researchers at the University of Eastern Finland, led by Associate Professor Kristiina Huttunen, identified that the sodium-dependent multivitamin transporter (SMVT) can deliver creatine-derived prodrugs across the blood-brain barrier and into neurons. Published in ACS Chemical Neuroscience, the findings offer a potential therapeutic route for Creatine Transporter Deficiency Syndrome, an untreatable disorder affecting 1 in 100,000 boys.

SMVT function and brain delivery mechanism

• ▪Researchers at the University of Eastern Finland identified that the sodium-dependent multivitamin transporter (SMVT) can transport creatine-derived prodrugs across the blood-brain barrier and into neurons.
• ▪The sodium-dependent multivitamin transporter (SMVT) is encoded by the SLC5A6 gene and naturally transports biotin, pantothenic acid, and alpha-lipoic acid across blood capillary endothelial cells into the brain.
• ▪University of Eastern Finland researchers modified creatine chemically by attaching structural features recognized by SMVT, creating prodrug versions that release active creatine inside neuronal cells.

Creatine Transporter Deficiency Syndrome and SMVT

• ▪Oral creatine supplementation fails to treat Creatine Transporter Deficiency Syndrome because ingested creatine cannot cross into the brain without a functional CRT1 transporter.
• ▪Creatine Transporter Deficiency Syndrome (CTDS) is a rare X-linked neurological disorder affecting approximately 1 in 100,000 boys, caused by SLC6A8 gene mutations that impair the primary creatine importer CRT1.
• ▪Because SMVT belongs to the SLC5 gene family while CRT1 belongs to the SLC6 family, SMVT remains functional in patients with Creatine Transporter Deficiency Syndrome.

The blood-brain barrier and transport targeting

• ▪The blood-brain barrier prevents many therapeutic drug compounds from entering the central nervous system.
• ▪Researchers led by Associate Professor Kristiina Huttunen targeted transport systems naturally present in the blood-brain barrier, such as SMVT, to deliver therapeutic compounds instead of bypassing the barrier.