Dihexa Development - PubMed
Wright, Kawas, Harding/PubMed/2015
Why It Matters
This paper caught my attention because it describes a completely different approach to neurodegenerative diseases — not just slowing damage, but potentially growing new synaptic connections. The lead compound, Dihexa, works through a pathway (hepatocyte growth factor/c-Met) that's fundamentally different from current FDA-approved dementia drugs. That said, this is a 2015 review summarizing preclinical work, and I haven't seen widespread human trials emerge since then, which makes me wonder about translation challenges.
Key Findings
- Current FDA-approved Alzheimer's drugs (cholinesterase inhibitors and NMDA antagonists) do little to slow disease progression and don't address the underlying loss of neurons and synaptic connections
- The brain renin-angiotensin system, particularly angiotensin IV binding to AT4 receptors, appears to play a role in learning, memory, and motor function
- There's scientific controversy about what the AT4 receptor actually is — some evidence points to IRAP (insulin-regulated aminopeptidase), while the authors' lab suggests it's the hepatocyte growth factor/c-Met receptor system
- The research team synthesized angiotensin IV-based small molecules that are metabolically stable, cross the blood-brain barrier, and improve memory and motor function in animal models
- The lead compound Dihexa shows potential for overcoming memory and motor dysfunction by increasing synaptic connectivity through formation of new functional synapses
Read the Paper↗PMID: 25455861