Sage发现潜在药物分子可治疗多种CNS紊乱

最近来自美国坎布里奇的Sage医药公司研究人员表示他们发现一种潜在机制能间接影响人体中枢神经系统。这种新发现的分子24(S)-HC可以通过影响NMDA受体来影响人类的中枢神经系统并进而对人类的学习、记忆和社会活动起作用。研究人员表示，此前在治疗中枢神经系统紊乱（CNS disorder）的一大难点在于由不同疾病导致的CNS disorder机制各不相同。此次Sage公司的发现可能为治疗该类疾病开辟新道路。

详细英文报道：

Scientists at the Cambridge, MA, startup Sage Therapeutics have discovered an innate mechanism that indirectly influences a key receptor linked to a number of neurologic and psychiatric disorders, including Alzheimer's, schizophrenia, autism and depression.

The newly discovered natural allosteric modulator influences the N-methyl-D-aspartate (NMDA) receptor, which is known to play a role in regulating synaptic function in the central nervous system and impact human learning, memory and social behaviors.

"One of the difficulties in treating CNS disorders is that these diseases are heterogeneous," Sage CEO Jeffrey Jonas told FierceBiotech Research in an interview, referring to the diverse nature of neuropsychiatric disorders.

Working with collaborators at Weill Cornell Medical College and Washington University School of Medicine in St. Louis, the Sage team screened a series of compounds to identify 24(S)-hydroxycholesterol (24(S)-HC), a brain-specific metabolite of cholesterol, as a potent and selective positive allosteric modulator of NMDA receptor function. In preclinical studies, treatment with Sage's SGE-301, a synthetic version of (24(S)-HC), showed a reversal in cognitive and social deficits related to the NMDA receptor in rats.

Jonas said the allosteric modulator SGE-301 essentially acts like ketamine but without the safety issues associated with it. Ketamine, an anesthetic that has been abused as the party drug known as "Special K," also works on the NMDA receptor--evidence of its effectiveness as a fast antidepressant.

The research, published Oct. 30 in the Journal of Neuroscience, advances Sage's Positive and Negative Allosteric Modulator (PANAM) platform, aimed at treating CNS and orphan diseases.

Sage is funded by Third Rock Ventures and Arch Ventures and has so far received $58 million in venture cash plus a $10 million grant from the NIH to work on fragile X syndrome.