Granted Patent B2

US 12,636,264 · App. 17/802,908 · Granted May 26, 2026

Inventors: Zixu Zhou (San Diego, CA); Qiuyang Wu (San Diego, CA); Sheng Zhong (San Diego, CA); Zhangming Yan (San Diego, CA)

Assignee: Genemo, Inc.

A61K31/13A61P25/28

Abstract

Claims (35)

1 . A method of managing, or treating a neuronal disorder associated with neuro-excitotoxicity in a subject, comprising

(a) monitoring the expression level of phosphoglycerate dehydrogenase (PHGDH) in the subject over an observation period of time; and

(b) administering to the subject an effective amount of a therapy for managing or treating the neuronal disorder, if the expression level of PHGDH is increased during the observation period;

wherein the neuronal disorder is managed or treated in the subject, and the monitoring further comprises:

providing a series of samples taken from the subject at sequential time points before or during the observation period;

measuring the expression level of PHGDH using the series of samples; and

determining a longitudinal trend in the expression level of PHGDH.

2 . The method of claim 1 , wherein the therapy comprises at least one NMDA receptor antagonist.

3 . The method of claim 2 , wherein the NMDA receptor antagonist is memantine.

4 . The method of claim 1 , wherein the therapy comprises at least one agent inhibiting in vivo production of glycine and/or serine in the subject.

5 . The method of claim 4 , wherein the agent inhibiting in vivo production of glycine and/or serine is a PHGDH inhibitor.

6 . The method of claim 1 , wherein the therapy comprises at least one agent inhibiting in vivo transportation of glycine and/or serine to excitatory synapses in the subject.

7 . The method of claim 1 , further comprising

(c) extending the observation period for an extended period, if the expression level of PHGDH is not increased during the observation period; optionally wherein the extended period is at least 1 month; optionally wherein the method further comprises measuring the expression level every 6 months during the extended period.

8 . The method of claim 1 , wherein the observation period is at least 1 month.

9 . The method of claim 1 , wherein the subject is asymptomatic of the neuronal disorder at the beginning or during the observation period.

10 . A method of managing or treating a neuronal disorder associated with neuro-excitotoxicity in a subject who is under an ongoing first therapy for the neuronal disorder, comprising

(a) monitoring the expression level of phosphoglycerate dehydrogenase (PHGDH) in the subject over an observation period of time;

(b) administering a second therapy to the subject, if the expression level of PHGDH is increased during the observation period; wherein the first therapy and second therapy are different; and

(c) ceasing the ongoing first therapy and administering a third therapy to the subject, if the expression level of PHGDH is not increased during the observation period;

wherein the neuronal disorder is managed or treated in the subject, the first therapy comprises at least one NMDA receptor antagonist, and the third therapy does not comprise any NMDA receptor antagonist.

11 . The method of claim 10 , wherein the step (c) selected from (ii) further comprises extending the observation period for an extended period.

12 . A method of diagnosing a neuronal disorder associated with neuro-excitotoxicity in a subject, comprising

(a) monitoring the expression level of phosphoglycerate dehydrogenase (PHGDH) in the subject over an observation period of time; and

(b) classifying the subject as having the neuronal disorder or at a high risk of developing the neuronal disorder, if the expression level of PHGDH is increased during the observation period; or

(c) classifying the subject as having a low risk of developing the neuronal disorder, if the expression level of PHGDH is increased during the observation period;

wherein the neuronal disorder is diagnosed in the subject, monitoring the expression level of PHGDH is performed by measuring the amount of extracellular RNA (exRNA) produced from expression of PHGDH in the subject, and the exRNA is produced from transcription of the PHGDH gene.

13 . The method of claim 12 ,

wherein the risk is a risk of developing the neuronal disorder in less than 5 years, or

the risk is a risk of having the onset of symptom for the neuronal disorder-in less than.

14 . The method of claim 1 , wherein

(a) at least one of the series of samples is (i) a sample preserved from a time point before the observation period; (ii) a whole blood sample, a plasma sample, a serum sample, a saliva sample, a cell culture media sample, a urine sample, an amniotic fluid sample, a mucus sample, a semen sample, a vaginal fluid sample, a sputum sample, a cerebrospinal fluid sample, a lymphatic fluid sample, an ocular fluid sample, a sweat sample, or a stool sample; or (iii) has a liquid volume of less than or equal to about 100 μl, about 50 μl, about 5 μl, or about 1 μl; and

(b) extending the observation period comprises taking at least one additional sample from the subject and measuring expression level of PHGDH using said sample.

15 . The method of claim 1 , wherein the neuro-excitotoxicity is resulted from overexcitation of an excitatory synaptic receptor upon binding of glycine and/or serine to the excitatory synaptic receptor.

16 . The method of claim 1 , wherein the neuronal disorder is Alzheimer's disease, schizophrenia, ALS, epilepsy, or drug addiction.

Assignments (1)

Continuity (2)

References Cited (108)