Sema4D Modulation of GABAergic Synapse Density
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Solution Overview
Problem
Current understanding of GABAergic synapse formation and regulation is limited, particularly in the context of neurological disorders like epilepsy, where increasing inhibitory synapses could help modulate neuronal activity, but effective molecular mechanisms and therapeutic agents are not well established.
Innovation Solution
Modulating GABAergic synapses by contacting neurons with PlexinB agonists or Sema4D polypeptides, or their nucleic acid molecules, to promote or inhibit synapse formation, thereby regulating neuronal activity and treating neurological disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If Sema4D is knocked down in postsynaptic neurons, then GABAergic synapse density decreases, but glutamatergic synapse density remains unaffected
Solution Approach 1:
The patent applies local quality by using Sema4D-specific antibodies that selectively bind to and modulate Sema4D protein at GABAergic synapses without affecting other synapse types. This localized, molecule-specific approach enables selective regulation of GABAergic synapse density while leaving glutamatergic synapses unchanged, resolving the contradiction between quantity control and selectivity.
2Quantity of substance
If Sema4D is constitutively deleted, then GABAergic synapse development is deficient, but immune system function is also impaired
Solution Approach 1:
The patent extracts and isolates the specific function of Sema4D in GABAergic synapse formation by using targeted antibodies that bind only to Sema4D at neuronal synapses. This extraction approach allows selective modulation of synaptic function without globally deleting the Sema4D gene, thereby preserving immune system functions that depend on intact Sema4D while still achieving the desired effect on GABAergic synapse density.
3Adaptability or versatility
If more molecules are identified to regulate GABAergic synapses, then therapeutic options increase, but molecular mechanism complexity increases
Solution Approach 1:
The patent demonstrates universality by showing that a single molecule, Sema4D, can serve multiple functions: it regulates GABAergic synapse formation, influences neuronal development, and potentially affects immune responses. By focusing on this multi-functional molecule rather than identifying numerous separate molecules, the patent increases therapeutic options while avoiding the complexity of multiple molecular pathways.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach effectively increases GABAergic synapse density and modulates neuronal activity, potentially addressing the development and progression of epilepsy and other neurological disorders by enhancing inhibitory control.
Implementation Method 1
contacting at least one of the neurons with a PlexinB receptor agonist or a nucleic acid molecule encoding a PlexinB agonist or a PlexinB polypeptide
Data Source
AI summary
The present technology relates to methods of modulating the number of GABAergic synapses between at least two neurons. These methods include contacting at least one of the neurons with a PlexinB agonist or a nucleic acid molecule encoding a PlexinB agonist, such as a composition including a Sema4D polypeptide or an extracellular fragment thereof, or a nucleic acid molecule encoding the Sema4D polypeptide or extracellular fragment thereof. The present technology also relates to methods of modulating neuronal activity in the central nervous system or peripheral nervous system of a subject in need thereof by modulating the number of GABAergic synapses between at least two neurons. The present technology further relates to methods of treating a neurological disorder that would benefit from modulating neuronal activity in the central nervous system or peripheral nervous system of a subject in need thereof.